bluuebunny/crossref_metadata_2025 huggingface dataset:
The S‐transform with windows of arbitrary and varying shape
Authors: Pinnegar C. Robert , Mansinha Lalu
Published: March 2003

The S‐transform is an invertible time‐frequency spectral localization technique which combines elements of wavelet transforms and short‐time Fourier transforms. In previous usage, the frequency dependence of the analyzing window of the S‐transform has been through horizontal and vertical dilations of a basic functional form, usually a Gaussian. In this paper, we present a generalized S‐transform in which two prescribed functions of frequency control the scale and the shape of the analyzing window, and apply it to determining P‐wave arrival time in a noisy seismogram. The S‐transform is also used as a time‐frequency filter; this helps in determining the sign of the P arrival.
Latest views of the sparse Radon transform
Authors: Trad Daniel , Ulrych Tadeusz , Sacchi Mauricio
Published: March 2003

The Radon transform (RT) suffers from the typical problems of loss of resolution and aliasing that arise as a consequence of incomplete information, including limited aperture and discretization. Sparseness in the Radon domain is a valid and useful criterion for supplying this missing information, equivalent somehow to assuming smooth amplitude variation in the transition between known and unknown (missing) data. Applying this constraint while honoring the data can become a serious challenge for routine seismic processing because of the very limited processing time available, in general, per common midpoint. To develop methods that are robust, easy to use and flexible to adapt to different problems we have to pay attention to a variety of algorithms, operator design, and estimation of the hyperparameters that are responsible for the regularization of the solution.

In this paper, we discuss fast implementations for several varieties of RT in the time and frequency domains. An iterative conjugate gradient algorithm with fast Fourier transform multiplication is used in all cases. To preserve the important property of iterative subspace methods of regularizing the solution by the number of iterations, the model weights are incorporated into the operators. This turns out to be of particular importance, and it can be understood in terms of the singular vectors of the weighted transform. The iterative algorithm is stopped according to a general cross validation criterion for subspaces. We apply this idea to several known implementations and compare results in order to better understand differences between, and merits of, these algorithms.
Amiodarone and Bretylium in the Treatment of Hypothermic Ventricular Fibrillation in a Canine Model
Authors: Stoner Jason , Martin Gerard , O'Mara Kevin , Ehlers Joseph , Tomlanovich Michael
Published: March 2003

Refractory ventricular fibrillation (VF) is a complication of severe hypothermia. Despite mixed experimental data, some authors view bretylium as the drug of choice in hypothermic VF. Bretylium was removed from Advanced Cardiac Life Support guidelines, and, to date, efficacy of amiodarone in hypothermia is unknown. Objectives: To compare defibrillation rates from hypothermic VF after drug therapy with amiodarone, bretylium, and placebo. Methods: This was a randomized, blinded, and placebo‐controlled laboratory experiment. Thirty anesthetized dogs were mechanically ventilated and instrumented to monitor coronary perfusion pressure (CPP), rectal core temperature, and electrocardiogram (ECG). Animals were cooled to 22°C or the onset of spontaneous VF. Ventricular fibrillation was induced as needed with a transthoracic AC current. Cardiopulmonary resuscitation (CPR) was initiated and animals were randomized (n= 10 each group) to receive amiodarone 10 mg/kg (A), bretylium 5 mg/kg (B), or placebo (P) intravenously. CPR was continued while monitoring for chemical defibrillation. Rewarming was limited to removal from the cold environment. After 10 minutes, up to three escalating defibrillatory shocks were administered. Hemodynamic monitoring continued after resuscitation. Return of spontaneous circulation (ROSC) was defined as a sustainable ECG rhythm generating a corresponding arterial pressure tracing lasting a minimum of 15 minutes. Sample size permitted 80% power to detect a 60% difference in conversion rate between groups. Results: CPR was adequate based on CPP > 15 mm Hg in all animals. Mean (±SD) CPP was 35.3 ± 18.8 mm Hg with an overall lower trend in the amiodarone group (p = 0.06). Baseline variables were similar between groups. No instance of chemical defibrillation was noted. There was no significant difference in ROSC rates between groups. Resuscitation rates were: amiodarone = 1/10, bretylium = 4/10, and placebo = 3/10 (p = 0.45). Conclusions: In this model of severe hypothermic VF, neither amiodarone nor bretylium was significantly better than placebo in improving the resuscitation rate.
A Randomized Controlled Trial of Intravenous Aminophylline for Atropine‐resistant Out‐of‐hospital Asystolic Cardiac Arrest
Authors: Mader Timothy J. , Smithline Howard A. , Durkin Lou , Scriver Geoffrey
Published: March 2003

Objectives: Myocardial ischemia, during cardiopulmonary arrest, can lead to atropine‐resistant bradyasystole from interstitial accumulation of endogenous adenosine. Aminophylline is a nonspecific adenosine receptor antagonist capable of reversing ischemia‐induced bradyasystole in a variety of settings. The hypothesis of this study was that aminophylline improves the rate of return of spontaneous circulation (ROSC) in atropine‐resistant asystolic out‐of‐hospital cardiac arrest when used early in the resuscitation effort. Methods: This was a prospective, randomized, double‐blinded, placebo‐controlled trial set in an urban emergency medical services system serving a population of 250,000. All non‐pregnant, normothermic adults suffering nontraumatic out‐of‐hospital cardiac arrest (February 1999 to August 2000) with asystole were eligible. Patients remaining in asystole after initial doses of epinephrine and atropine received either aminophylline 250 mg or matching placebo as a bolus injection through a peripheral intravenous line. All other aspects of the attempted resuscitation proceeded in accordance with standard Advanced Cardiac Life Support (ACLS) guidelines. A sample size of 102 patients was calculated to yield a power of 80% to show an absolute improvement of 25% in ROSC. The aminophylline and control groups were compared by calculating 95% confidence intervals (95% CIs) and the data were modeled using logistic regression. Results: The investigators enrolled 112 consecutive patients. One subject was dropped prior to analysis because of missing data. Data for 111 patients were analyzed on an intention‐to‐treat basis. Baseline characteristics were similar for the two groups. Comparing the control and aminophylline groups, ROSC was achieved in 15.6% (95% CI = 6% to 29%) and 22.7% (95% CI = 13% to 35%), while reversal of asystole occurred in 26.7% (95% CI = 15% to 42%) and 40.9% (95% CI = 29% to 54%), respectively. Group allocation had an odds ratio of 1.8 (95% CI = 0.6 to 5.3) for ROSC. Witnessed arrest was an independent predictor of outcome with an odds ratio of 3.8 (95% CI = 1.3 to 11.2). Conclusions: Addition of aminophylline appears to be a promising new intervention in the ACLS treatment of atropine‐resistant asystolic out‐of‐hospital cardiac arrest.
Uncovering Heart Failure in Patients with a History of Pulmonary Disease: Rationale for the Early Use of B‐type Natriuretic Peptide in the Emergency Department
Authors: McCullough Peter A. , Hollander Judd E. , Nowak Richard M. , Storrow Alan B. , Duc Philippe , Omland Torbjørn , McCord James , Herrmann Howard C. , Steg Philippe G. , Westheim Arne , Knudsen Cathrine Wold , Abraham William T. , Lamba Sumant , Wu Alan H.B. , Perez Alberto , Clopton Paul , Krishnaswamy Padma , Kazanegra Radmila , Maisel Alan S.
Published: March 2003

Plasma B‐type natriuretic peptide (BNP) can reliably identify acute congestive heart failure (CHF) in patients presenting to the emergency department (ED) with acute dyspnea. Heart failure, asthma, and chronic obstructive pulmonary disease (COPD) are syndromes where dyspnea and wheezing are overlapping signs, and hence, these syndromes are often difficult to differentiate. Objective: To determine whether BNP can distinguish new‐onset heart failure in patients with COPD or asthma presenting with dyspnea to the ED. Methods: The BNP Multinational Study was a seven‐center prospective study of 1,586 adult patients presenting to the ED with acute dyspnea who had blinded BNP levels measured on arrival with a rapid, point‐of‐care device. This study evaluated the 417 patients with no previous history of heart failure and a history of asthma or COPD as a subgroup from the 1,586 adult patients in the BNP Multinational Study. The reference standard for CHF was adjudicated by two independent cardiologists, also blinded to BNP results, who reviewed all clinical data and standardized CHF scores. Results: A total of 417 subjects (mean age 62.2 years, 64.4% male) had a history of asthma or COPD without a history of CHF. Of these, 87/417 (20.9%, 95% CI = 17.1% to 25.1%) were found to have CHF as the final adjudicated diagnosis. The emergency physicians identified a minority, 32/87 (36.8%), of these patients with CHF. The mean BNP values (± SD) were 587.0 ± 426.4 and 108.8 ± 221.3 pg/mL for those with and without CHF (p < 0.0001). At a cutpoint of 100 pg/mL, BNP had the following decision statistics: sensitivity 93.1%, specificity 77.3%, positive predictive value 51.9%, negative predictive value 97.7%, accuracy 80.6%, positive likelihood ratio 4.10, and negative likelihood ratio 0.09. If BNP would have been added to clinical judgment (high ≥ 80% probability of CHF), at a cutpoint of 100 pg/mL, 83/87 (95.4%) of the CHF subjects would have been correctly diagnosed. Multivariate analysis found BNP to be the most important predictor of CHF (OR = 12.1, 95% CI = 5.4 to 27.0, p < 0.0001). In the 87 subjects found to have CHF, 39.0%, 22.2%, and 54.8% were taking angiotensin‐converting enzyme inhibitors (ACEIs), beta‐blockers (BBs), and diuretics on a chronic basis, respectively. Conclusions: The yield of adding routine BNP testing in patients with a history of asthma or COPD in picking up newly diagnosed CHF is approximately 20%. This group of patients presents a substantial therapeutic opportunity for the initiation and chronic administration of ACEI and BB therapy, as well as other CHF management strategies.
Can Electrocardiographic Criteria Predict Adverse Cardiac Events and Positive Cardiac Markers?
Authors: Blomkalns Andra L. , Lindsell Christopher J. , Chandra Abhinav , Osterlund Mary E. , Gibler W. Brian , Pollack Charles V. , Tiffany Brian R. , Hollander Judd E. , Hoekstra James W.
Published: March 2003

Objectives: To determine electrocardiogram (ECG) predictors of positive cardiac markers and short‐term adverse cardiac events in an undifferentiated chest pain population presenting to emergency departments (EDs). The authors hypothesized that specific ECG findings, other than those previously identified in higher‐risk populations, would be predictive of cardiac outcomes and positive cardiac markers. Methods: This study used data from a prospectively collected, retrospectively analyzed Internet‐based data registry of undifferentiated chest pain patients (i*trACS). Logistic regression modeling was performed to determine the ECG findings that were predictive of 1) positive cardiac markers and 2) short‐term adverse cardiac events. Results: ST‐segment elevation (STE), ST‐segment depression (STD), pathological Q‐waves (PQW), and T‐wave inversion were associated with increased odds of percutaneous coronary intervention or catheterization, myocardial infarction, or coronary artery bypass grafting. The odds of creatine kinase–MB (CK‐MB) measuring positive were increased if STE, STD, or PQW were present [odds ratio (OR) 2.495, 2.582, and 1.295, respectively]. A right bundle branch block tended to decrease the odds of CK‐MB measuring positive (OR 0.658). A similar pattern of results was observed for troponin I (OR 3.608 for STE, 3.72 for STD, 1.538 for PQW). Troponin T showed an increased odds of measuring positive if any of STE, STD, left bundle branch block, or T‐wave inversion were evident (OR 2.313, 2.816, 1.80, and 1.449, respectively). Conclusions: Initial ECG criteria can be used to predict short‐term cardiac outcomes and positive cardiac markers. These findings can be important aids in the risk‐stratification and aggressive treatment regimens of chest pain patients presenting to EDs.
Visual Analog Pain Scores Do Not Define Desire for Analgesia in Patients with Acute Pain
Authors: Blumstein Howard A. , Moore Dave
Published: March 2003

Increased attention to improving the provision of analgesia has led to calls for increased use of pain measurement systems, including visual analog scales, which have not been validated for use in clinical care. Objective: To evaluate the ability of the visual analog scale to differentiate between patients with acute, painful conditions requiring pain medication, and those not requiring analgesia. Methods: This was a prospective, observational study of a convenience sample of patients with acute pain. Subjects were asked about their desire for medication. Visual analog scale pain scores were determined. Results: One hundred four patients participated. Patients requesting pain medication had a mean visual analog scale score of 66. The mean score for those not requesting medication was 45. The difference between the means was 21 [95% confidence interval (95% CI) for difference between the means was 10.7]. The area under the receiver operating characteristic curve for the visual analog scale was 0.72 (95% CI = 0.61 to 0.82). Conclusions: The visual analog scale cannot adequately discriminate between those patients who do and do not desire analgesia.
Nebulized Fentanyl for Relief of Abdominal Pain
Authors: Bartfield Joel M. , Flint Robert D. , McErlean Mara , Broderick John
Published: March 2003

Objective: To compare the efficacies of nebulized vs. intravenous fentanyl for the relief of abdominal pain.Methods: This randomized, double‐blind, double‐placebo‐controlled study compared nebulized and intravenous fentanyl (1.5 μg/kg). Group I received intravenous fentanyl and nebulized saline. Group II received nebulized fentanyl and intravenous saline. Pain scores were measured at baseline and at 15 and 30 minutes after the study drug, using a 100‐mm visual analog scale. Thirty minutes after the study drug, the subjects were offered rescue medication. The groups were compared for changes in pain scores at 30 minutes (primary outcome, t‐test), changes in pain scores at 15 minutes (t‐test), and need for rescue medication (Fisher's exact test). Significance was defined as p < 0.05. Results: Fifty subjects (24 group I, 26 group II) were enrolled. The groups were similar with respect to mean baseline pain (72 mm group I, 74 mm group II) and demographics. A statistically significant difference in changes in pain scores at 15 minutes favoring group I (25 mm vs. 10 mm, p = 0.005) was not evident by 30 minutes (25 mm vs. 16 mm, p = 0.24). The groups were not different with respect to need for rescue medication (50% in group I compared with 69% in group II, p = 0.25). Conclusions: Nebulized fentanyl provides comparable analgesia to that of intravenous fentanyl.
Evaluation of Emergency Medicine Resident Death Notification Skills by Direct Observation
Authors: Benenson Ronald S. , Pollack Marc L.
Published: March 2003

Emergency physicians commonly perform death notifications. Physician training in death notification has been limited. Resident physicians are rarely evaluated in their performance of death notifications. Objective: To evaluate death notification skills by direct observation of actual notifications performed by trained emergency medicine (EM) residents. Methods: This was a prospective, observational study of EM resident death notification performance. EM residents received training and then were directly observed and evaluated by trained evaluators during actual death notifications in a 64,000‐visit community teaching hospital emergency department. Results: There were 327 evaluations of 70 different EM residents. Overall performance evaluations were 55% excellent, 40% satisfactory, and 5% unsatisfactory. Third‐year EM residents and female EM residents were more likely to be rated excellent. Conclusions: Death notification is a skill that can be evaluated like other EM skills. Trained EM residents performed well in actual death notifications when directly observed and evaluated. Senior residents and female residents were more likely to be rated excellent.
A Brief Risk‐stratification Tool to Predict Repeat Emergency Department Visits and Hospitalizationsin Older Patients Discharged from the Emergency Department
Authors: Meldon Stephen W. , Mion Lorraine C. , Palmer Robert M. , Drew Barbara L. , Connor Jason T. , Lewicki Linda J. , Bass David M. , Emerman Charles L.
Published: March 2003

Objectives: To evaluate the predictive ability of a simple six‐item triage risk screening tool (TRST) to identify elder emergency department (ED) patients at risk for ED revisits, hospitalization, or nursing home (NH) placement within 30 and 120 days following ED discharge. Methods: Prospective cohort study of 650 community‐dwelling elders (age 65 years or older) presenting to two urban academic EDs. Subjects were prospectively evaluated with a simple six‐item ED nursing TRST. Participants were interviewed 30 and 120 days post‐ED index visit and the utilization of EDs, hospitals, or NHs was recorded. Main outcome measurement was the ability of the TRST to predict the composite endpoint of subsequent ED use, hospital admission, or NH admission at 30 and 120 days. Individual outcomes of ED use, hospitalization, and NH admissions were also examined. Results: Increasing cumulative TRST scores were associated with significant trends for ED use, hospital admission, and composite outcome at both 30 and 120 days (p < 0.0001 for all, except 30‐day ED use, p = 0.002). A simple, unweighted five‐item TRST (“lives alone” item removed after logistic regression modeling) with a cut‐off score of 2 was the most parsimonious model for predicting composite outcome (AUC = 0.64) and hospitalization at 30 days (AUC = 0.72). Patients defined as high‐risk by the TRST (score ≥ 2) were significantly more likely to require subsequent ED use (RR = 1.7; 95% CI = 1.2 to 2.3), hospital admission (RR = 3.3; 95% CI = 2.2 to 5.1), or the composite outcome (RR = 1.9; 95% CI 1.7 to 2.9) at both 30 days and 120 days than the low‐risk cohort. Conclusions: Older ED patients with two or more risk factors on a simple triage screening tool were found to be at significantly increased risk for subsequent ED use, hospitalization, and nursing home admission.
Rapid Two‐stage Emergency Department Intervention for Seniors: Impact on Continuity of Care
Authors: McCusker Jane , Dendukuri Nandini , Tousignant Pierre , Verdon Josée , Poulin de Courval Louise , Belzile Eric
Published: March 2003

Objectives: A two‐stage intervention comprising screening and a brief standardized nursing assessment and referral, for emergency department (ED) patients aged 65 years and over, reduced the rate of functional decline four months after the visit, without increasing societal costs. In this study, the authors investigated the effects of the intervention on the process of care at, and during the month after, the ED visit. Methods: Patients at four Montreal hospital EDs were randomized by day of visit to the intervention or to usual care. Patients admitted to the hospital were excluded. Measures of process of care included: referrals and visits to the primary physician and to the local community health center, for home care or other services, and return ED visits. Data sources included hospital charts, patient questionnaires, and provincial administrative databases. Results: The study sample included 166 intervention and 179 control group patients ready for discharge from the ED. Intervention group patients were more likely to have a chart‐documented referral to their local community health center [adjusted odds ratio (OR) 4.0, 95% confidence interval (95% CI) = 1.7 to 9.5] and their primary physician [adjusted OR 1.9, 95% CI = 1.0 to 3.4], and to have received home care services one month after the ED visit [adjusted OR 2.3, 95% CI = 1.1 to 5.1]. Unexpectedly, they were also more likely to make a return visit to the ED [adjusted OR 1.6, 95% CI = 1.0 to 2.6]. Conclusions: The beneficial outcomes of the intervention appear to result primarily from the early provision of home care rather than early contact with the primary physician.
Geriatric Trauma Patients—Are They Receiving Trauma Center Care?
Authors: Lane Peter , Sorondo Barbara , Kelly John J.
Published: March 2003

Objectives: The primary purpose of this study was to evaluate whether severely injured geriatric patients were as likely to be treated at designated trauma centers (TCs) within the statewide trauma system. The secondary objective was to compare the demographic and injury characteristics of severely injured older and young patients who received care in TCs with the characteristics of those patients cared for in non‐TCs. Methods: The authors reviewed files for all acute injury discharges in Pennsylvania for 1997. Injury diagnoses were mapped to Abbreviated Injury Scale (AIS) scores using ICDMAP software; the Injury Severity Score (ISS) was computed. The frequency of hospital discharges for injury from TC and non‐TC hospitals in both the older (E) (≥65 years) and younger (Y) (<65 years) groups were computed, and compared using chi‐square testing for significance. Logistic regression was performed to assess the influence of various factors. Severity of injury was controlled for with both ISS and Maximum AIS (MAIS). Results: 107,358 patients were admitted to hospitals in the state because of injury; 8,980 had an ISS > 15; 5,855 were Y and 3,125 were E. Forty‐seven percent of the Y patients received TC care compared with only 36.6% of the E patients (p < 0.001). Logistic regression analysis showed that age was a strongly negative predictor for TC care when injury severity was controlled. Conclusions: Seriously injured older patients were less likely to receive care in a trauma center than younger patients.
A Research Agenda for Geriatric Emergency Medicine
Authors: Wilber Scott T. , Gerson Lowell W.
Published: March 2003

Objectives: The Research Agenda Setting Process (RASP), part of the American Geriatric Society's (AGS's) project “Increasing Geriatric Expertise in Surgical and Related Medical Specialties,” was designed to define a research agenda for the geriatrics aspects of participating specialties. This paper presents a summary of the research agenda for emergency medicine. Methods: The RASP was developed by the AGS in conjunction with experts from the participating specialty organizations. A “content expert” (CE) for each specialty developed a Medline search strategy in conjunction with RAND Health librarians. The CE reviewed the search to identify papers that were germane to research in the emergency care of older patients. The CE and a senior writing group member drafted a paper that synthesized the current literature and suggested areas for further research. A panel consisting of AGS members and emergency physicians with geriatrics expertise reviewed this paper. The research agenda was further refined at a two‐day retreat. Two senior geriatricians reviewed the resulting paper. Results: The Medline search for emergency medicine resulted in a list of 3,348 articles; 299 articles were pertinent and reviewed. The search for trauma resulted in a list of 1,838 articles; 133 were reviewed. Research agenda items were defined for multiple topics within geriatric emergency medicine and trauma. Conclusion: A research agenda for geriatric emergency medicine has been developed, using a combination of review of current literature and expert opinion.
Patient Satisfaction Data as a Quality Indicator: A Tale of Two Emergency Departments
Authors: Boudreaux Edwin D. , Mandry Cris V. , Wood Karen
Published: March 2003

Objective: Patient satisfaction is a commonly measured indicator of quality emergency care. However, the existing empirical literature on emergency department (ED) patient satisfaction provides little guidance on how to analyze, interpret, and use data obtained in the clinical setting. Using two EDs as examples, the authors describe practical strategies designed to identify priority areas for potential improvement. Methods: The authors used a cross‐sectional, observational design. All patients who presented for emergency care during the designated time periods were eligible. Patients were randomly selected, contacted by telephone, and surveyed using three measures of global satisfaction, 23 perceived quality‐of‐care indicators, and six perceived wait times. Descriptive statistics were calculated. Comparisons were made of each of the perceived care and wait time indicators against explicitly defined acceptability criteria to determine satisfiers/dissatisfiers. Each indicator was correlated with the three global satisfaction indices. The authors integrated results obtained from applying the acceptability criteria with those obtained from the correlations to yield priority indicators for remediation and maintenance strategies. Results: For hospitals A and B, respectively, 15 (52%) and 16 (55%) of perceived care and wait time indicators failed to meet acceptability criteria. Using the correlations with overall satisfaction, the authors further narrowed the priority areas for remediation to six indicators for hospital A and three indicators for hospital B. One maintenance indicator was revealed for hospital A and four for hospital B. Conclusions: A combination of applying explicit acceptability criteria to descriptive statistics and using correlation coefficients with overall satisfaction can help to maximize the usefulness of patient satisfaction data by uncovering priority areas. These priority areas were broken down into maintenance and remediation indicators and were found to vary considerably depending on the hospital in question. Such strategies can help to refine performance improvement efforts by targeting those domains with the greatest impact on overall satisfaction.
Preventive Care in the Emergency Department: Should Emergency Departments Conduct Routine HIV Screening? A Systematic Review
Authors: Rothman Richard E. , Ketlogetswe Kerunne S. , Dolan Teresa , Wyer Peter C. , Kelen Gabor D.
Published: March 2003

Objective: To perform a systematic review of the emergency medicine literature to assess the appropriateness of offering routine HIV screening to patients in the emergency department (ED). Methods: The systematic review was conducted with the aid of a structured template, a companion explanatory guide, and a grading and methodological scoring system based on published criteria for critical appraisal. Two reviewers conducted independent searches using OvidR, PubMed, MD Consult, and Grateful Med. Relevant abstracts were reviewed; those most pertinent to the stated objective were selected for complete evaluation using the structured template. Results: Fifty‐two relevant abstracts were reviewed; of these, nine were selected for detailed evaluation. Seven ED‐based prospective cross‐sectional seroprevalence studies found HIV rates of 2–17%. Highest rates of infection were seen among patients with behavioral risks such as male homosexual activity and intravenous drug use. Two studies demonstrated feasibility of both standard and rapid HIV testing in the ED, with more than half of the patients approached consenting to testing by either method, consistent with voluntary testing acceptance rates described in other settings. Several cost–benefit analyses lend indirect support for HIV screening in the ED. Conclusions: Multiple ED‐based studies meeting the Centers for Disease Control and Prevention Guideline threshold to recommend routine screening, in conjunction with limited feasibility trials and extrapolation from cost–benefit studies, provide evidence to recommend that EDs offer HIV screening to high‐risk patients (i.e., those with identifiable risk factors) or high‐risk populations (i.e., those where HIV seroprevelance is at least 1%).
Oral Treatment of Organophosphate Poisoning in Mice
Authors: Bowls Bradford J. , Freeman Jack M. , Luna James A. , Meggs William J.
Published: March 2003

Objective: Organophosphates are used as pesticides, herbicides, and chemical warfare agents. Treatment of organophosphate poisoning is with intravenous atropine and pralidoxime in addition to supportive care. This study determined the efficacy of oral agents in preventing death from organophosphate poisoning. Methods: The organophosphate paraoxon (8 mg/kg) was used in a murine model with lethality at four and 24 hours as an end point. For oral treatment, 15 male Balbc mice were given either atropine sulfate (4 mg/kg), or a combination of atropine sulfate (4 mg/kg) with pralidoxime (100 mg/kg), by oral gavage. A control group of 22 mice received water by oral gavage. Chi‐square analysis was used to compare results in the different groups. Results: Of the control group, six of 22 survived to four hours after paraoxon exposure. Of the exposed animals treated with oral atropine, eight of 15 survived to four hours. Of the exposed animals treated with a combination of atropine and pralidoxime, 13 of 15 survived to four hours. All animals surviving to four hours survived to 24 hours. The increased survival of animals in the atropine group relative to the control group was not significant (p = 0.09). Survival was significant in the group treated with atropine and pralidoxime relative to atropine alone (p = 0.02) and to the control group (p = 0.0002). All treated mice surviving at four hours were alive at 24 hours. Conclusions: Both oral atropine and a combination of oral atropine and pralidoxime improved survival, and combination therapy achieved statistical significance. Generalization of this result to other organophosphate pesticides, other doses of paraoxon, and other species cannot be made without further investigations.
Can Some Growth Hormone (GH)-Deficient Children Benefit from Combined Therapy with Gonadotropin-Releasing Hormone Analogs and GH? Results of a Retrospective Study
Authors: Tauber M. , Berro B. , Delagnes V. , Lounis N. , Jouret B. , Pienkowski C. , Oliver I. , Rochiccioli P.
Published: March 2003

Recombinant GH (rGH) treatment does not invariably correct height deficits in GH-deficient children once puberty has begun. The addition of GnRH analogs (GnRHa) to delay puberty has been advocated, but published results are few and sometimes conflicting.

We retrospectively compared GH-deficient children treated with rGH and GnRHa for at least 1 yr after entering puberty and having attained their final height (n = 23) with a matched control group treated only with rGH. Overall, combined therapy did not significantly increase final height relative to rGH alone. However, the shortest girls at the onset of puberty (<25th percentile) benefited more than the tallest (>75th percentile) in both final height relative to predicted height and pubertal catch-up growth.

In the control group, patients having experienced intrauterine growth retardation (IUGR) attained a lower mean final height than patients without IUGR (difference significant in boys, but not in girls). In the combined therapy group, IUGR did not affect the final height of either sex.

Our results suggest that two populations might benefit most from combined GnRHa and rGH therapy: girls particularly short at the onset of puberty and patients who had experienced IUGR. Further prospective studies are required to confirm these preliminary hypothesis.
Zone-Dependent Expression of Estrogen Receptors α and β in Human Benign Prostatic Hyperplasia
Authors: Tsurusaki Toshifumi , Aoki Daiyu , Kanetake Hiroshi , Inoue Satoshi , Muramatsu Masami , Hishikawa Yoshitaka , Koji Takehiko
Published: March 2003

Estrogen, which acts through estrogen receptors (ERs) α and β, has been implicated in the pathogenesis of benign and malignant human prostatic tumors, i.e. benign prostatic hyperplasia and prostate cancer, thought to originate from different zones of the prostate [the transition zone (TZ) and peripheral zone (PZ), respectively]. Here, we examined the cellular distribution of ERα and ERβ in human normal and hyperplastic prostate tissues, using in situ hybridization and immunohistochemistry. ERα expression was restricted to stromal cells of PZ. In contrast, ERβ was expressed in the stromal cells of PZ as well as TZ. ERβ-positive epithelial cells were evenly distributed in PZ and TZ of the prostate. Our results suggest that estrogen may play a crucial role in the pathogenesis of benign prostatic hyperplasia through ERβ.
Regulation of motor neuron subtype identity by repressor activity of Mnx class homeodomain proteins
Authors: William Christopher M. , Tanabe Yasuto , Jessell Thomas M.
Published: March 2003

In the developing spinal cord, motor neurons acquire columnar subtype identities that can be recognized by distinct profiles of homeodomain transcription factor expression. The mechanisms that direct the differentiation of motor neuron columnar subtype from an apparently uniform group of motor neuron progenitors remain poorly defined. In the chick embryo,the Mnx class homeodomain protein MNR2 is expressed selectively by motor neuron progenitors, and has been implicated in the specification of motor neuron fate. We show here that MNR2 expression persists in postmitotic motor neurons that populate the median motor column (MMC), whereas its expression is rapidly extinguished from lateral motor column (LMC) neurons and from preganglionic autonomic neurons of the Column of Terni (CT). The extinction of expression of MNR2, and the related Mnx protein HB9, from postmitotic motor neurons appears to be required for the generation of CT neurons but not for LMC generation. In addition, MNR2 and HB9 are likely to mediate the suppression of CT neuron generation that is induced by the LIM HD protein Lim3. Finally, MNR2 appears to regulate motor neuron identity by acting as a transcriptional repressor, providing further evidence for the key role of transcriptional repression in motor neuron specification.
Defective somite patterning in mouse embryos with reduced levels ofTbx6
Authors: White Phillip H. , Farkas Deborah R. , McFadden Erin E. , Chapman Deborah L.
Published: March 2003

During vertebrate embryogenesis, paraxial mesoderm gives rise to somites,which subsequently develop into the dermis, skeletal muscle, ribs and vertebrae of the adult. Mutations that disrupt the patterning of individual somites have dramatic effects on these tissues, including fusions of the ribs and vertebrae. The T-box transcription factor, Tbx6, is expressed in the paraxial mesoderm but is downregulated as somites develop. It is essential for the formation of posterior somites, which are replaced with ectopic neural tubes in Tbx6-null mutant embryos. We show that partial restoration of Tbx6 expression in null mutants rescues somite development, but that rostrocaudal patterning within them is defective, ultimately resulting in rib and vertebral fusions, demonstrating that Tbx6 activity in the paraxial mesoderm is required not simply for somite specification but also for their normal patterning. Somite patterning is dependent upon Notch signaling and we show that Tbx6 genetically interacts with the Notch ligand,delta-like 1 (Dll1). Dll1 expression, which is absent in theTbx6-null mutant, is restored at reduced levels in the partially rescued mutants, suggesting that Dll1 is a target of Tbx6. We also identify the spontaneous mutation rib-vertebrae as a hypomorphic mutation in Tbx6. The similarity in the phenotypes we describe here and that of some human birth defects, such as spondylocostal dysostosis,raises the possibility that mutations in Tbx6 or components of this pathway may be responsible for these defects.
Dally regulates Dpp morphogen gradient formation in theDrosophilawing
Authors: Fujise Momoko , Takeo Satomi , Kamimura Keisuke , Matsuo Takashi , Aigaki Toshiro , Izumi Susumu , Nakato Hiroshi
Published: March 2003

Decapentaplegic (Dpp), a Drosophila TGFβ/bone morphogenetic protein homolog, functions as a morphogen to specify cell fate along the anteroposterior axis of the wing. Dpp is a heparin-binding protein and Dpp signal transduction is potentiated by Dally, a cell-surface heparan sulfate proteoglycan, during assembly of several adult tissues. However, the molecular mechanism by which the Dpp morphogen gradient is established and maintained is poorly understood. We show evidence that Dally regulates both cellular responses to Dpp and the distribution of Dpp morphogen in tissues. In the developing wing, dally expression in the wing disc is controlled by the same molecular pathways that regulate expression of thickveins,which encodes a Dpp type I receptor. Elevated levels of Dally increase the sensitivity of cells to Dpp in a cell autonomous fashion. In addition,dally affects the shape of the Dpp ligand gradient as well as its activity gradient. We propose that Dally serves as a co-receptor for Dpp and contributes to shaping the Dpp morphogen gradient.
An I47L substitution in the HOXD13 homeodomain causes a novel human limb malformation by producing a selective loss of function
Authors: Caronia Giuliana , Goodman Frances R. , McKeown Carole M. E. , Scambler Peter J. , Zappavigna Vincenzo
Published: March 2003

The 5′ members of the Hoxa and Hoxd gene clusters play major roles in vertebrate limb development. One such gene, HOXD13, is mutated in the human limb malformation syndrome synpolydactyly. Both polyalanine tract expansions and frameshifting deletions in HOXD13 cause similar forms of this condition, but it remains unclear whether other kinds of HOXD13mutations could produce different phenotypes. We describe a six-generation family in which a novel combination of brachydactyly and central polydactyly co-segregates with a missense mutation that substitutes leucine for isoleucine at position 47 of the HOXD13 homeodomain. We compared the HOXD13(I47L) mutant protein both in vitro and in vivo to the wild-type protein and to an artificial HOXD13 mutant, HOXD13(IQN), which is completely unable to bind DNA. We found that the mutation causes neither a dominant-negative effect nor a gain of function, but instead impairs DNA binding at some sites bound by wild-type HOXD13. Using retrovirus-mediated misexpression in developing chick limbs, we showed that wild-type HOXD13 could upregulate chick EphA7in the autopod, but that HOXD13(I47L) could not. In the zeugopod, however,HOXD13(I47L) produced striking changes in tibial morphology and ectopic cartilages, which were never produced by HOXD13(IQN), consistent with a selective rather than generalised loss of function. Thus, a mutant HOX protein that recognises only a subset of sites recognised by the wild-type protein causes a novel human malformation, pointing to a hitherto undescribed mechanism by which missense mutations in transcription factors can generate unexpected phenotypes. Intriguingly, both HOXD13(I47L) and HOXD13(IQN)produced more severe shortening in proximal limb regions than did wild-type HOXD13, suggesting that functional suppression of anterior Hox genes by more posterior ones does not require DNA binding and is mediated by protein:protein interactions.
The effect of confirmation bias and racial stereotypes on perceptions of guilt and interrogation strategy decisions
Authors: Brimbal Laure , Atkinson Dominick J. , Meissner Christian A.
Published: January 2024

We examined whether racial stereotypes and guilt bias could affect perceptions of suspects and decisions in investigations. In three studies, participants read about a case, provided guilt judgments, and suggested questions they would ask a suspect. In all studies we manipulated race‐based stereotypes and guilt bias using different methods and operationalizations to provide a robust test of our hypotheses. In Experiment 1, we found that participants asked more guilt‐presumptive questions to the subject they decided was guilty. In Experiment 2, we found that when presented with more incriminating evidence, participants perceived suspects as more guilty and chose/generated more guilt‐presumptive questions. In Experiment 3, we found that those with less incriminating evidence reported lower levels of guilt and chose more coercive techniques. Our findings highlight the complexity of racial stereotypes and confirmation bias within investigation decision‐making.
Development of the American College of Rheumatology Patient‐Reported Outcome Quality Measures for Systemic Lupus Erythematosus
Authors: Katz Patricia P. , Barber Claire E. H. , Duarte‐García Alí , Garg Shivani , Machua Wambui , Rodgers Wendy , Santiago‐Casas Yesenia , Suter Lisa , Bartels Christie M. , Yazdany Jinoos
Published: January 2024

Objective

As part of a Centers for Disease Control and Prevention–funded American College of Rheumatology (ACR) initiative, we sought to develop quality measures related to Patient Reported Outcome Measure (PROM) use for systemic lupus erythematosus (SLE) clinical care.

Methods

An expert workgroup composed of physician, patient, and researcher representatives convened to identify patient‐reported outcome (PRO) domains of greatest importance to people with SLE. A patient advisory panel separately ranked domains. PROMs assessing priority domains were identified through structured literature review, and detailed psychometric reviews were conducted for each PROM. In a Delphi process, the expert workgroup rated PROMs on content validity, psychometric quality, feasibility of implementation, and importance for guiding patient self‐management. The patient advisory panel reviewed PROMs in parallel and contributed to the final recommendations.

Results

Among relevant PRO domains, the workgroup and patient partners ranked depression, physical function, pain, cognition, and fatigue as high‐priority domains. The workgroup recommended at least once yearly measurement for (1) assessment of depression using the Patient Health Questionnaire or Patient Reported Outcomes Measurement Information System (PROMIS) depression scales; (2) assessment of physical function using PROMIS physical function scales or the Multi‐Dimensional Health Assessment Questionnaire; and (3) optional assessments of fatigue and cognition. Pain scales evaluated were not found to be sufficiently superior to what is already assessed in most SLE clinic visits.

Conclusion

Expert workgroup members and patient partners recommend that clinicians assess depression and physical function at least once yearly in all people with SLE. Additional PROMs addressing cognition and fatigue can also be assessed. Next steps are to incorporate PROM‐based quality measures into the ACR The Rheumatology Informatics System for Effectiveness registry.
Reservoir Microneedle Patch Mitigates Postsurgical Atrial Fibrillation
Authors: Wang Wenshuo , Chen Yansong , Huang Liqi , Lu Ziyi , Ullah Muhammad Asad , Wei Lai , Yang Guang
Published: January 2024

Oral amiodarone for 3–6 months is commonly required for the prevention and treatment of atrial fibrillation (AF) after surgical ablation of refractory AF. However, clinical data show that oral administration is likely to cause systemic toxicity, especially pulmonary fibrosis. Here, a new strategy is described for the treatment and prevention of postsurgical AF via the epicardial application of a monolithic reservoir microneedle device. These findings demonstrate that this strategy enables a sustained transport of amiodarone directly to the atrium, thereby maximizing therapeutic efficacy and minimizing systemic drug distribution. Notably, a significantly reduced drug dosage (only one dose of 6.3 mg for reservoir MNs versus a daily dose of ≈10 mg for oral administration) achieves therapeutic efficacy over a long period of 24 weeks in a rat AF model, circumventing the risks of pulmonary fibrosis associated with oral administration. This device can serve as a promising alternative to oral amiodarone, providing a robust therapeutic strategy for the prevention and treatment of postsurgical AF is antipicated.
Fast Ion Transport Interphase Integrated with Space Confinement Enabling High‐Rate and Long‐Lifespan Na Metal Batteries
Authors: Xia Shuixin , Fan Wenxuan , Hou Zhen , Li Chenrui , Jiang Zongyan , Yang Junhe , Mao Jianfeng , Zheng Shiyou
Published: January 2024

The practical application of sodium (Na) metal anode has been seriously hindered by the uncontrolled Na dendrite growth and severe volume expansion inducing short battery lifespan and safety concerns. Here, highly sodiophilic and ultrafine ZnS‐modified carbon fibers have been rationally constructed as a scaffold to obviate these drawbacks. The in situ generated Na2S‐reinforced fast ion transport interphase and the effective space confinement synergistically facilitate the fast sodium ion interfacial transfer and the homogeneous and dendrite‐free Na deposition, thus enabling high‐rate and dendrite‐free Na metal anode. The modified Na metal demonstrates ultrahigh rate capability (15 mA cm−2) and ultralong cycling life (5300 cycles). Moreover, the Na|Na3V2(PO4)3 (NVP) cell delivers ultrahigh rate capability (80 C) and extraordinarily ultralong lifespan cycling durability (2980 cycles). The Na|NVP pouch cell also exhibits an extraordinarily ultralong‐term cycle life of over 1070 cycles with an extremely low capacity decay rate of 0.0088% per cycle at 10 C. This work provides a facile and efficient strategy to propel the Na metal anode towards practicability.
Material and Device Design of Flexible Perovskite Solar Cells for Next‐Generation Power Supplies
Authors: Tian Ruijia , Zhou Shujing , Meng Yuanyuan , Liu Chang , Ge Ziyi
Published: January 2024

This review outlines the rapid evolution of flexible perovskite solar cells (f‐PSCs) to address the urgent need for alternative energy sources, highlighting their impressive power conversion efficiency, which increases from 2.62% to over 24% within a decade. The unique optoelectronic properties of perovskite materials and their inherent mechanical flexibilities instrumental in the development of f‐PSCs are examined. Various strategies proposed for material modification and device optimization significantly enhance efficiency and bending durability. The transition from small‐scale devices to large‐area photovoltaic modules for diverse applications is discussed in addition to the challenges and innovative solutions related to film uniformity and environmental stability. This review provides succinct yet comprehensive insights into the development of f‐PSCs, paving the way for their integration into various applications and highlighting their potential in the renewable energy landscape.