Dose properties of x-ray beams produced by laser-wakefield-accelerated electrons

Given that laser wakefield acceleration (LWFA) has been demonstrated experimentally to accelerate electron beams to energies beyond 25 MeV, it is reasonable to assess the ability of existing LWFA technology to compete with conventional radiofrequency linear accelerators in producing electron and x-ray beams for external-beam radiotherapy. We present calculations of the dose distributions (off-axis dose profiles and central-axis depth dose) and dose rates of x-ray beams that can be produced from electron beams that are generated using state-of-the-art LWFA. Subsets of an LWFA electron energy distribution were propagated through the treatment head elements (presuming an existing design for an x-ray production target and flattening filter) implemented within the EGSnrc Monte Carlo code. Three x-ray energy configurations (6 MV, 10 MV and 18 MV) were studied, and the energy width deltaE of the electron-beam subsets varied from 0.5 MeV to 12.5 MeV. As deltaE increased from 0.5 MeV to 4.5 MeV, we found that the off-axis and central-axis dose profiles for x-rays were minimally affected (to within about 3%), a result slightly different from prior calculations of electron beams broadened by scattering foils. For deltaE of the order of 12 MeV, the effect on the off-axis profile was of the order of 10%, but the central-axis depth dose was affected by less than 2% for depths in excess of about 5 cm beyond d(max). Although increasing deltaE beyond 6.5 MeV increased the dose rate at d(max) by more than 10 times, the absolute dose rates were about 3 orders of magnitude below those observed for LWFA-based electron beams at comparable energies. For a practical LWFA-based x-ray device, the beam current must be increased by about 4-5 orders of magnitude.     

Septic Revision Total Knee Arthroplasty Is Associated With Significantly Higher Mortality Than Aseptic Revisions: Long-Term Single-Center Study (1254 Patients)

BackgroundThe aim of this study is to examine the differences in long-term mortality rates between septic and aseptic revision total knee arthroplasty (rTKA) in a single specialist center over 17-year period.MethodsRetrospective consecutive study of all patients who underwent rTKA at our tertiary center between 2003 and 2019 was carried out. Revisions were classified as septic or aseptic. We identified patients’ age, gender, American Society of Anesthesiologists grade, and body mass index. The primary outcome measure was all-cause mortality at 5 years, 10 years, and over the whole study period of 17 years. Death was identified through both local hospital electronic databases and linked data from the National Joint Registry/NHS Personal Demographic Service. Kaplan-Meier survival curves were used to estimate time to death.ResultsIn total, 1298 consecutive knee revisions were performed on 1254 patients (44 bilateral revisions) with 985 aseptic revisions in 945 patients (75.4%) and 313 septic revisions in 309 patients (24.6%). Average age was 70.6 years (range 27-95) with 720 females (57.4%). Septic revisions had higher mortality rates; patients’ survivorship for septic vs aseptic revisions was 77.6% vs 89.5% at 5 years, 68.7% vs 80.2% at 10 years, and 66.1% vs 75.0% at 17 years; these differences were all statistically significant (P < .0001). The unadjusted 10-year risk ratio of death after septic revision was 1.59 (95% confidence interval 1.29-1.96) compared to aseptic revisions.ConclusionrTKA performed for infection is associated with significantly higher long-term mortality at all time points compared with aseptic revision surgery.Level of EvidenceLevel IV.     

β1整合素基因缺失对Gi蛋白分布的影响

目的 了解跨膜蛋白β1整合素对信号分子G蛋白细胞内构型的影响,为进一步研究β1整合素在信号传导中的作用打下基础。方法 采用荧光双标记及重叠合显微镜分析技术,观察野生型胚胎干细胞系（D3细胞）,β1整合素基因敲除胚胎干细胞（G201细胞）,β1整合素基因敲除后再植入胚胎干细胞（G201N）及小鼠胚胎心肌细胞中多种G蛋白（Gas,Gai1-3,Gao,Gai/o/t/z）细胞内构型特点和差异。结果 Gas,Gao,Gai/o/t/z在上述几种细胞系中均呈弥温性分布,未能发现明显差异,与此不同的是Gai1-3在D3细胞源性心肌细胞内呈网状分布,在非心肌细胞内呈线条状分布,而在G201细胞中Gi上述特异性构型被打乱,呈近似于弥漫样分布,值得注意的是在β1整合素重新恢复的G201N细胞Gi构型又呈网样或线条样分布,与野生型胚胎干细胞中Gi的构型相一致。结论 β1整合素能够影响信号分子Gi蛋白的细胞内定位,推测β1整合素可通过改变Gi的分布而影响Gi介导的信号传导。     

Involvement of nitric oxide synthase in the physiology and pathophysiology of facial nerve function and dysfunction

To date few reports have discussed the presence and function of nitric oxide (NO) in structures of the facial nerve. We performed nicotinamide adenine dinucleotide phosphate (NADPH-d)-diaphorase-histochemistry and immunohistochemistry on the intratemporal portion of the facial nerve, including the geniculate ganglion, of guinea pigs using specific antibodies to the three known isoforms of NO synthase and soluble guanylyl-cyclase (sGC). Normal facial nerves were compared to those treated intratympanically with bacterial lipopolysaccharides (LPS) and tumor necrosis factor-α (TNF-α). Both constitutive NOS isoforms and sGC could be detected in the bipolar ganglion cells of normal animals, while the inducible isoform (iNOS or NOS II) was not found. Endothelial NOS (NOS III) and sGC were present in blood vessels and were predominantly found in the perineurial sheath and less in the endoneurium. sGC could be detected in all fibers in a cross section of the facial nerve. LPS and TNF treatment led to the detection of iNOS in the perikaryia of the geniculate ganglion and the perineural sheath. These findings imply that NO may be involved in neurotransmission at least in the visceroafferent system. NO regulates vascular tone of nutrient blood vessels in the perineural sheath and endoneurium. The presence of sGC indicates that NO acts via its second messenger cGMP. NOS II expression may be a contributing factor to facial nerve palsy via two different mechanisms: NOS II-generated NO may lead to an overstimulation of the visceroefferent nerve fibers and motor fibers of the facial nerve. Dysregulation in facial nerve blood vessels could lead to edema and elevated pressure on the nerve within its osseous canal. Received: 13 April 1999 / Accepted: 12 August 1999     

THE ROLE OF RAPID SLIDE CULTURE IN THE DIAGNOSIS AND MANAGEMENT OF PULMONARY TUBERCULOSIS

Rapid slide culture method using human blood medium was utilized for the primary culture of Mycobacterium tuberculosis and the results obtained were compared with results of smear examination of sputum specimens from fresh cases of pulmonary tuberculosis. Smear and rapid slide culture results of a total of 320 patients were analyzed. Slide culture was positive in 104 cases whereas smears were positive in 90 cases. Early culture confirmation in 7 days coupled with positivity better than smear examination, makes rapid slide culture a better method for diagnosis.KEY WORDS: Mycobacterium tuberculosis, Rapid slide culture, Bacteriological techniques, Colony count microbial     

Congenital NOS2 deficiency protects mice from LPS-induced hyporesponsiveness to inhaled nitric oxide

BACKGROUND: In animal models, endotoxin (lipopolysaccharide) challenge impairs the pulmonary vasodilator response to inhaled nitric oxide (NO). This impairment is prevented by treatment with inhibitors of NO synthase 2 (NOS2), including glucocorticoids and L-arginine analogs. However, because these inhibitors are not specific for NOS2, the role of this enzyme in the impairment of NO responsiveness by lipopolysaccharide remains incompletely defined. METHODS: To investigate the role of NOS2 in the development of lipopolysaccharide-induced impairment of NO responsiveness, the authors measured the vasodilator response to inhalation of 0.4, 4, and 40 ppm NO in isolated, perfused, and ventilated lungs obtained from lipopolysaccharide-pretreated (50 mg/kg intraperitoneally 16 h before lung perfusion) and untreated wild-type and NOS2-deficient mice. The authors also evaluated the effects of breathing NO for 16 h on pulmonary vascular responsiveness during subsequent ventilation with NO. RESULTS: In wild-type mice, lipopolysaccharide challenge impaired the pulmonary vasodilator response to 0.4 and 4 ppm NO (reduced 79% and 45%, respectively, P < 0.001), but not to 40 ppm. In contrast, lipopolysaccharide administration did not impair the vasodilator response to inhaled NO in NOS2-deficient mice. Breathing 20 ppm NO for 16 h decreased the vasodilator response to subsequent ventilation with NO in lipopolysaccharide-pretreated NOS2-deficient mice, but not in lipopolysaccharide-pretreated wild-type, untreated NOS2-deficient or untreated wild-type mice. CONCLUSIONS: In response to endotoxin challenge, NO, either endogenously produced by NOS2 in wild-type mice or added to the air inhaled by NOS2-deficient mice, is necessary to impair vascular responsiveness to inhaled NO. Prolonged NO breathing, without endotoxin, does not impair vasodilation in response to subsequent NO inhalation. These results suggest that NO, plus other lipopolysaccharide-induced products, are necessary to impair responsiveness to inhaled NO in a murine sepsis model.     

Lentiviral gene transfer to the nonhuman primate brain

Lentiviral vectors infect quiescent cells and allow for the delivery of genes to discrete brain regions. The present study assessed whether stable lentiviral gene transduction can be achieved in the monkey nigrostriatal system. Three young adult Rhesus monkeys received injections of a lentiviral vector encoding for the marker gene beta galatosidase (beta Gal). On one side of the brain, each monkey received multiple lentivirus injections into the caudate and putamen. On the opposite side, each animal received a single injection aimed at the substantia nigra. The first two monkeys were sacrificed 1 month postinjection, while the third monkey was sacrificed 3 months postinjection. Robust incorporation of the beta Gal gene was seen in the striatum of all three monkeys. Stereological counts revealed that 930,218; 1,192,359; and 1,501,217 cells in the striatum were beta Gal positive in monkeys 1 (n = 2) and 3 (n = 1) months later, respectively. Only the third monkey had an injection placed directly into the substantia nigra and 187,308 beta Gal-positive cells were identified in this animal. The injections induced only minor perivascular cuffing and there was no apparent inflammatory response resulting from the lentivirus injections. Double label experiments revealed that between 80 and 87% of the beta Gal-positive cells were neurons. These data indicate that robust transduction of striatal and nigral cells can occur in the nonhuman primate brain for up to 3 months. Studies are now ongoing testing the ability of lentivirus encoding for dopaminergic trophic factors to augment the nigrostriatal system in nonhuman primate models of Parkinson's disease.     

Use of GEE for modeling censored correlated data: application to the study of risk factors for withdrawal of totally implantable vascular access devices in cystic fibrosis

BACKGROUND: The proportional hazards model proposed by Cox for modeling censored data is not suited for correlated delays, for instance when several events can be observed on each subject. METHODS: To analyze correlated delays, we propose to use a log-linear marginal model equivalent to Cox model. Correlations are taken into account through the use of Liang and Zeger's Generalized Estimating Equations (GEE) and of their robust variance estimator. An advantage of this method is that it can be implemented through the SAS GENMOD procedure. When ties are observed, we propose to use multiple imputations, creating M data sets without ties from the original one. RESULTS: This method is applied to a retrospective survey on the risk of withdrawing totally implantable vascular access devices (TIVAD) because of complication in cystic fibrosis patients: 265 TIVAD implanted in 200 patients were observed. Risk factors were characteristics of the device or of the patient. Results obtained with the robust variance estimator and ten imputations show that the use of the device for taking blood (vs exclusive perfusion of antibiotics), polyurethane catheter (vs. silicon), use of counterpressure for upkeeping and pulmonary colonization by Pseudomonas Aeruginosa are significantly associated to withdrawal. Under the Cox model which does not account for the correlations, some conclusions differ because the robust variance of the estimators is smaller than the variance obtained under the working assumption of independent delays. CONCLUSION: This approach allows the modeling of correlated survival data with SAS software. Our results illustrate the necessity of accounting for existing correlations.     

Successful chemotherapeutic treatment of diencephalic syndrome with continued tumor presence

A 7-month-old infant with typical features of diencephalic syndrome (DES) associated with a hypothalamic mass, most probably a glioma, was treated with chemotherapy. The tumor showed clear shrinkage, but after more than 2 years regrowth was noted. During the treatment period the child regained normal growth and became free of symptoms. As radiation therapy, especially at a young age, has significant adverse effects and a neurosurgical approach to the diencephalic region also has the potential to cause significant sequelae, a chemolherapeulic option, when it exists, is preferred. Thus, in an infant in whom a glioma is suspected to be the cause of the DES, based on the clinical picture and the neuroimaging appearance, chemotherapy should be considered the primary therapeutic modality. Even if its effect is temporary, its use is well justified. The most appropriate treatment protocol still needs to be determined.