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991.
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Jay G. Berry Annapurna Poduri Joshua L. Bonkowsky Jing Zhou Dionne A. Graham Chelsea Welch Heather Putney Rajendu Srivastava 《PLoS medicine》2012,9(1)
Background
Care advances in the United States (US) have led to improved survival of children with neurological impairment (NI). Children with NI may account for an increasing proportion of hospital resources. However, this assumption has not been tested at a national level.Methods and Findings
We conducted a study of 25,747,016 US hospitalizations of children recorded in the Kids'' Inpatient Database (years 1997, 2000, 2003, and 2006). Children with NI were identified with International Classification of Diseases, 9th Revision, Clinical Modification diagnoses resulting in functional and/or intellectual impairment. We assessed trends in inpatient resource utilization for children with NI with a Mantel-Haenszel chi-square test using all 4 y of data combined. Across the 4 y combined, children with NI accounted for 5.2% (1,338,590) of all hospitalizations. Epilepsy (52.2% [n = 538,978]) and cerebral palsy (15.9% [n = 164,665]) were the most prevalent NI diagnoses. The proportion of hospitalizations attributable to children with NI did not change significantly (p = 0.32) over time. In 2006, children with NI accounted for 5.3% (n = 345,621) of all hospitalizations, 13.9% (n = 3.4 million) of bed days, and 21.6% (US$17.7 billion) of all hospital charges within all hospitals. Over time, the proportion of hospitalizations attributable to children with NI decreased within non-children''s hospitals (3.0% [n = 146,324] in 1997 to 2.5% [n = 113,097] in 2006, p<.001) and increased within children''s hospitals (11.7% [n = 179,324] in 1997 to 13.5% [n = 209,708] in 2006, p<0.001). In 2006, children with NI accounted for 24.7% (2.1 million) of bed days and 29.0% (US$12.0 billion) of hospital charges within children''s hospitals.Conclusions
Children with NI account for a substantial proportion of inpatient resources utilized in the US. Their impact is growing within children''s hospitals. We must ensure that the current health care system is staffed, educated, and equipped to serve this growing segment of vulnerable children. Please see later in the article for the Editors'' Summary 相似文献995.
Trevor J. Morin Teresa J. Broering Brett A. Leav Barbra M. Blair Kirk J. Rowley Elisabeth N. Boucher Yang Wang Peter S. Cheslock Michael Knauber David B. Olsen Steve W. Ludmerer Gyongyi Szabo Robert W. Finberg Robert H. Purcell Robert E. Lanford Donna M. Ambrosino Deborah C. Molrine Gregory J. Babcock 《PLoS pathogens》2012,8(8)
Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412–423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, whereas a dose of 50 mg/kg HCV1 did not protect. In addition, an acutely-infected chimpanzee given 250 mg/kg HCV1 42 days following exposure to virus had a rapid reduction in viral load to below the limit of detection before rebounding 14 days later. The emergent virus displayed an E2 mutation (N415K/D) conferring resistance to HCV1 neutralization. Finally, three chronically HCV-infected chimpanzees were treated with a single dose of 40 mg/kg HCV1 and viral load was reduced to below the limit of detection for 21 days in one chimpanzee with rebounding virus displaying a resistance mutation (N417S). The other two chimpanzees had 0.5–1.0 log10 reductions in viral load without evidence of viral resistance to HCV1. In vitro testing using HCV pseudovirus (HCVpp) demonstrated that the sera from the poorly-responding chimpanzees inhibited the ability of HCV1 to neutralize HCVpp. Measurement of antibody responses in the chronically-infected chimpanzees implicated endogenous antibody to E2 and interference with HCV1 neutralization although other factors may also be responsible. These data suggest that human monoclonal antibody HCV1 may be an effective therapeutic for the prevention of graft infection in HCV-infected patients undergoing liver transplantation. 相似文献
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997.
Recently, Wu and colleagues [1] proposed two novel statistics for genome-wide interaction analysis using case/control or case-only data. In computer simulations, their proposed case/control statistic outperformed competing approaches, including the fast-epistasis option in PLINK and logistic regression analysis under the correct model; however, reasons for its superior performance were not fully explored. Here we investigate the theoretical properties and performance of Wu et al.'s proposed statistics and explain why, in some circumstances, they outperform competing approaches. Unfortunately, we find minor errors in the formulae for their statistics, resulting in tests that have higher than nominal type 1 error. We also find minor errors in PLINK's fast-epistasis and case-only statistics, although theory and simulations suggest that these errors have only negligible effect on type 1 error. We propose adjusted versions of all four statistics that, both theoretically and in computer simulations, maintain correct type 1 error rates under the null hypothesis. We also investigate statistics based on correlation coefficients that maintain similar control of type 1 error. Although designed to test specifically for interaction, we show that some of these previously-proposed statistics can, in fact, be sensitive to main effects at one or both loci, particularly in the presence of linkage disequilibrium. We propose two new "joint effects" statistics that, provided the disease is rare, are sensitive only to genuine interaction effects. In computer simulations we find, in most situations considered, that highest power is achieved by analysis under the correct genetic model. Such an analysis is unachievable in practice, as we do not know this model. However, generally high power over a wide range of scenarios is exhibited by our joint effects and adjusted Wu statistics. We recommend use of these alternative or adjusted statistics and urge caution when using Wu et al.'s originally-proposed statistics, on account of the inflated error rate that can result. 相似文献
998.
Small heat shock proteins and α-crystallins: dynamic proteins with flexible functions 总被引:1,自引:0,他引:1
The small heat shock proteins (sHSPs) and the related α-crystallins (αCs) are virtually ubiquitous proteins that are strongly induced by a variety of stresses, but that also function constitutively in multiple cell types in many organisms. Extensive research has demonstrated that a majority of sHSPs and αCs can act as ATP-independent molecular chaperones by binding denaturing proteins and thereby protecting cells from damage due to irreversible protein aggregation. As a result of their diverse evolutionary history, their connection to inherited human diseases, and their novel protein dynamics, sHSPs and αCs are of significant interest to many areas of biology and biochemistry. However, it is increasingly clear that no single model is sufficient to describe the structure, function or mechanism of action of sHSPs and αCs. In this review, we discuss recent data that provide insight into the variety of structures of these proteins, their dynamic behavior, how they recognize substrates, and their many possible cellular roles. 相似文献
999.
ABSTRACT: INTRODUCTION: Mycoplasma hominis brain abscess is a rare occurrence, and treatment is not well defined.The mechanism by which M. hominis infects sites outside the genitourinary tract, includingthe central nervous system, is unclear. CASE PRESENTATION: We report the case of a 40-year-old Somali man who sustained a traumatic brain injury thatrequired initial neurosurgical hematoma evacuation and that subsequently was complicatedby a hospital-acquired M. hominis brain abscess. Our patient was successfully treated withneurosurgical debridement and an antibiotic course of intravenous doxycycline. CONCLUSIONS: Head trauma or neurosurgical procedures or both might be a predisposing factor for this typeof infection. 相似文献
1000.
Two DCM mutants (E40K and E54K) of tropomyosin (Tm) were examined using the thin-filament extraction/reconstitution technique. The effects of the Ca2+, ATP, phosphate (Pi), and ADP concentrations on isometric tension and its transients were studied at 25°C, and the results were compared to those for the WT protein. Our results indicate that both E40K and E54K have a significantly lower T
HC (high Ca2+ tension at pCa 4.66) (E40K: 1.21±0.06 T
a, ±SEM, N = 34; E54K: 1.24±0.07 T
a, N = 28), a significantly lower T
LC (low- Ca2+ tension at pCa 7.0) (E40K: 0.07±0.02 T
a, N = 34; E54K: 0.06±0.02 T
a, N = 28), and a significantly lower T
act (Ca2+ activatable tension) (T
act = T
HC–TLC, E40K: 1.15±0.08 T
a, N = 34; E54K: 1.18±0.06 T
a, N = 28) than WT (T
HC = 1.53±0.07 T
a, T
LC = 0.12±0.01 T
a, T
act = 1.40±0.07 T
a, N = 25). All tensions were normalized to T
a ( = 13.9±0.8 kPa, N = 57), the tension of actin-filament reconstituted cardiac fibers (myocardium) under the standard activating conditions. The Ca2+ sensitivity (pCa50) of E40K (5.23±0.02, N = 34) and E54K (5.24±0.03, N = 28) was similar to that of the WT protein (5.26±0.03, N = 25). The cooperativity increased significantly in E54K (3.73±0.25, N = 28) compared to WT (2.80±0.17, N = 25). Seven kinetic constants were deduced using sinusoidal analysis at pCa 4.66. These results enabled us to calculate the cross-bridge distribution in the strongly attached states, and thereby deduce the force/cross-bridge. The results indicate that the force/cross-bridge is ∼15% less in E54K than WT, but remains similar to that of the WT protein in the case of E40K. We conclude that over-inhibition of the actomyosin interaction by E40K and E54K Tm mutants leads to a decreased force-generating ability at systole, which is the main mechanism underlying the early pathogenesis of DCM. 相似文献