A simulation study on the US rehabilitation service process for patients with modest-to-severe traumatic brain injury

Traumatic brain injury (TBI) is a devastating injury with severe consequences. In this paper, we conduct a simulation study on the commonly implemented care delivery process for TBI rehabilitation in the US, which covers three care categories: inpatient acute, outpatient sub-acute and general residential care. Our investigation is focused on assessing how coverage duration of publicly funded rehabilitation impacts two key system outcomes: sub-acute rehabilitation readmission and total rehabilitation spending. We develop prediction models on the above two outcomes for patients of different conditions. We introduce the notions of forceful transition and medical necessity adjustment, and embed the notions in a state-transition simulation model. Our simulation results suggest that to minimise the care spending, the duration of publicly insured outpatient sub-acute rehab be set smaller than what is currently implemented but not to the point where coverage should be completely removed. Our sensitivity analysis justifies the robustness of our results under variations on model parameters.     

珍珠层粉/壳聚糖多孔支架的制备及分析测试

用负压真空冷冻干燥机在-20℃条件下冷冻干燥48h制备珍珠层粉/壳聚糖复合多孔支架。用扫描电子显微镜(SEM)观察支架表面形貌,通过X射线衍射分析(XRD)、傅里叶红外光谱(FTIR)等手段对材料进行表征测试,检测其降解性能,并将兔骨髓间充质干细胞与支架共培养检测材料细胞毒性。结果表明复合支架具有稳固的三维多孔结构,孔隙率最大至91.64%,孔径在100~300μm范围,降解性能适宜,且冷冻干燥制备方法对珍珠层粉的结构无明显破坏,并具有良好的生物相容性,有利于细胞的生长。     

壳聚糖改性竹粉/PVC复合材料的制备和性能

壳聚糖、竹粉和PVC等按一定比例混合,用挤出成型法制备了竹粉/PVC复合材料。考察了壳聚糖添加量对复合材料物理力学性能、热稳定性、防水性能和防腐性能的影响。结果表明,适量壳聚糖的添加,可以改善复合材料的综合性能。且当壳聚糖含量为3wt%时复合材料的性能最佳,与未添加壳聚糖的复合材料相比,其拉伸强度、冲击强度和弯曲强度分别提高了44.7%、58.2%和79.6%,腐蚀前8天的吸水率从2.2%降低为1.6%,被白腐菌和褐腐菌腐蚀后材料的质量损失率分别降低了94.1%和75.0%。     

FRC measurement in intensive care patients. A definition of standards

Determination of Functional Residual Capacity (FRC) can be performed through washout methods, indicator gas dilution or bodyplethysmography. Some of these techniques have been adapted for use in intensive care patients whilst being mechanically ventilated. However, most measurement setups are bulky, cumbersome to use and their running costs are high. Hence FRC measurement has not become a routine method in intensive care although it offers considerable advantages in the management of ventilated patients such as the determination of "best PEEP", the detection of progressive alveolar collapse in the course of acute lung injury and during weaning from mechanical ventilation. Up to now most efforts to improve and simplify FRC measurement were made at the expense of accuracy. An ideal method ought to be accurate, easy to handle and cost-effective. It should supply not only FRC data but also information about intrapulmonary gas distribution and dead space. These demands can be met using modern data acquisition software. The pros and cons of all methods available for FRC measurement are discussed in view of their suitability for intensive care patients. A conventional nitrogen washout using emission spectroscopy for measurement of nitrogen concentration gives satisfying exact values for the determination of the parameters mentioned above. The measurement error can be lowered under 5% by special corrections for flow and nitrogen signal (delay and rise times, changes of gas viscosity). For flow measurement a normal pneumotachograph can be used. Using a laptop computer for data acquisition the bed-side monitor fulfills most of the demands in intensive care. It is then also possible to measure indices of intrapulmonary gas distribution such as Alveolar Mixing Efficiency and Lung Clearance Index.     

Isolation and characterization of a monoclonal anti-quadruplex DNA antibody from autoimmune "viable motheaten" mice

A cell line that produces an autoantibody specific for DNA quadruplex structures has been isolated and cloned from a hybridoma library derived from 3-month-old nonimmunized autoimmune, immunodeficient "viable motheaten" mice. This antibody has been tested extensively in vitro and found to bind specifically to DNA quadruplex structures formed by two biologically relevant sequence motifs. Scatchard and nonlinear regression analyses using both one- and two-site models were used to derive association constants for the antibody-DNA binding reactions. In both cases, quadruplexes had higher association constants than triplex and duplex molecules. The anti-quadruplex antibody binds to the quadruplex formed by the promoter-region-derived oligonucleotide d(CGCG4GCG) (Ka = 3.3 x 10(6) M-1), and has enhanced affinity for telomere-derived quadruplexes formed by the oligonucleotides d(TG4) and d(T2G4T2G4T2G4T2G4) (Ka = 5.38 x 10(6) and 1.66 x 10(7) M-1, respectively). The antibody binds both types of quadruplexes but has preferential affinity for the parallel four-stranded structure. In vitro radioimmunofilter binding experiments demonstrated that purified anti-DNA quadruplex antibodies from anti-quadruplex antibody-producing tissue culture supernatants have at least 10-fold higher affinity for quadruplexes than for triplex and duplex DNA structures of similar base composition and length. The antibody binds intramolecular DNA triplexes formed by d(G4T3G4T3C4) and d(C4T3G4T3G4), and the duplex d(CGCGCGCGCG)2 with an affinities of 6. 76 x 10(5), 5.59 x 10(5), and 8.26 x 10(5) M-1, respectively. Competition experiments showed that melted quadruplexes are not effective competitors for antibody binding when compared to native structures, confirming that the quadruplex is bound structure-specifically. To our knowledge, this is the first immunological reagent known to specifically recognize quadruplex structures. Subsequent sequence analysis demonstrates homologies between the antibody complementarity determining regions and sequences from Myb family telomere binding proteins, which are hypothesized to control cell aging via telomeric DNA interactions. The presence of this antibody in the autoimmune repertoire suggests a possible linkage between autoimmunity, telomeric DNA binding proteins, and aging.     

Percutaneous effects of iodine inhibit the development of experimental silicosis

Experiments on white rats proved that the silicotic pulmonary changes slowed with the tails periodically immersed into iodine solution. Those pulmonary changes were due to inhalation of quartzite dust and especially due to intratracheal administration of standardized quartz dust DQ12. Influenced by inhalation of dust containing quartz, the rats demonstrated characteristic alterations in cytologic features of bronchial and alveolar lavage water. The "iodine baths" also declined those alterations, that may prove higher resistance of pulmonary macrophages to cytotoxic effects of quartz. This hypothesis finds a support in experiments with culture of rat peritoneal macrophages. If incubated in a medium with low iodine concentrations and subsequently washed off, the macrophages demonstrate lower incidence of cytotoxic effects due to the next incubation with particles of DQ12. The macrophage's higher resistance against cytotoxic agents is believed to result directly in antisilicotic effect of iodine, so "iodine baths" could be recommended for pathogenetic therapy and medical prophylaxis of silicosis.     

The levels of memory (CD45RA-, RO+) CD4+ and CD8+ peripheral blood T-lymphocytes correlate with IgM rheumatoid factors in rheumatoid arthritis

We investigated whether, in rheumatoid arthritis (RA), the CD45 isoform expression of peripheral blood T-lymphocytes (T-PBL) is related to auto-immune processes (e.g. IgM rheumatoid factors) and to clinical manifestations. By three-colour flow cytometry, we quantified three subsets of CD4+ or CD8+ T-PBL: "naive" CD45RA+,RO-, "transient" CD45RA+,RO+, and "memory" CD45RA-,RO+ cells, in 102 patients with RA and in 41 age- and sex-matched controls. The serum levels of rheumatoid factors (RF) were determined--besides conventional agglutination tests--by ELISA (IgM-RF). Extensive clinical examination was performed at the time of blood sampling. In RA, age, sex and drug therapy did not constitute major influences on the CD45RA/RO patterns. In "healthy" men, higher age significantly' correlated with fewer naive and more memory CD4+ T-PBL (P < 0.01). In RA, distinct correlations between the T-PBL subsets, autoimmune and clinical manifestations became obvious when patients with low and high levels of RF against human IgG Fc fragments, as determined by ELISA, were analysed separately. RA patients with high IgM-RF had elevated proportions of CD45RO+ T-PBL (P < 0.05), that correlated with clinical parameters of disease activity (tender joint count, Ritchie index, P < 0.05) and outcome (Health Assessment Questionnaire, Larsen radiographic scores, P < 0.05). The proportions of memory CD4+ and CD8+ T-PBL correlated strongly (P < 0.001) with the IgM-RF levels. Within 1 year, only three of 34 patients (disease duration of 5-9 years) showed seroconversion from low to high levels of IgM-RF (and positive agglutination tests); this was paralleled by reductions in naive and increases in transient T-PBL (P < 0.02). Thus, in RA, the proportions of memory CD4+ and CD8+ T-PBL correlate with the level of IgM-RF and, together with transient T-PBL, with clinical parameters of disease activity and outcome.     

Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: comparison of different clearance techniques

RATIONALE AND OBJECTIVES: We wanted to improve determination of the glomerular filtration rate (GFR) with plasma clearance techniques because the alternative-renal clearance techniques-may involve inaccurate urine sampling or risk of urinary tract infection when bladder catheterization becomes necessary. Therefore, we compared the renal and plasma clearances of iohexol and chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), as well as endogenous creatinine clearance, in 19 normal pigs using different techniques. METHODS: After an intravenous bolus injection of the GFR markers, 16 plasma samples were used to plot the marker concentrations versus time for 4.5 hr. Urine was collected during nine 30-min periods. Plasma clearance was calculated by dividing the dose of marker with the area under the plasma concentration curve (AUC) from the time of injection to infinity using one-compartment (ClAUC-slope) and three-compartment (ClAUC-3comp) models. The renal clearance was calculated by dividing the amount of marker excreted in the urine in a period with the AUC in the same period. This AUC was determined by integrating the total area in the period (Clren adv)--our reference method representing the "true" GFR--or by using the arithmetic mean of the plasma concentrations of the marker at the beginning and end of the urine collection period (Clren simple). Creatinine clearance was determined according to Clren simple. RESULTS: Renal clearances of iohexol and 51Cr-EDTA were significantly higher than creatinine clearance (P = .0002). There was no significant difference between the renal clearances of iohexol and 51Cr-EDTA or between their plasma clearances. The two mathematical methods of calculating the renal clearance of iohexol were highly correlated (rs = .99), as were the two methods of calculating its plasma clearance (rs = .95). Because of the extrarenal clearance of the markers, the plasma clearance methods for iohexol and 51Cr-EDTA always overestimated the true GFR. ClAUC-3comp was the method closest to the true GFR. For iohexol, the median overestimation of the GFR was higher with ClAUC-slope when early plasma samples (30-120 min) after injection of the marker were used (5.5 ml.min-1.10 kg-1) than when late samples (180-270 min) were used (4.0 ml.min-1.10 kg-1). After subtracting the median extrarenal clearances of iohexol and 51Cr-EDTA (previously determined in nephrectomized pigs) from their plasma clearances (ClAUC-3comp), the median overestimation of the true GFR was reduced from 2.0 to 1.1 ml.min-1.10 kg-1 with iohexol and from 2.1 to 1.3 ml.min-1.10 kg-1 with 51Cr-EDTA. CONCLUSION: GFR determination with plasma clearance techniques can be improved in three- and one-compartment models by taking late plasma samples and by subtracting the extrarenal plasma clearance of the species. One-compartment models can be improved by determining a correction formula in the species for the early parts of the decay curve of the plasma concentration of the marker.     

Structure and evolutionary implications of a "cysteine-rich" Campoletis sonorensis polydnavirus gene family

For successful parasitization, the female Campoletis sonorensis endoparasitic wasp injects a polydnavirus into its host, Heliothis virescens, during oviposition. Viral gene expression induces immunosuppression and alters development of the host. We report here that three abundantly expressed genes, VHv1.1, WHv1.0, and WHv1.6, describes a polydnavirus "cysteine-rich" gene family which may be important in inducing these host manifestations. These genes have a similar primary gene structure and their proteins contain cysteine motifs characteristic of snail ion-channel ligands, the omega-conotoxins. Like the omega-conotoxins, the intercysteine amino acid residues are hypervariable with only three identical amino acids in all motifs. The conservation of this domain in the three viral genes may reflect an important functional role for these viral proteins in the parasitization of H. virescens. The three genes also contain introns similar in sequence at comparable positions in their 5' untranslated leaders and coding sequences. VHv1.1 contains two cysteine motifs, and each motif is interrupted by an intron at the same position as in the cysteine motifs of WHv1.0 and WHv1.6. Intron 2 sequences of WHv1.0 and WHv1.6 are 92% identical, while the immediately flanking exon sequences encoding the cysteine motifs are only 76% identical. This provides an example of nuclear pre-mRNA introns which are more conserved than flanking exons among members of a gene family.