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Presents an abstract of a paper that focuses on electron cyclotron emission (ECE) imaging of electron temperature profiles and fluctuations. Reasons why ECE is a powerful diagnostic in a high performance/high magnetic field, magnetic confinement experiment; Description of the device.

Recent years have seen the creation and popularization of various complex in vitro models (CIVMs), such as organoids and organs-on-chip, as a technology with the potential to reduce animal usage in pharma while also enhancing our ability to create safe and efficacious drugs for patients. Public awareness of CIVMs has increased, in part, due to the recent passage of the FDA Modernization Act 2.0. This visibility is expected to spur deeper investment in and adoption of such models. Thus, end-users and model developers alike require a framework to both understand the readiness of current models to enter the drug development process, and to assess upcoming models for the same. This review presents such a framework for model selection based on comparative -omics data (which we term model-omics), and metrics for qualification of specific test assays that a model may support that we term context-of-use (COU) assays. We surveyed existing healthy tissue models and assays for ten drug development-critical organs of the body, and provide evaluations of readiness and suggestions for improving model-omics and COU assays for each. In whole, this review comes from a pharma perspective, and seeks to provide an evaluation of where CIVMs are poised for maximum impact in the drug development process, and a roadmap for realizing that potential., (Creative Commons Attribution license.)

Background: There are limited data on sex-specific outcomes and management of cardiogenic shock complicating ST-segment elevation myocardial infarction (CS-STEMI). We investigated whether any sex bias exists in the admission to revascularization capable hospitals (RCH) or intensive cardiac care units (ICCU) and its impact on in-hospital mortality., Methods: We used the Spanish National Health System Minimum Basic Data from 2003 to 2015 to identify patients with CS-STEMI. The primary outcome was sex differences in in-hospital mortality., Results: Among 340 490 STEMI patients, 20 262 (6%) had CS and 29.2% were female. CS incidence was higher in women than in men (7.9% vs 5.1%, P = .001). Women were older and had more hypertension and diabetes, and were less often admitted to RCH than men (from 58.7% in 2003 to 79.6% in 2015; and from 61.9% in 2003 to 85.3% in 2015; respectively, P = .01), and to ICCU centres (25.7% vs 29.2%, P = .001). Adjusted mortality was higher in women than men over time (from 79.5 ± 4.3% to 65.8 ± 6.5%; and from 67.8 ± 6% to 58.1 ± 6.5%; respectively, P < .001). ICCU availability was associated with higher use of Percutaneous coronary intervention (PCI) in women (46.8% to 67.2%; P < .001) but was even higher in men (54.8% to 77.4%; P < .001). In ICCU centres, adjusted mortality rates decreased in both sexes, but lower in women (from 74.9 ± 5.4% to 66.3 ± 6.6%) than in men (from 67.8 ± 6.0% to 58.1 ± 6.5%, P < .001). Female sex was an independent predictor of mortality (OR 1.18 95% CI 1.10-1.27, P < .001)., Conclusions: Women with CS-STEMI were less referred to tertiary-care centres and had a higher adjusted in-hospital mortality than men., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

The family Chlamydiaceae currently comprises a single genus Chlamydia, with 11 validly published species and seven more taxa. It includes the human pathogens Chlamydia (C.) trachomatis, C. pneumoniae and C. psittaci, a zoonotic agent causing avian chlamydiosis and human psittacosis, as well as other proven or potential pathogens in ruminants, birds, snakes, reptiles and turtles. During routine testing of 15 apparently healthy captive flamingos in a zoo in 2011, an atypical strain of Chlamydiaceae was detected by real-time PCR of cloacal swab samples. Sequence analysis of the 16S rRNA gene revealed high similarity to the uncultured Chlamydiales bacterium clone 122, which previously had been found in gulls. As more samples were collected during annual campaigns of the flamingo ringing program in southern France from 2012 to 2015, Chlamydiaceae-specific DNA was detected by PCR in 30.9% of wild birds. From these samples, three strains were successfully grown in cell culture. Ultrastructural analysis, comparison of 16S and 23S rRNA gene sequences, whole-genome analysis based on de novo hybrid-assembled sequences of the new strains as well as subsequent calculation of taxonomic parameters revealed that the relatedness of the flamingo isolates to established members of the family Chlamydiaceae was sufficiently distant to indicate that the three strains belong to two distinct species within a new genus. Based on these data, we propose the introduction of Chlamydiifrater gen. nov., as a new genus, and Chlamydiifrater phoenicopteri sp. nov. and Chlamydiifrater volucris sp. nov., as two new species of the genus., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Chlamydiaceae are obligate intracellular bacterial pathogens for humans and animals. A recent study highlighted that a Chlamydiaceae intermediary between C. psittaci and C. abortus can infect hawks. Here, an isolate was obtained upon passage of cloacal and conjunctival sac material collected from a female hatch-year red-shouldered hawk (Buteo lineatus) in cultured cells. The diseased bird, one of 12 birds housed in a rehabilitation center, developed conjunctivitis and later died. Swabs from both sites tested positive for Chlamydia using the QuickVue Chlamydia test. The isolate, named RSHA, tested negative in qPCR assays specific for C. psittaci and C. abortus, respectively. Analysis of the 16S rRNA, 23S rRNA and whole genome sequences as well as MLST, ANIb and TETRA values reveal that C. psittaci and C. abortus are the closest relatives of RSHA. However, the overall results strongly suggest a phylogenetic intermediate position between these two species. Therefore, we propose the introduction of a new species designated Chlamydia buteonis with RSHA T as the type strain., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Importance: Monitoring emergency care quality requires understanding which conditions benefit most from timely, quality emergency care., Objectives: To identify a set of emergency care-sensitive conditions (ECSCs) that are treated in most emergency departments (EDs), are associated with a spectrum of adult age groups, and represent common reasons for seeking emergency care and to provide benchmark national estimates of ECSC acute care utilization., Design, Setting, and Participants: A modified Delphi method was used to identify ECSCs. In a cross-sectional analysis, ECSC-associated visits by adults (aged ≥18 years) were identified based on International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes and analyzed with nationally representative data from the 2016 US Nationwide Emergency Department Sample. Data analysis was conducted from January 2018 to December 2018., Main Outcomes and Measures: Identification of ECSCs and ECSC-associated ED utilization patterns, length of stay, and charges., Results: An expert panel rated 51 condition groups as emergency care sensitive. Emergency care-sensitive conditions represented 16 033 359 of 114 323 044 ED visits (14.0%) in 2016. On average, 8 535 261 of 17 886 220 ED admissions (47.7%) were attributed to ECSCs. The most common ECSC ED visits were for sepsis (1 716 004 [10.7%]), chronic obstructive pulmonary disease (1 273 319 [7.9%]), pneumonia (1 263 971 [7.9%]), asthma (970 829 [6.1%]), and heart failure (911 602 [5.7%]) but varied by age group. Median (interquartile range) length of stay for ECSC ED admissions was longer than non-ECSC ED admissions (3.2 [1.7-5.8] days vs 2.7 [1.4-4.9] days; P < .001). In 2016, median (interquartile range) ED charges per visit for ECSCs were $2736 ($1684-$4605) compared with $2179 ($1118-$4359) per visit for non-ECSC ED visits (P < .001)., Conclusions and Relevance: This comprehensive list of ECSCs can be used to guide indicator development for pre-ED, intra-ED, and post-ED care and overall assessment of the adult, non-mental health, acute care system. Health care utilization and costs among patients with ECSCs are substantial and warrant future study of validation, variations in care, and outcomes associated with ECSCs.

Background: Incarcerated populations worldwide are aging dramatically; in the United States, prisoner mortality rates have reached an all-time high. Little is known about the incarcerated patients who die in community hospitals., Aim: Compare incarcerated and non-incarcerated hospital decedents in California., Design: Cross-sectional study., Setting/participants: All state hospital decedents ( N = 370,831) from 2009 to 2013, decedent age over time examined with additional data (2001-2013)., Results: Overall, 745 incarcerated and 370,086 non-incarcerated individuals died in California hospitals. Incarcerated decedents were more often male (93% vs 51%), Black (19% vs 8%) Latino (27% vs 19%), younger (55 vs 73 years), had shorter hospitalizations (13 vs 16 days), and fewer had an advance care plan (23% vs 36%, p < 0.05). Incarcerated decedents had higher rates of cancer, liver disease, HIV/AIDs, and mental health disorders. Cause of death was disproportionately missing for incarcerated decedents. The average age of incarcerated decedents rose between 2001 and 2013, while it remained stable for others., Conclusion: Palliative care services in correctional facilities should accommodate the needs of relatively young patients and those with mental illness. Given the simultaneous growth in the older prisoner population with the rising age of incarcerated hospital decedents, community hospital clinicians should be prepared to care for seriously ill, incarcerated patients. Significant epidemiologic differences between incarcerated and non-incarcerated decedents in this study suggest the importance of examining the differential palliative care needs of incarcerated patients in all communities.

Background: Timely transport to designated trauma centers impacts mortality following serious injury. We examined whether the distribution of trauma centers in Chicago has created disparities in access to trauma care., Methods: Using the Illinois State Trauma Registry, locations of Chicago-area gunshot wounds (GSWs) from 1999 to 2009 were geocoded and transport times were analyzed for pediatric (age ≤ 15) and adult (age ≥ 16) GSWs., Results: A total of 11,744 included pediatric and adult GSWs were analyzed. Adults experienced longer mean transport times (11.3 vs 10.2 minutes, P < .001). Disproportionate numbers of adult GSW victims experienced over 30-minute transport times on Chicago's south side. Pediatric GSWs demonstrated no such disparity, likely attributable to the presence of a pediatric trauma center on the southeast side., Conclusions: Geographic disparities in access to trauma care exist even within urban trauma systems. The absence of an adult trauma center on Chicago's southeast side has contributed to these disparities., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Timely access to trauma care requires that severely injured patients are ultimately triaged to trauma centers. We sought to determine triage patterns for the injured population within the state of California to determine those factors associated with undertriage., Methods: We conducted a retrospective analysis of all hospital visits in California using the Office of Statewide Health Planning and Development Database from January 1, 2005, and December 31, 2009. All visits associated with injury were linked longitudinally. Sixty-day and one-year mortality was determined using vital statistics data. Primary field triage was defined as field triage to a Level I/II trauma center; retriage was defined as initial triage to a non-Level I/II center followed by transfer to a Level I/II. Regions were organized by local emergency medical services agencies. The primary outcomes were triage patterns and mortality., Results: The undertriage rate was 35% (n = 20,988) but was variable across regions (12-87%). Primary field triage ranged from 7% to 77%. Retriage rates not only were overall low (6% of all severely injured patients) but also varied by region (1-38%). In adjusted analysis, factors associated with a lower odds ratio (OR) of primary field triage included the following: age of 55 years or greater (OR, 0.78; p = 0.001), female sex (OR, 0.88; p = 0.014), greater number of comorbidities (OR, 0.92; p < 0.001), and fall mechanism versus motor vehicle collision (OR, 0.54; p < 0.001). One-year mortality was higher for undertriaged patients (25% vs. 16% and 18% for primary field and retriage, respectively, p < 0.001)., Conclusion: This is the first study to create a longitudinal database of all emergency department visits, hospitalizations, and long-term mortality for every severely injured patient within an entire state during a 5-year period. Undertriage varied substantially by region and was associated with multiple factors including access to care and patient factors., Level of Evidence: Epidemiologic study, level III.

Increasing use of the emergency department (ED) is well documented, but little is known about the type and severity of ED visits or their distribution across safety-net and non-safety-net hospitals. We examined the rates of high-intensity ED visits--characterized by their use of advanced imaging, consultations with specialists, the evaluation of multiple systems, and highly complex medical decision making--by patients with a severe, potentially life-threatening illness in California from 2002 through 2009. Total annual ED visits increased by 25 percent, from 9.0 million to 11.3 million, but high-intensity ED visits nearly doubled, increasing 87 percent from 778,000 to 1.5 million per year. The percentage of ED visits with high-intensity care increased from 9 percent to 13 percent (a relative increase of 44 percent). Annual ED admissions increased by 39 percent overall; most of this increase was attributable to high-intensity ED admissions, which increased by 88 percent. Safety-net EDs experienced an increase in high-intensity visits of 157 percent, compared to an increase of 61 percent at non-safety-net EDs. These findings suggest a trend toward intensification of ED care, particularly at safety-net hospitals, whose patients may have limited access to care outside the ED.

Background: Annual colorectal cancer screening with fecal occult blood test (FOBT) is a noninvasive alternative to screening colonoscopy once every 10 years. If false-positive FOBT results are common, then many patients selecting an FOBT regimen will be exposed to the same invasive testing as those selecting a colonoscopy regimen. The objective of this study was to estimate the probability of experiencing a false-positive after receiving annual FOBT screening for 10 years., Methods: Medical records for patients aged 50 to 79 years receiving FOBT screening with Hemoccult Sensa between 1997 and 2009 at Group Health of Washington State captured the date and results of each FOBT, along with subsequent colorectal cancer diagnoses. We used logistic regression to analyze associations between patient characteristics and odds of a positive FOBT with no invasive cancer diagnosis within 1 year (FOBT+, CRC-). We estimated the probability of receiving at least one FOBT+, CRC- result after 10 years of screening., Results: We observed 181,950 FOBTs from 94,637 individuals. Older patients, males, and non-White patients were significantly more likely to receive FOBT+, CRC- results (P < 0.001 for all risk factors). After 10 years of annual FOBT, 23.0% [95% confidence interval (CI), 18.2-27.0] will receive at least one FOBT+, CRC- result., Conclusions: Most patients participating in annual FOBT screening for 10 years will not have a positive result, reinforcing the potential value of this regimen as a noninvasive alternative to colonoscopy., Impact: Annual stool-based screening is a screening alternative resulting in substantially fewer colonoscopies than once per decade colonoscopy., (©2013 AACR.)

Objectives: We examined whether urban patients who suffered gunshot wounds (GSWs) farther from a trauma center would have longer transport times and higher mortality., Methods: We used the Illinois State Trauma Registry (1999-2009). Scene address data for Chicago-area GSWs was geocoded to calculate distance to the nearest trauma center and compare prehospital transport times. We used multivariate regression to calculate the effect on mortality of being shot more than 5 miles from a trauma center., Results: Of 11,744 GSW patients during the study period, 4782 were shot more than 5 miles from a trauma center. Mean transport time and unadjusted mortality were higher for these patients (P < .001 for both). In a multivariate model, suffering a GSW more than 5 miles from a trauma center was associated with an increased risk of death (odds ratio = 1.23; 95% confidence interval = 1.02, 1.47; P = .03)., Conclusions: Relative "trauma deserts" with decreased access to immediate care were found in certain areas of Chicago and adversely affected mortality from GSWs. These results may inform decisions about trauma systems planning and funding.

Objectives: We examined the charges, their variability, and respective payer group for diagnosis and treatment of the ten most common outpatient conditions presenting to the Emergency department (ED)., Methods: We conducted a cross-sectional study of the 2006-2008 Medical Expenditure Panel Survey. Analysis was limited to outpatient visits with non-elderly, adult (years 18-64) patients with a single discharge diagnosis., Results: We studied 8,303 ED encounters, representing 76.6 million visits. Median charges ranged from $740 (95% CI $651-$817) for an upper respiratory infection to $3437 (95% CI $2917-$3877) for a kidney stone. The median charge for all ten outpatient conditions in the ED was $1233 (95% CI $1199- $1268), with a high degree of charge variability. All diagnoses had an interquartile range (IQR) greater than $800 with 60% of IQRs greater than $1550., Conclusion: Emergency department charges for common conditions are expensive with high charge variability. Greater acute care charge transparency will at least allow patients and providers to be aware of the emergency department charges patients may face in the current health care system.

A combination of analytical and statistical methods is used to improve a tablet coating process guided by quality by design (QbD) principles. A solid dosage form product was found to intermittently exhibit bad taste. A suspected cause was the variability in coating thickness which could lead to the subject tasting the active ingredient in some tablets. A number of samples were analyzed using a laser-induced breakdown spectroscopy (LIBS)-based analytical method, and it was found that the main variability component was the tablet-to-tablet variability within a lot. Hence, it was inferred that the coating process (performed in a perforated rotating pan) required optimization. A set of designed experiments along with response surface modeling and kriging method were used to arrive at an optimal set of operating conditions. Effects of the amount of coating imparted, spray rate, pan rotation speed, and spray temperature were characterized. The results were quantified in terms of the relative standard deviation of tablet-averaged LIBS score and a coating variability index which was the ratio of the standard deviation of the tablet-averaged LIBS score and the weight gain of the tablets. The data-driven models developed based on the designed experiments predicted that the minimum value of this index would be obtained for a 6% weight gain for a pan operating at the highest speed at the maximum fill level while using the lowest spraying rate and temperature from the chosen parametric space. This systematic application of the QbD-based method resulted in an enhanced process understanding and reducing the coating variability by more than half.

Background: Injured patients who are not transported by an ambulance to the hospital are often not included in trauma registries. The outcomes of these patients have until now been unknown. Understanding what happens to nontransports is necessary to better understand triage validity, patient outcomes, and costs associated with injury. We hypothesized that a subset of patients who were not transported from the scene would later present for evaluation and that these patients would have a nonzero mortality rate., Methods: This is a population-based, retrospective cohort study of injured adults and children for three counties in California from 2006 to 2008. Prehospital data for injured patients for whom an ambulance was dispatched were probabilistically linked to trauma registry data from four trauma centers, state-level discharge data, emergency department records, and death files (1-year mortality)., Results: A total of 69,413 injured persons who were evaluated at the scene by emergency medical services were included in the analysis. Of them, 5,865 (8.5%) were not transported. Of those not transported, 1,616 (28%) were later seen in an emergency department and discharged and 92 (2%) were admitted. Seven (0.2%) patients later died., Conclusion: Patients evaluated by emergency medical services, but not initially transported from the field after injury, often present later to the hospital. The mortality rate in this population was not zero, and these patients may represent preventable deaths., Level of Evidence: III, therapeutic study.

Background: Thyroid storm is an often-discussed but rare presentation to emergency departments (EDs). The clinical presentation of a thyroid storm is the result of a hyperthyroid state that may result in significant morbidity or disability, or even death. Typically, patients are aware of their hyperthyroid condition, and may be able to recognize an episode of thyroid storm. However, the first presentation of hyperthyroidism could, in fact, be from thyrotoxic crisis., Objectives: To review the presentation of thyroid storm, including tachycardia, hyperpyrexia, agitation, and altered mental status, which can be easily misdiagnosed as drug intoxication., Case Report: We present the case of an otherwise healthy young adult who was sent to the ED by an outpatient care provider for generalized and vague symptoms of "feeling unwell" that was eventually diagnosed in the ED as thyrotoxic crisis., Conclusion: We use this case to emphasize that thyrotoxic crisis should be at least considered in the differential diagnosis of a patient with this presentation, and to highlight how, even with apparently usual and effective treatments, a patient may still decompensate., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Acyclovir is widely used in the treatment of herpes virus infections, particularly herpes simplex virus and varicella-zoster virus. Acyclovir, when given promptly upon the start of a herpes zoster eruption, speeds healing and diminishes acute pain., Objectives: Because acyclovir is a commonly used medication, it is crucial for health providers to be aware of appropriate dosing as well as possible side effects. We present this case to increase awareness of the potential for inappropriate dosing of acyclovir and the presentations of patients with toxic effects., Case Report: We report the case of a 65-year-old man with a past medical history significant for chronic kidney disease who presented to the Emergency Department with progressive confusion and ataxia over 2 days. Thorough questioning in the patient's native language revealed that he had recently started a medication for a "rash." Neither he nor his family knew the name of the new medication; further investigation revealed it to be acyclovir. Although other diagnoses were considered in the differential diagnosis for this patient with altered mental status, he was treated for presumed acyclovir toxicity and given prompt dialysis, upon which his symptoms resolved., Conclusion: It is important for physicians to remember that even common medications such as acyclovir can have serious side effects and complications. In this case, renal dosing was not used in a patient on hemodialysis. Acyclovir must be renally dosed and carefully monitored through drug level measurement in patients with limited kidney function to prevent serious side effects, such as the neurological sequelae demonstrated in this case report. Emergency physicians should be aware of the potential for inappropriate dosing of this medication and the presentations of patients with toxic effects., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The burden of global injury-related deaths predominantly affects developing countries, which have little infrastructure to evaluate these disparities. We describe injury-related mortality patterns in Kampala, Uganda and compare them with data from the United States and San Francisco (SF), California., Methods: We created a database in Kampala of deaths recorded by the City Mortuary, the Mulago Hospital Mortuary, and the Uganda Ministry of Health from July to December 2007. We analyzed the rate and odds ratios and compared them to data from the U.S. Centers for Disease Control and Prevention and the California Department of Public Health., Results: In Kampala, 25% of all deaths were due to injuries (812/3303) versus 6% in SF and 7% in the United States. The odds of dying of injury in Kampala were 5.0 times higher than in SF and 4.2 times higher than in the United States. Age-standardized death rates indicate a 93% greater risk of dying from injury in Kampala than in SF. The mean age was lower in Kampala than in SF (29 vs. 44 years). The adult injury death rate (rate ratio, or RR) was higher in Kampala than in SF (2.3) or the United States (1.5). Head/neck injury was reported in 65% of injury deaths in Kampala compared to 34% in SF [odds ratio (OR) 3.7] and 28% in the US (OR 4.8)., Conclusions: Urban injury-related mortality is significantly higher in Uganda than in the United States. Injury preferentially affects adults in the prime of their economically productive years. These findings serve as a call for stronger injury prevention and control policies in Uganda.

Objective: To study whether traditionally vulnerable populations have worse geographic access to trauma centers., Design: A cross-sectional analysis using data from the American Hospital Association Annual Survey from 2005 linked with zip code-level data from the US Census. We used a multinomial logit model to examine the odds of having difficult as opposed to easy access to trauma centers for a given subgroup of vulnerable populations., Setting and Participants: Population in rural and urban communities as defined by zip codes in the United States., Main Outcome Measures: Each community's distance to the nearest trauma center (levels I-III)., Results: In urban areas, 67% of the population had easy access to trauma centers and 12% had difficult access compared with 24% and 31% in rural areas, respectively. Areas with higher shares of the following vulnerable population groups had higher risks (odds ratios) of facing difficult access to trauma center services in 2005: foreign born in urban areas (1.65 for a medium share and 2.18 for a high share [both P < .01]); African American in urban and rural areas (1.25 for a medium share and 1.35 for a high share, respectively [both P < .05]); and near-poor in urban and rural areas (1.52 [P < .05] and 1.69 [P < .01] for a high share, respectively)., Conclusions: A significant segment of the US population (representing 38.4 million people) does not have access to trauma care within 1 hour of driving time. Moreover, certain vulnerable groups are at higher risk than others for worse access to trauma centers. Stakeholders and health care planners should consider these factors in the development of trauma systems because a mismatch of potential need and access could signal inefficiencies in the delivery of care.

Emergency care serves a key function within health care systems by providing an entry point to health care and by decreasing morbidity and mortality. Although primarily focused on evaluation and treatment for acute conditions, emergency care also serves as an important locus of provision for preventive care with regard to injuries and disease progression. Despite its important and increasing role, however, emergency care has been frequently overlooked in the discussion of health systems and delivery platforms, particularly in developing countries. Little research has been done in lower- and middle-income countries on the burden of disease reduction attributable to emergency care, whether through injury treatment and prevention, urgent and emergency treatment of acute conditions, or emergency treatment of complications from chronic conditions. There is a critical need for research documenting the role of emergency care services in reducing the global burden of disease. In addition to applying existing methodologies toward this aim, new methodologies should be developed to determine the cost-effectiveness of these interventions and how to effectively cover the costs of and demands for emergency care needs. These analyses could be used to emphasize the public health and clinical importance of emergency care within health systems as policymakers determine health and budgeting priorities in resource-limited settings., (2009 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Objectives: The study objective was to examine the relationship between number of emergency departments (EDs) per capita in California counties and measures of socioeconomic status, to determine whether individuals living in areas with lower socioeconomic levels have decreased access to emergency care., Methods: The authors linked 2005 data from the American Hospital Association (AHA) Annual Survey of Hospitals with the Area Resource Files from the United States Department of Health and Human Services and performed Poisson regression analyses of the association between EDs per capita in individual California counties using the Federal Information Processing Standard (FIPS) county codes and three measures of socioeconomic status: median household income, percentage uninsured, and years of education for individuals over 25 years of age. Multivariate analyses using Poisson regression were also performed to determine if any of these measures of socioeconomic status were independently associated with access to EDs., Results: Median household income is inversely related to the number of EDs per capita (rate ratio = 0.83; 95% confidence interval [CI] = 0.71 to 0.96). Controlling for income in the multivariate analysis demonstrates that there are more EDs per 100,000 population in FIPS codes with more insured residents when compared with areas having less insured residents with the same levels of household income. Similarly, FIPS codes whose residents have more education have more EDs per 100,000 compared with areas with the same income level whose residents have less education., Conclusions: Counties whose residents are poorer have more EDs per 100,000 residents than those with higher median household incomes. However, for the same income level, counties with more insured and more highly educated residents have a greater number of EDs per capita than those with less insured and less educated residents. These findings warrant in-depth studies on disparities in access to care as they relate to socioeconomic status.

Background: Surgical care is emerging as a crucial issue in global public health. Methodology is needed to assess the impact of surgical care from a public health perspective., Methods: A consensus opinion of a group of surgeons, anesthesiologists, and public health experts was established regarding the methodology for estimating the burden of surgical conditions and the unmet need for surgical care., Results: For purposes of analysis, we define surgical conditions as any disease state requiring the expertise of a surgically trained provider. Abnormalities resulting from a surgical condition or its treatment are termed surgical sequelae. Surgical care is defined as any measure that reduces the rates of physical disability or premature death associated with a surgical condition. To measure the burden of surgical conditions and unmet need for surgical care we propose using cumulative disability-adjusted life-year (DALY) curves generated from age-specific population-based data. This conceptual framework is based on the premise that surgically associated disability and death is determined by the incidence of surgical conditions and the quantity and quality of surgical care. The burden of surgical conditions is defined as the total disability and premature deaths that would occur in a population should there be no surgical care; the unmet need for surgical care is defined as the potentially treatable disability and premature deaths due to surgical conditions. Burden of surgical conditions should be expressed as DALYs and unmet need as potential DALYs avertable., Conclusions: Methodology is described for estimating the burden of surgical conditions and unmet need for surgical care. Using this approach it will be feasible to estimate the global burden of surgical conditions and help clarify where surgery fits among other global health priorities. These methods need to be validated using population-based data.

Background: Uganda currently has no organized prehospital emergency system. We sought to measure the current burden of injury seen by lay people in Kampala, Uganda and to determine the feasibility of a lay first-responder training program., Methods: We conducted a cross-sectional survey of current prehospital care providers in Kampala: police officers, minibus taxi drivers, and Local Council officials, and collected data on types and frequencies of emergencies witnessed, barriers to aid provision, history of training, and current availability of first-aid supplies. A context-appropriate course on basic first-aid for trauma was designed and implemented. We measured changes in trainees' fund of knowledge before and after training., Results: A total of 309 lay people participated in the study, and during the previous 6 months saw 18 traumatic emergencies each; 39% saw an injury-related death. The most common injury mechanisms were road crashes, assault, and burns. In these cases, 90% of trainees provided some aid, most commonly lifting (82%) or transport (76%). Fifty-two percent of trainees had previous first-aid training, 44% had some access to equipment, and 32% had ever purchased a first-aid kit. Before training, participants answered 45% of test questions correctly (mean %) and this increased to 86% after training (p < 0.0001)., Conclusions: Lay people witness many emergencies and deaths in Kampala, Uganda and provide much needed care but are ill-prepared to do so. A context-appropriate prehospital trauma care course can be developed and improve lay people's knowledge of basic trauma care. The effectiveness of such a training program needs to be evaluated prospectively.

Background: We previously showed that in the absence of a formal emergency system, lay people face a heavy burden of injuries in Kampala, Uganda, and we demonstrated the feasibility of a basic prehospital trauma course for lay people. This study tests the effectiveness of this course and estimates the costs and cost-effectiveness of scaling up this training., Methods and Findings: For six months, we prospectively followed 307 trainees (police, taxi drivers, and community leaders) who completed a one-day basic prehospital trauma care program in 2008. Cross-sectional surveys and fund of knowledge tests were used to measure their frequency of skill and supply use, reasons for not providing aid, perceived utility of the course and kit, confidence in using skills, and knowledge of first-aid. We then estimated the cost-effectiveness of scaling up the program. At six months, 188 (62%) of the trainees were followed up. Their knowledge retention remained high or increased. The mean correct score on a basic fund of knowledge test was 92%, up from 86% after initial training (n = 146 pairs, p = 0.0016). 97% of participants had used at least one skill from the course: most commonly haemorrhage control, recovery position and lifting/moving and 96% had used at least one first-aid item. Lack of knowledge was less of a barrier and trainees were significantly more confident in providing first-aid. Based on cost estimates from the World Health Organization, local injury data, and modelling from previous studies, the projected cost of scaling up this program was $0.12 per capita or $25-75 per life year saved. Key limitations of the study include small sample size, possible reporter bias, preliminary local validation of study instruments, and an indirect estimate of mortality reduction., Conclusions: Lay first-responders effectively retained knowledge on prehospital trauma care and confidently used their first-aid skills and supplies for at least six months. The costs of scaling up this intervention to cover Kampala are very modest. This may be a cost-effective first step toward developing formal emergency services in Uganda other resource-constrained settings. Further research is needed in this critical area of trauma care in low-income countries.

Background: Access to surgical services is emerging as a crucial issue in global public health. "Effective coverage" is a health metric used to evaluate essential health services in low- and middle-income countries. It measures the fraction of potential health gained that is actually realized for a given intervention by integrating the concepts of need, use, and quality., Methods: This study applies the concept of effective coverage to surgical services by considering injuries and obstetric complications as high-priority surgical conditions in low- and middle-income countries., Results: Effective coverage for both is poor, but it is less well defined for traumatic conditions compared to obstetric conditions owing to a lack of data., Conclusions: More primary and secondary data are critical to measure effective coverage and to estimate the resources required to improve access to surgical services in low- and middle-income countries.

Posttraumatic osteomyelitis may occur as a direct result of bony injury after trauma or arise as a nosocomial infection after the treatment of trauma. Most cases arise after an open fracture, but bony infection can also arise from spread of infection from contiguous soft tissues or by puncture wounds. Motor vehicle accidents, sport injuries, and the use of orthopedic hardware to manage trauma have contributed to the apparent increase in prevalence of posttraumatic osteomyelitis. We report on a case of Pott's Puffy tumor in a previously healthy woman who had an episode of minor forehead trauma 1 month before presentation to the emergency department (ED), complaining of persistent headache and swelling of her forehead. Results of computed tomography (CT) revealed features characteristic of this condition. After postobliteration of the left frontal sinus via a bicoronal approach with an iliac crest bone graft and some dental extractions and 2 weeks of antibiotic therapy, the patient achieved a complete recovery.

Increasing hepatitis B vaccination rates for Asian Americans and Pacific Islanders is a priority. Laws requiring vaccination prior to school enrollment have helped, yet many youths remain unvaccinated. The Hepatitis B Initiative (HBI), launched in 1997 and operated by public health and medical school students, provides free screenings and vaccinations to Boston's Asian American/Pacific Islander community, with a focus on youths. By October 2002, 997 HBI patients from Boston's Chinatown had received free hepatitis B screenings. Of these, 384 patients (39%) were deemed susceptible to the hepatitis B virus and provided with free vaccination.

The genome of Chlamydophila caviae (formerly Chlamydia psittaci, GPIC isolate) (1 173 390 nt with a plasmid of 7966 nt) was determined, representing the fourth species with a complete genome sequence from the Chlamydiaceae family of obligate intracellular bacterial pathogens. Of 1009 annotated genes, 798 were conserved in all three other completed Chlamydiaceae genomes. The C.caviae genome contains 68 genes that lack orthologs in any other completed chlamydial genomes, including tryptophan and thiamine biosynthesis determinants and a ribose-phosphate pyrophosphokinase, the product of the prsA gene. Notable amongst these was a novel member of the virulence-associated invasin/intimin family (IIF) of Gram-negative bacteria. Intriguingly, two authentic frameshift mutations in the ORF indicate that this gene is not functional. Many of the unique genes are found in the replication termination region (RTR or plasticity zone), an area of frequent symmetrical inversion events around the replication terminus shown to be a hotspot for genome variation in previous genome sequencing studies. In C.caviae, the RTR includes several loci of particular interest including a large toxin gene and evidence of ancestral insertion(s) of a bacteriophage. This toxin gene, not present in Chlamydia pneumoniae, is a member of the YopT effector family of type III-secreted cysteine proteases. One gene cluster (guaBA-add) in the RTR is much more similar to orthologs in Chlamydia muridarum than those in the phylogenetically closest species C.pneumoniae, suggesting the possibility of horizontal transfer of genes between the rodent-associated Chlamydiae. With most genes observed in the other chlamydial genomes represented, C.caviae provides a good model for the Chlamydiaceae and a point of comparison against the human atherosclerosis-associated C.pneumoniae. This crucial addition to the set of completed Chlamydiaceae genome sequences is enabling dissection of the roles played by niche-specific genes in these important bacterial pathogens.

The infectious cycle of phiCPG1, a bacteriophage that infects the obligate intracellular pathogen, Chlamydia psittaci strain Guinea Pig Inclusion Conjunctivitis, was observed using transmission electron microscopy of phage-hyperinfected, Chlamydia-infected HeLa cells. Phage attachment to extracellular, metabolically dormant, infectious elementary bodies and cointernalisation are demonstrated. Following entry, phage infection takes place as soon as elementary bodies differentiate into metabolically active reticulate bodies. Phage-infected bacteria follow an altered developmental path whereby cell division is inhibited, producing abnormally large reticulate bodies, termed maxi-reticulate bodies, which do not mature to elementary bodies. These forms eventually lyse late in the chlamydial developmental cycle, releasing abundant phage progeny in the inclusion and, upon lysis of the inclusion membrane, into the cytosol of the host cell. Structural integrity of the hyperinfected HeLa cell is markedly compromised at late stages. Released phage particles attach avidly to the outer leaflet of the outer membranes of lysed and unlysed Chlamydiae at different stages of development, suggesting the presence of specific phage receptors in the outer membrane uniformly during the chlamydial developmental cycle. A mechanism for phage infection is proposed, whereby phage gains access to replicating chlamydiae by attaching to the infectious elementary body, subsequently subverting the chlamydial developmental cycle to its own replicative needs. The implications of phage infection in the context of chlamydial infection and disease are discussed.

Three recently discovered ssDNA Chlamydia-infecting microviruses, phiCPG1, phiAR39, and Chp2, were compared with the previously characterized phage from avian C. psittaci, Chp1. Although the four bacteriophages share an identical arrangement of their five main genes, Chpl has diverged significantly in its nucleotide and protein sequences from the other three, which form a closely related group. The VP1 major viral capsid proteins of phiCPG1 and phiAR39 (from guinea pig-infecting C. psittaci and C. pneumoniae, respectively) are almost identical. However, VP1 of ovine C. psittaci phage Chp2 shows a high rate of nucleotide sequence change localized to a region encoding the "IN5" loop of the protein, thought to be a potential receptor-binding site. Phylogenetic analysis suggests that the ORF4 replication initiation protein is evolving faster than the other phage proteins. phiCPG1, phiAR39, and Chp2 are closely related to an ORF4 homolog inserted in the C. pneumoniae chromosome. This sequence analysis opens the way toward understanding the host-range and evolutionary history of these phages.

Four genes of Chlamydia psittaci strain guinea pig inclusion conjunctivitis (GPIC), whose predicted products are highly homologous to structural and regulatory components of a contact-dependent or type III secretion apparatus, were isolated. Related to genes present in several animal and plant bacterial pathogens, these genes may represent a section of a previously undetected chromosomal virulence locus analogous to several recently described virulence-associated type III secretion loci. The existence of contact-dependent secretion in Chlamydia strongly suggests that these bacteria use pathogenic mechanisms that are similar to those of other intracellular bacterial pathogens. Unlike other intracellular bacteria, however, chlamydiae are metabolically inactive extracellularly and only become capable of global protein synthesis several hours after infection. This implies that chlamydial contact-dependent secretion is only active from within, uniquely after the bacteria have been internalized by eukaryotic cells. The possible role(s) of this pathway in chlamydial pathogenesis are discussed.

The adherence of human strains of Chlamydia trachomatis has been recently shown to be inhibitable by heparin and heparitinase, leading to the proposal that Chlamydia binding to host cells may be mediated by a glycosaminoglycan (GAG)-dependent mechanism. We here describe the adherence of the guinea-pig pathogen, Chlamydia psittaci GPIC, to HeLa cells, which was measured by cytofluorometry with chlamydiae whose DNA was fluorescently labelled. Adherence could be inhibited by heat or trypsin pretreatment of the bacteria, and binding was much faster at 37 degrees C (reaching a plateau within 1 h) than 4 degrees C. Little binding remained when host cells were pre-fixed with paraformaldehyde, suggesting that host cell receptor mobility may be required for effective adherence. Visualization by confocal microscopy confirmed that the bacteria were at or near the host cell surface during the entire time-course of these experiments. Adherence increased as a function of pH between pH 6 and pH 8.0-8.5. Both adherence and infection of HeLa cells could be inhibited with heparin when the adherence step was performed at 4 degrees C, but only infection was inhibited when the adherence step was performed at 37 degrees C, even though heparitinase could block adherence at either 4 degrees C or 37 degrees C. Even at 4 degrees C, heparin-mediated inhibition was significantly lower at pH 8 than pH 7.4, suggesting that GAG-independent mechanisms may play a role in the higher adherence observed at basic pH. These results therefore demonstrate that a GAG-dependent adherence step may be operative in C. psittaci, and raise the possibility that other adherence mechanisms may also contribute to binding by this chlamydial strain. Furthermore, they suggest that there may not be a strict correlation between C. psittaci adherence and the ability to cause productive infections.

The activities of free and liposomal resorcinomycin A against Mycobacterium avium-Mycobacterium intracellulare complex (MAC) grown in broth and in murine peritoneal macrophages were evaluated. Liposomal resorcinomycin A was composed of dimyristoyl phosphatidylcholine and phosphatidylinositol at a molar ratio of 9:1. Both free resorcinomycin A and liposomal resorcinomycin A showed no toxicity to macrophages at concentrations up to 50 micrograms/ml, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Minimal inhibitory concentrations of free resorcinomycin A and liposomal resorcinomycin A in broth were 6 and 12 micrograms/ml, respectively, as determined by the MTT colorimetric microassay. In macrophages, liposomal resorcinomycin A caused significantly higher intramacrophage antimycobacterial activity than the free form of the drug. At doses ranging from 6 to 50 micrograms/ml, liposomal resorcinomycin A caused 50 to 93% MAC growth inhibition, respectively (as determined by CFU), while free resorcinomycin A was associated with 33 to 62% MAC growth inhibition, respectively, 3 days after drug treatment. In addition, antimycobacterial activity of liposomal resorcinomycin A in macrophages was maintained 7 days after treatment, whereas the activity of free resorcinomycin A was reduced to negligible 3 days after treatment. In summary, liposome encapsulation of resorcinomycin A resulted in significant enhancement of antibacterial activity against intramacrophagic MAC infection.

The nucleotide sequence of nearly 6 kb of genomic DNA located immediately upstream of the omp3-omp2 operon of Chlamydia psittaci strain GPIC was obtained, revealing four significant open reading frames (ORFs), named ORF1, ORF2, ORF4 and ORF5. Searches for homologous sequences in the GenBank/EMBL databases have revealed that: (a) the open-ended ORF1 putatively encodes an homolog of RecJ of Escherichia coli, thought to be required for RecBCD-independent and conjugational recombination, and for UV repair; (b) the predicted translation product of ORF4 is highly homologous to the putative product of EUO, a previously described ORF of avian C. psittaci strain 6BC which is preferentially transcribed early during the life cycle; and (c) ORF5 putatively encodes an homolog of bacterial glutamyl-tRNA synthetases. This analysis establishes the genetic linkage of late (omp3-omp2) and of a proposed early (EUO) genes in Chlamydia.

The nucleotide sequence of a 3.1-kb genomic DNA fragment carrying the omp3, omp2 and srp gene homologs from Chlamydia psittaci strain GPIC was determined. A comparative analysis of the GPIC sequence with other chlamydial omp2-linked sequences reveals highly conserved omp3 and omp2 upstream sequences across species, suggesting a unified mechanism of transcription regulation. In contrast, the omp2-srp intergenic segment, which encompasses hypothetical srp transcriptional initiation sites, is relatively less conserved in length and in sequence. Examination of the predicted translation products reveals a high degree of homology within Omp3 and Omp2 across species, with the notable exception of the N-terminal fifth of Omp2. Although the latter segment displays relatively high interspecies sequence variation, it includes a smaller segment, whose high positive charge density is conserved across species, suggesting a conserved structure/function. In contrast to Omp2 and Omp3, a comparative analysis of the predicted amino acid (aa) sequence of the srp product reveals high homology within species, but relatively little across species. A 38-aa segment near the C-terminus of Srp, whose sequence is 64% identical between C. psittaci GPIC and C. trachomatis, is partially truncated in C. psittaci 6BC.

Identification of surface-exposed epitopes on the variant surface glycoproteins (VSGs) of African trypanosomes has been complicated by the observation that most such epitopes are highly conformational. As a result, whenever the molecule is broken down for analysis, the epitope is generally lost. We have exploited the existence of closely related gene families to create chimeric molecules in which particular segments of one VSG are placed in the analogous position of a related but antigenically distinct VSG. The process is used in both a positive and negative manner, so that the epitope can be specifically added or destroyed in a given chimera. As an example, we have used this approach to identify the regions involved in reactivity to a monoclonal antibody specific for VSG117 on the surface of live trypanosomes. We show that while deletion of almost any region of VSG117 results in loss of reactivity to this monoclonal antibody, substituting particular regions with the corresponding segment of the structurally related but antigenically distinct VSG FM8.5 restores reactivity in most but not all cases, thereby delimiting the antigenically key regions. Likewise, substituting key regions from VSG117 into FM8.5 confers reactivity on the resulting chimeras. This approach circumvents some of the problems that result from the highly conformational nature of VSG and should allow further elucidation of the biologically relevant antigenic topology of VSGs.

The chlamydial life cycle involves the intimate interaction of components of the infectious elementary body (EB) surface with receptors on the susceptible eukaryotic cell plasma membrane. We have developed an in vitro ligand binding assay system for the identification and characterization of detergent-extracted EB envelope proteins capable of binding to glutaraldehyde-fixed HeLa cell surfaces. With this assay, the developmentally regulated cysteine-rich envelope protein Omp2 of Chlamydia psittaci strain guinea pig inclusion conjunctivitis was shown to bind specifically to HeLa cells. HeLa cells bound Omp2 selectively over other cell wall-associated proteins, including the major outer membrane protein, and the binding of Omp2 was abolished under conditions which alter its conformation. Furthermore, trypsin treatment, which reduces EB adherence, resulted in the proteolytic removal of a small terminal peptide of Omp2 at the EB surface and inactivated Omp2 in the ligand binding assay, while having a negligible effect on the major outer membrane protein. Collectively, our results suggest that Omp2 possesses the capacity to engage in a specific interaction with the host eukaryotic cell. We speculate that, since Omp2 is present only in the infectious EB form, the observed in vitro interaction may be representative of a determining step of the chlamydial pathogenic process.

The outcome of infection is determined by both the quantity and the quality of an induced immune response. In particular, it has been demonstrated for selected pathogens that induction of TH1 or TH2 type helper T-cell subsets determines whether an immune response gives rise to protective immunity or disease-associated immunopathology. The nature of the antigen and the type of antigen-presenting cells recruited in the induction of a response are critical factors that influence the quality of the immune response. Of particular interest in this respect is the immune response to bacterial particles and the impact of cell wall-associated lipopolysaccharide (LPS) on that response. Nonspecific activation of macrophages and B lymphocytes by LPS could skew the phenotype of activated antigen-presenting cells and selectively alter the immunoglobulin isotypes and helper T-cell subsets that are induced following infection. In an initial attempt to detect immune deviation associated with LPS stimulation, we have compared the immunoglobulin isotypes of antibodies specific for the cysteine-rich outer membrane protein Omp2 induced in normal and LPS-hyporesponsive mice following immunization with Chlamydia psittaci strain guinea pig inclusion conjunctivitis whole elementary bodies. We report that there is a dramatic shift of Omp2-specific antibody from predominantly immunoglobulin G2a (IgG2a) isotype in LPS-hyporesponsive mice to high levels of IgG1 isotype in LPS-responder strains. The dependence of the IgG1 isotype shift on the LPS responder status is linked to the structure of the antigen and its natural processing pathway since LPS-hyporesponsive mice are not, in general, deficient in IgG1 antibody production. In particular, the antibody response to purified recombinant Omp2 is predominantly of the IgG1 isotype even in LPS-hyporesponsive mice.

Chlamydia trachomatis is an important human pathogen. Research to develop a Chlamydia vaccine has focused on the major outer membrane protein (MOMP). Determinants of this protein elicit serovar-specific neutralizing antibodies which are thought to play a critical role in protective immunity. MOMP-specific antibody responses are highly variable in the polymorphic population. Genetic factors which might influence the MOMP-specific immune response are consequently of particular interest. The C. psittaci strain guinea pig inclusion conjunctivitis (GPIC) is a natural pathogen of the guinea pig that causes both ocular and genital tract infections that closely resemble those caused by C. trachomatis in humans. As such, it provides an excellent model for disease. In this report, we explore the influence of major histocompatibility complex-linked genes on the MOMP-specific antibody response in mice immunized with either whole GPIC elementary bodies or recombinant GPIC MOMP. Our results indicate that the MOMP-specific antibody response is major histocompatibility complex linked such that mice of the H-2d haplotype are high responders while mice of the H-2k haplotype are low responders. We demonstrate that MOMP-specific B cells are present in H-2k strains which are, however, deficient in MOMP-specific helper T cells. Although immunization of low-MOMP-responder strains with whole chlamydial elementary bodies induces high levels of immunoglobulin G antibody specific for Omp2, the cysteine-rich outer membrane protein, MOMP-specific B cells are unable to receive help from Omp2-specific T cells. The failure of intermolecular help from Omp2-specific T cells and related observations raise important issues regarding the processing and presentation of chlamydial antigens and the design of optimal subunit vaccines.

While enteroinvasive Escherichia coli (EIEC) and shigellae are genotypically nearly identical, a difference has been reported in the infective dose to humans: EIEC is 10,000-fold less infectious than shigellae. A possible basis for this difference lies in the inherent invasiveness of these bacteria toward epithelial cells. Thus, despite the high degree of homology between the invasion plasmids of EIEC and shigellae, substantial differences in genetic organization and/or sequence may exist. We have undertaken a systematic genetic analysis of the EIEC plasmid pSF204, using transposon mutagenesis. Congo red-negative TnphoA insertion mutants (Pcr- PhoA-) and TnphoA fusion mutants (PhoA+) were isolated and screened for the ability to invade cultured HEp-2 cells. Most invasion-negative (Inv-) mutations mapped to a 30-kb segment of the invasion plasmid, including homologs of the Shigella flexneri ipa, mxi, and spa genes. Inv- PhoA+ fusions in the EIEC ipaC, mxiG, mxiJ, mxiM, and mxiD homologs and in a proposed new gene, named invX, located downstream of the spa region were identified and characterized. This analysis indicates the presence of the ipaC, mxiG, mxiJ, mxiM, mxiD, and invX gene products in the EIEC cell envelope and demonstrates a strict requirement for these genetic loci in invasion. Overall, our results suggest a high degree of genetic, structural, and functional homology between the EIEC and S. flexneri large invasion plasmids.

The immunological and cellular properties of cultured normal and fetal brain cells as well as glioma cells were compared. They were grown successfully in tissue culture media. Results from the growth properties and karyotype analysis indicated that cultured cells from normal and fetal brain tissues were normal and could be passaged limited times. The fetal brain cells had a longer life span than normal brain cells in the culture and their morphology exhibited variations according to cell passages. Two glioma cell lines, designated as G-5-T and G-9-T were established. The G-5-T and G-9-T had different morphology. Both G-5-T and G-9-T formed colonies in the soft agar. However, only G-9-T cells grew as large tumors in nude mice. Neither cell line secreted CEA, AFP and did not contain GFAP and S-100 protein. As measured by the 51Cr cytotoxicity assay, G-9-T but not G-5-T cells possessed D/DR antigens.