Fibrin gels are attractive scaffolds useful for neural tissue engineering applications. The objective of this work was to investigate the apoptotic activity, survival, proliferation, and ...differentiation of a mixed population of primary neural cells composed of neurons and multipotent precursor cells when cultured in fibrin gels prepared with varying concentrations of fibrinogen (5-25 mg/mL fibrinogen) and thrombin (1-125 U/mL thrombin). Within all fibrin gel formulations tested, the level of apoptosis on day 1 was low and cell survival was equivalent to levels in monolayer culture (67%). Proliferation in gels made from 5 to 12.5 mg/mL fibrinogen was also similar to that observed in monolayer culture, though a lower proliferative response was observed in 25 mg/mL fibrinogen formulations. Relative to monolayer culture, cholinergic and dopaminergic neuronal presence was enhanced, whereas glial cell growth was reduced in fibrin gel cultures. The extent to which levels were altered depended on fibrinogen and thrombin concentration. The findings here suggest the importance of fibrinogen and thrombin concentration in differentially regulating the growth and composition of neural cell populations and are of importance for neural tissue engineering strategies focused on the development of implantable scaffolds for treating neurodegenerative disorders.
We evaluated clinical, radiographic, and short-term recovery outcomes in an 18-month 1 surgeon series of 102 unilateral primary total hip arthroplasties performed by direct lateral approach through ...standard size (15-20 cm) and limited (<10 cm) incisions. Patients were blinded to incision type. Observed measures related to hematological status, transfusions, operative time, hospitalization time, narcotic use, rehabilitation, and discharge disposition did not appear to differ by incision type. Components were well placed in both groups. Intraoperative femoral fractures occurred in 2 limited-incision cases. At 2 years' minimum follow-up, we did not observe evidence that minimally invasive surgical technique provided clinically significant benefit to these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Wear and osteolysis have been successfully treated by modular polyethylene exchange in revision hip arthroplasty. However, studies of the same approach in revision knee arthroplasty have not provided ...similar results. We evaluated the results of isolated polyethylene exchange for wear and/or osteolysis in 68 press-fit condylar TKAs from four centers. At a minimum of 24 months after polyethylene exchange surgery (average, 44 months; range, 24-83 months), there were 11 failures (16.2%). Failures included aseptic loosening in 10 knees and infection in one. With the relatively small cohort size we were unable to identify factors that predicted which knees were more likely to fail: we observed no correlation between failure and patient demographics, component design, or use of cement versus bone graft augmentation. Radiographic review demonstrated no progression of osteolytic lesions in 97% of knees in the study. While the short-term followup limits the conclusions, we believe the 84% success rate with modular polyethylene exchange for wear and osteolysis and the lack of progression of osteolytic lesions in the majority of the knees are encouraging. Full revision of well-fixed total knee components can lead to substantial bone loss, particularly in the face of osteolysis and we therefore consider modular polyethylene exchange in press-fit condylar knees a reasonable option for wear and osteolysis.
Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence
OBJECTIVE: Our purpose was to study prospectively the use of ultrasonographic biometry to refine the risk estimates for both Down syndrome and any clinically significant chromosome defect in women ...with abnormal biochemical triple-screen results. STUDY DESIGN: Ultrasonographic biometry and anatomic survey were performed on study and control cases. Expected values for humerus, femur, combined humerus plus femur lengths, and abdominal circumference were generated on the basis of biparietal diameter obtained from a normal group. Threshold observed/expected values of each measurement for screening for Down syndrome and clinically significant chromosome defects were determined with receiver-operator characteristic curves. By stepwise logistic regression analysis the optimal screening parameters, including nuchal thickness, for detection of Down syndrome and clinically significant chromosome defect were determined. Risk tables for chromosome anomalies were developed on the basis of ultrasonography and triple-screen values. RESULTS: Of 1034 cases at risk for Down syndrome (risk ≥1/270) or trisomy 18 on the basis of triple-screen results, there were 11 cases of Down syndrome, 1 of trisomy 18, and 17 clinically significant chromosome defects. Abnormal nuchal thickness or observed/expected humerus length <0.92 was the most sensitive parameter for Down syndrome detection. Abnormal nuchal thickness or observed/expected combined femur and humerus length <0.90 was the most sensitive for significant chromosome defects. With abnormal biometry or anatomy the Down syndrome risk was 8 of 127 versus 1 of 753 in normals, odds ratio 50.4 (95% confidence interval 6.4 to 90.2), p < 0.00001, and the risk of significant defects was 11 of 90 versus 6 of 830 in normals, odds ratio 19.3 (95% confidence interval 6.4 to 60.5), p < 0.00001. In a pregnancy with a 1 in 270 triple-screen risk for Down syndrome, normal biometric and anatomic results reduce the risk to 1 in 2100. CONCLUSION: Normal ultrasonographic anatomy and biometry significantly reduces the risk of both Down syndrome and any significant chromosome defects in pregnancies with abnormal triple-screen results. (Am J Obstet Gynecol 1996;175:824-9.)
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Daily rhythms in the timing of the preovulatory surge and the display of reproductive behavior are reversed in diurnal and nocturnal rodents, but little is known about the neural mechanisms ...underlying these differences. We examined this issue by comparing a diurnal murid rodent, Arvicanthis niloticus (the grass rat), to a nocturnal one, Rattus norvegicus (the lab rat). In the first study, we established that sequential estradiol and progesterone treatment induces a proestrous-like rise in LH secretion and in the percentage of GnRH neurons that express Fos in grass rats, as is the case in lab rats. Next, we tested the hypothesis that differences in the timing of estrus-related events in diurnal and nocturnal species are caused by differences in rhythms in responsiveness to steroid hormones. We found rhythms in GnRH neuron activity, as indicated by Fos, that were 12 hours out of phase in grass rats and lab rats. These patterns persisted in both species when animals were housed in constant darkness for 5 days, suggesting that they are driven by an endogenous circadian mechanism. These results indicate that steroid-primed grass rats and lab rats are similar with respect to the temporal relationship among estrus-related events, but that the timing of these events relative to the light-dark cycle is dramatically different and that this difference is caused by endogenous circadian mechanisms.
Objective To compare Down syndrome screening efficiency of the standard serum triple analyte screen to that of a four‐component screen consisting of ultrasound biometry and serum markers in the ...second trimester.
Methods The Down syndrome screening efficiency of the triple screen, i.e. alpha‐fetoprotein (AFP), unconjugated estriol (E3), hCG and maternal age, was compared with the four‐marker algorithm, i.e. humerus length, nuchal thickness, AFP and hCG plus maternal age. A quadrivariate Gaussian algorithm was used to calculate individual Down syndrome odds. Receiver operating characteristic (ROC) curves plotting sensitivity against false‐positive rate were constructed for each algorithm and the areas under the curves were compared to determine which was superior. Sensitivity and false‐positive rates at different Down syndrome risk thresholds were also compared.
Results There were 46 cases of Down syndrome (1.9%) with 2391 normal singleton pregnancies in a referral population in which triple screen, fetal biometry and karyotype had been done. The gestational age range for the study was 14–24 completed weeks. The median maternal age for the study group was 35.0 years (14.0–46.0 years). The areas (SE) under the ROC curves were 0.75(0.04) and 0.93(0.02) for the standard triple and the four‐marker screen, respectively (P < 0.001). At a 10% false‐positive rate, detection was 45.7% for the triple and 80.4% for the four‐marker screen.
Condusions A new algorithm combining humerus length and nuchal thickness measurement with serum AFP, hCG and maternal age substantially improved Down syndrome screening efficiency compared with the traditional triple screen. The model appears promising and should be evaluated in an independent data set.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The elaborate ornamental plumage displayed by birds has largely been attributed to sexual selection, whereby the greater success of ornamented males in attaining mates drives a rapid elaboration of ...those ornaments. Indeed, plumage elaboration tends to be greatest in species with a high variance in reproductive success such as polygynous mating systems. Even among socially monogamous species, many males are extremely colourful. In their now-classic study, Møller and Birkhead (1994) suggested that increased variance in reproductive success afforded by extra-pair paternity should intensify sexual selection pressure and thus an elaboration of male plumage and sexual dichromatism, but the relatively few measures of extra-pair paternity at the time prevented a rigorous test of this hypothesis. In the nearly three decades since that paper's publication, hundreds of studies have been published on rates of extra-pair paternity and more objective measures of plumage colouration have been developed, allowing for a large-scale comparative test of Møller and Birkhead's (1994) hypothesis. Using an analysis of 186 socially monogamous passerine species with estimates of extra-pair paternity, our phylogenetically controlled analysis confirms Møller and Birkhead's (1994) early work, demonstrating that rates of extra-pair paternity are positively associated with male, but not female, colouration and with the extent of sexual dichromatism. Plumage evolution is complex and multifaceted, driven by phylogenetic, ecological, and social factors, but our analysis confirms a key role of extra-pair mate choice in driving the evolution of ornamental traits.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transportation agencies are using a variety of rumble strip patterns to improve highway safety. Previous studies have documented the efficacy of rumble strips in reducing certain crash types. ...However, no research has been published on the operational effects of these low-cost safety treatments. An evaluation of the effect a treatment has on operational characteristics can be conducted and reported in much less time than an evaluation based on crash data. The effect of centerline rumble strips on lateral vehicle placement and vehicle speeds on two-lane highways was investigated with a before-and-after observational study. Data were collected using tape switches at two treatment sites and two comparison sites. The lane widths were 11 and 12 ft. Data analysis and statistical testing indicated the centerline rumble strips had a significant effect on the mean and variance of lateral vehicle placement at both treatment sites. The observed change in the mean lateral vehicle location was away from the centerline rumble strips at both treatment sites; the variance of lateral vehicle location decreased at both sites. Data collected at the corresponding comparison sites during the before-and-after periods indicated no change in the mean and variance of lateral vehicle placement. Additionally, the study found that lateral vehicle placement in travel lanes may not be normally distributed as was previously assumed. Further evaluation of lateral vehicle placement distribution should be conducted with larger sample sizes and different roadway cross sections. No relationship could be drawn between speed and the presence of rumble strips for 11- or 12-ft lanes.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Although bivalirudin compared with unfractionated heparin with glycoprotein IIb/IIIa inhibitors reduces bleeding and hospitalization costs in patients undergoing percutaneous coronary intervention ...(PCI), little is known about the economic impact of bivalirudin versus heparin alone and at what threshold of procedural bleeding risk bivalirudin would be considered cost-effective.
A validated model was used to predict risk of major bleeding for 81,628 National Cardiovascular Data Registry (NCDR) CathPCI Registry patients from 2004 to 2006 who received unfractionated heparin only. Costs were derived from multiple sources including wholesale acquisition costs (for drugs) and single-center data (for PCI-related complications). Based on ISAR-REACT 3, we assumed that bivalirudin would reduce the risk of major bleeding by 33% compared with unfractionated heparin alone. A Markov model was used to estimate lost life expectancy associated with a major bleed. Major bleeding was predicted to occur in 2.2% of patients. Bivalirudin for all patients was estimated to increase costs by $571 per patient, yielding cost-effectiveness ratios of $287,473 per bleeding event averted and $1,173,360 per quality-adjusted life-year gained. Bivalirudin was cost saving for patients with a predicted bleeding risk >20% (0.16% of CathPCI population). At willingness-to-pay thresholds of $50K and $100K per quality-adjusted life-year gained, bivalirudin was cost-effective for patients with a bleeding risk > or = 8% (2.5% patients) and > or = 5% (7.9% patients), respectively.
This decision-analytic modeling study demonstrates that for patients undergoing PCI, substitution of bivalirudin for unfractionated heparin monotherapy is projected to increase costs for virtually all patients and would be considered cost-effective for only a minority of patients with a high bleeding risk. From a policy standpoint, studies such as this, aimed at identifying the appropriate risk threshold for initiating treatment, may help in the development of informed guidelines for the use of expensive therapies.
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