A Novel Framework for Ab Initio Coarse Protein Structure Prediction.

Hydrophobic-Polar model is a simplified representation of Protein Structure Prediction (PSP) problem. However, even with the HP model, the PSP problem remains NP-complete. This work proposes a systematic and problem specific design for operators of the evolutionary program which hybrids with local search hill climbing, to efficiently explore the search space of PSP and thereby obtain an optimum conformation. The proposed algorithm achieves this by incorporating the following novel features: (i) new initialization method which generates only valid individuals with (rather than random) better fitness values; (ii) use of probability-based selection operators that limit the local convergence; (iii) use of secondary structure based mutation operator that makes the structure more closely to the laboratory determined structure; and (iv) incorporating all the above-mentioned features developed a complete two-tier framework. The developed framework builds the protein conformation on the square and triangular lattice. The test has been performed using benchmark sequences, and a comparative evaluation is done with various state-of-the-art algorithms. Moreover, in addition to hypothetical test sequences, we have tested protein sequences deposited in protein database repository. It has been observed that the proposed framework has shown superior performance regarding accuracy (fitness value) and speed (number of generations needed to attain the final conformation). The concepts used to enhance the performance are generic and can be used with any other population-based search algorithm such as genetic algorithm, ant colony optimization, and immune algorithm.

A Review of Protein Structure Prediction Using Lattice Model.

The prediction of the tertiary structure of a protein from its primary sequence is a long-standing problem for life science researchers. Solutions to this problem have a direct impact on other research areas such as design and discovery of new drugs, understanding the sequenced genomic data, solving the puzzle of protein structure, and understanding the folding mechanism. Solving protein structure prediction (PSP) is considered a cornerstone for life science research to reveal the mechanism of cellular processes; it has been an open problem for past six decades. Globally, various research institutes are working toward a solution to PSP with different methods. In this paper, we present a review of de novo PSP using hydrophobic-polar lattice model. In the hydrophobic-polar model, the PSP problem is defined as a combinatorial optimization problem with an objective of finding the protein structure having the lowest free energy. This study is bounded to two key factors. The first is application of the evolutionary search algorithms for PSP, and the second is the evolution of the modeling method and its corresponding potential energy function. The goal of this paper is to give sufficient biological background to understand the fundamentals of proteins, their structure, and available computational methods.

A Comparative Study on Single and Multiple Point Crossovers in a Genetic Algorithm for Coarse Protein Modeling.

The protein structure prediction problem is a holy grail for life science researchers. Computational protein structure prediction involves the folding of protein sequence (string) into the tertiary structure, called the native protein structure. The hydrophobic polar (HP) model is one of the basic models used to investigate the protein folding mechanism at the coarse level. In the HP model, the protein structure prediction problem is defined as an optimization problem, where the protein sequence must be folded over a lattice space such that the protein structure exhibits the lowest value of free energy. However, with the HP model, protein structure prediction is a nondeterministic polynomial (NP)-complete problem and is, therefore, simulated using meta-heuristic algorithms. Simulation of the HP model results in the formation of various protein structures called protein conformations. In this article, we present a case study on the application of a genetic algorithm to simulate the HP model based protein structure prediction. In this work, we employ the two versions of crossover functions (single-point vs. multiple-point crossovers) to generate protein conformations. The conformations were assessed based on the presence of hydrophobic contacts identified in the experimental structure. The sensitivity, specificity, and accuracy of simulation algorithm (genetic algorithm) were compared, and the significance of the parameters was statistically evaluated using the paired t-test. Our results indicate that the multipoint crossover operator enhanced the performance of genetic algorithm compared to genetic algorithm with single-point crossover. Also, multipoint crossover reduced the generation of false conformations, which results in a significant reduction in computational cost.

Electron conductive three-dimensional polymer of cuboidal C60.

Single crystals of three-dimensional (3D) C60 polymer were prepared by the topotactic conversion of two-dimensional (2D) C60 polymer single crystals at a pressure of 15 GPa at 600 degrees C. The x-ray single crystal study revealed that the 3D C60 polymer crystallized in a body centered orthorhombic space group Immm, and spherical C60 monomer units were substantially deformed to rectangular parallelepiped (cuboidal) shapes, each unit being bonded to eight cuboidal C60 neighbors via [3 + 3] cycloaddition. The 3D C60 polymer was electron conductive, in contrast with the nonconductive behavior of 2D polymers.

Inpatient care for uncomplicated bronchiolitis: comparison with Milliman and Robertson guidelines.

CONTEXT: Bronchiolitis is the most common lower respiratory tract infection in infancy. A recent Centers for Disease Control and Prevention report confirmed that hospitalization rates for bronchiolitis have increased 2.4-fold from 1980 to 1996. Controversies exist about optimal treatment plans. Milliman and Robertson recommend ambulatory care management; in case of hospitalization, the recommended length of stay is 1 day. OBJECTIVES: To relate actual practice variation for infants admitted with uncomplicated bronchiolitis to Milliman and Robertson's recommendations. DESIGN: Prospective observational study. SETTING: General care wards of 8 pediatric hospitals of the Child Health Accountability Initiative during the winter of 1998-1999. PATIENTS: First-time admissions for uncomplicated bronchiolitis in patients not previously diagnosed as having asthma and who were younger than 1 year. MAIN OUTCOME MEASURES: Respiratory rate, monitored interventions, attainment of discharge criteria goals, and length of stay. RESULTS: Eight hundred forty-six patients were included in the final analysis: 85.7% were younger than 6 months, 48.5% were nonwhite, and 64.1% were Medicaid recipients or self-pay. On admission to the hospital, 18.3% of the infants had respiratory rates higher than higher than 80 breaths per minute, 53.8% received supplemental oxygen therapy, and 52.6% received intravenous fluids. These proportions decreased to 1.9%, 33.8%, and 20.3%, respectively, 1 day after admission, and to 0.7%, 20.1%, and 8.6%, respectively, 2 days after admission. The average length of stay was 2.8 days (SD, 2.3 days). CONCLUSIONS: Milliman and Robertson's recommendations do not correspond to practice patterns observed at the hospitals participating in this study; no hospital met the Milliman and Robertson recommended 1-day goal length of stay. Administration of monitored intervention persisted past the second day of hospitalization.

Behind the scences of a collaborative.

The Child Health Accountability Initiative, a rapid-improvement collaborative for pediatrics, has learned valuable lessons about forming and sustaining the alliance.

Urban Wisconsin pediatric patients using an after-hours telephone triage service: outcomes and compliance.

OBJECTIVE: Evaluate the ability of a telephone triage service (TTS) to assess illness acuity of and patient compliance with advice given. DESIGN: Retrospective, observational study. PATIENTS: Patients of an urban, academic, pediatric clinic whose parents or caregivers called the TTS between July 23, 1997 and August 23, 1997. OUTCOME MEASURES: Patient outcomes and visit information at related medical encounters subsequent to a TTS call. RESULTS: Patients were primarily African-American, under age 5, enrolled in a Medicaid HMO, and most often called for fever, HMO authorization, or asthma. Homecare and PED referrals were the two most frequent dispositions; overall compliance rate was 60%. No patient referred for non-emergent care required care on an urgent or emergent basis. CONCLUSIONS: Initial results suggest that the TTS can effectively evaluate illness acuity in an urban population and compliance with advice is reasonable. A TTS may offer significant benefits to ensure care quality and contain costs in this population.

Serum neuron-specific enolase as a predictor of intracranial lesions in children with head trauma: a pilot study.

OBJECTIVE: To determine the reliability of serum neuron-specific enolase (NSE) levels in predicting intracranial lesions (ICL) in children with blunt head trauma (HT). METHODS: A prospective pilot study was conducted of patients 0 to 18 years of age presenting to a children's hospital emergency department (ED) between December 1997 and October 1998. Children presenting within 24 hours of injury who required head computed tomography (CT) were eligible. Blood samples were obtained to measure serum NSE level. Data collected included patient demographics, historical information, Glasgow Coma Scale score (GCS), physical examination, head CT results, and outcome. Patients were assigned to one of two groups based on the head CT results (PICL; presence of intracranial lesion, or NICL; no intracranial lesion). Data were analyzed using Student's t-test and chi-square. The 95% confidence interval (95% CI) was calculated when appropriate. A receiver operating characteristic curve was constructed to determine the NSE level that yielded the highest sensitivity and specificity for predicting ICL. RESULTS: Fifty patients were enrolled; 22 (45%) had abnormal head CT. No difference in demographics or mechanism of injury was observed between those with abnormal or normal CT scans. The mean GCS level was 11.9 +/- 4.2 for PICL and 13.9 +/- 2.6 for NICL (p = 0.045; 95% CI = -0.05 to -3.9). The mean NSE level was 26.7 +/- 21.4 for PICL and 17.7 +/- 7.8 for NICL (p = 0.048; 95% CI = 0.1 to 17.9). An NSE level > or = 15.3 ng/mL yielded a sensitivity of 77%, a specificity of 52%, and a negative predictive value of 74%. CONCLUSIONS: These results suggest that serum NSE may be a useful screening tool for predicting ICL in children with blunt head trauma. However, the NSE alone was neither sensitive nor specific in predicting all patients with ICL.

A randomized clinical trial of dermal anesthesia by iontophoresis for peripheral intravenous catheter placement in children.

STUDY OBJECTIVE: To assess the efficacy of dermal anesthesia by lidocaine iontophoresis in children undergoing peripheral intravenous (PIV) catheter placement in the emergency department. METHODS: A double-blind, randomized, clinical trial was conducted at a tertiary children's hospital ED. Alert children 7 years or older requiring nonemergency PIV were eligible. Patients in the lidocaine group received 1 mL of 2% lidocaine with 1:100,000 epinephrine over a potential PIV site by iontophoresis. The control group received 1 mL of.9% saline solution with 1:100,000 epinephrine. After PIV placement, patients ranked the procedural pain using a visual analog scale. Complications were noted by visual inspection or telephone follow-up. RESULTS: During a 6-month period, 22 patients were assigned to the lidocaine group and 25 to the control group. There was no significant difference in age, sex, or ethnic background between the 2 study groups, and mean application time was 12.0 minutes. The median pain score was.5 in the lidocaine group compared with 4 in the control group (P =.0002; 95% confidence interval [CI] 1 to 5). No significant immediate or delayed complications were observed. CONCLUSION: Lidocaine iontophoresis provides effective dermal anesthesia for children older than 7 years of undergoing nonemergency PIV placement in the ED.

Psychosocial aspects of child abuse for primary care pediatricians.

Childhood is an image that advertisers use to conjure up feelings of care-free innocence. Society frequently calls for protecting our children and creating strong, healthy families. Yet thousands of children experience violence on a regular basis, and their lives are irretrievably altered. For these children, the sites of violence and not war-torn villages or crime-ridden streets but their own homes. This article provides primary care physicians with basic information about the psychosocial aspects of recognition and prevention of child abuse.

Evaluation for possible physical or sexual abuse.

In summary, child abuse requires a multidisciplinary approach. The clinician's role in obtaining the history and physical examination demands that one be familiar with interview technique, appropriate developmental milestones, normal genital anatomy, and the use of local community resources. Knowing that there are circumstances when the examination should be deferred to a specialized center or done under anesthesia is critical. Determining that a reasonable suspicion of abuse exists is the job of the clinician. The final determination of abuse is under the purview of the legal system.

Nonurgent use of the pediatric emergency department during the day.

OBJECTIVE: To evaluate the pattern and reasons for nonurgent use of the pediatric emergency department (PED) during regular office hours and why primary care physicians (PCP) approve such visits. DESIGN: Prospective, cross-sectional, observational study. SETTING: Free-standing, university-affiliated children's hospital emergency department. PATIENTS: Patients presenting to the PED and triaged as nonurgent between June and November 1994, Monday through Friday from 6:30 am to 6:30 pm, and Saturday 6:30 am to 12:00 noon. MEASUREMENTS: Registration and triage information and all communication with the PCP. RESULTS: Of 1020 eligible patients, 364 patients and their PCP completed the study. Fifty-two percent of the study patients were enrolled in a health maintenance organization (HMO). This is consistent with the penetration of managed care in this community. Most HMO (118 of 191, 62%) and non-HMO enrollees (147 of 173, 86%) did not call their PCP prior to arrival in the PED. Comparing the reasons given by these patients (HMO enrollees versus non-HMO) for not calling, we found: convenience (HMO 17% vs non-HMO 4%, P < 0.01), "no identified PCP" (HMO 17% vs non-HMO 42%, P < 0.01), and "felt problem was an emergency" (HMO 19% vs non-HMO 10%, P = 0.03) to be important differences. HMO enrollees received approval for the visit 79% of the time. These approvals were mostly after noon, whereas most denials occurred before noon. We found a pattern in the reason for approvals. Before 3:30 pm, the most common reason was that the PCP "considered the problem medically urgent" (48 out of 106). After 3:30 pm, without significant difference in the pattern of patient's chief complaints, there was a dramatic change to "a full office schedule" (25 out of 45) as the most common reason. CONCLUSION: Communication between the patient and PCP prior to the PED visit is poor in the study population. Convenience and physician workload appear to be important factors in the choice to use the PED for nonurgent problems.

The Whiplash Shaken Infant Syndrome: has Caffey's syndrome changed or have we changed his syndrome?

OBJECTIVE: The aim of this study is to examine the data used by John Caffey in his description of the Whiplash Shaken Infant Syndrome and compare it with recent data in an attempt to determine whether the syndrome that he described has changed, or if we have changed his syndrome into what we now call The Shaken Infant Syndrome. METHOD: This study examined recent literature describing the Shaken Infant Syndrome, and compared it to Caffey's descriptions. In addition, a retrospective review of 71 children under the age of 3 years identified as having a subdural hematoma caused by other than accidental means during 54 months was done. This data was compared to data from the 27 case examples offered by Caffey in 1972 and his other descriptions in 1974 and 1946. RESULTS: A review of recent literature shows that our definition of Shaken Infant Syndrome today includes cases where impact trauma was involved. In contrast to Caffey's descriptions, we found the perpetrator to be more often male, fractures to be more often to ribs rather than long bones, and admissions of shaking and other trauma more often made. CONCLUSIONS: Our findings demonstrate that not only have we changed the diagnostic parameters from Caffey's original Whiplash Shaken Infant Syndrome, but the syndrome has also changed to reflect changes in medical diagnosis and in our society.

Implications of managed care denials for pediatric inpatient care.

With the growing penetration of managed care into the healthcare market, providers continue to experience increasing cost constraints. In this environment, it is important to track reimbursement denials and understand the managed care organization's rationale for refusal of payment. This is especially critical for providers of pediatric care, as children justifiably have unique healthcare needs and utilization patterns. We developed a system for tracking and documenting denials in our institution and found that health maintenance organizations denied claims primarily for one of three reasons: medically unnecessary care, care provided as a response to social (rather than medical) need, and provider inefficiencies. Health maintenance organization denials are also growing annually at our institutions. This knowledge can not only help providers of pediatric care more effectively negotiate future contracts, but provides an opportunity to differentiate the health needs of the pediatric patient from those of the adult. This information can be used as a basis for education, pediatric outcome studies, and guideline development--all tools that can help providers receive reasonable reimbursement for pediatric services and enable them to meet the complex health needs of children. Recommendations for action are discussed.

Evaluating child sexual abuse in the emergency department: clinical and behavioral indicators.

Child sexual abuse is an increasingly common problem. This article reviews the current clinical and behavioral indicators that will aid the emergency physician when evaluating and managing this condition. The most common differential diagnoses are described and a general approach to this diagnosis is suggested. Adopting a multidisciplinary method when evaluating this problem will lessen the anxiety facing the examining physician and provide a better outcome for the child, parents, and community.

Hypernatremic dehydration in breast-fed infants.

Three cases highlight the association between elevated breast milk sodium and hypernatremic dehydration in the infant. All three mothers, breast-feeding exclusively, had sodium levels in breast milk elevated significantly above normal. Severe hypernatremic dehydration in otherwise normal infants who are exclusively breast fed can be due to elevated sodium levels in breast milk.

Escherichia coli bacteremia in children. A review of 91 cases in 10 years.

We reviewed 91 cases of pediatric Escherichia coli bacteremia during a 10-year period. Thirty one patients were afebrile; a significantly greater proportion of these patients were aged less than 1 month, had ampicillin-resistant E coli isolates, or had persistent bacteremia 24 hours after initiating antibiotic therapy. Infection was community acquired in 65 cases; associated urinary tract infection was six times more common in this setting than in nosocomially acquired infections. In 85 cases at least 1 underlying medical condition/focus of infection was identified at the time the positive blood culture was obtained, the most common were immune deficiency states (38 cases), urinary tract infection (29 cases), and lesions of the gastrointestinal tract (27 cases). Polymicrobial bacteremia occurred in five cases. Twelve patients died; significantly associated with death were hypotension requiring pressor therapy, presence of a central venous catheter, and neutropenia.