Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects.

A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes.     

The Bermuda offshore market in transition

In summary, the Bermuda insurance industry is undergoing a major upheaval, with the ultimate outcome being presently unclear. However, offshore markets have been at the forefront of innovation in international insurance for the past decade, and this innovation is likely to continue. The successful companies of the future will take full advantage of the regulatory and accounting freedoms offered in Bermuda, the Cayman Islands, and other Caribbean locations. In the end, the offshore captive industry could well be transformed into an offshore specialty insurance market. The players will be fewer, but the business volume may be larger than ever.     

新生小猪脑含氧量和O-酪氨酸在双侧颈动脉结扎和失血中的变化

采用小猪双侧颈动脉结扎伴失血模型检测双侧颈动脉的结扎伴失血对脑氧分压和O-酪氨酸变化的影响,结果发现小猪脑氧分压为(51±4)托.颈动脉结扎和失血后60min降为(10±1.5)托(P<0.001),当颈动脉恢复通畅和失血再灌注后,脑氧分压增至(40±6)托,此值与预试验时的脑氧分压无明显差异.对照组中脑纹状体中的O-酪氨酸的含量为(0.57±0.19)nmoles/g组织.缺血试验后1h其含量明显升为(29±0.5)nmoles/g组织(P<0.005),显示缺血后再灌注导致脑纹状体O-酪氨酸显著上升.提示组织中羟基产生增加,可能与新生小猪脑缺血和再灌注损伤有一定作用.     

Polymères thiocarboxyliques, 5. Synthèse de poly(oxyéthylène)s à fonction dithioester terminale. Application au traitement de cellules d'électrophorèse

Poly(oxyethylene)s with dithioster end groups were obtained from mono- and dihydroxyl terminated commercial polymers by reaction with dimethyl chloroacetamide, subsequent thionation of the amide group, and usual conversion of the thioamides into the dithioesters 14, 15 and 20, 21 . The best results were obtained in the syntheses of the S-carboxymethyl dithioesters ( 15 and 21 ). The resulting reactive poly(oxyethylene)s were grafted upon silica tubes and electrophoresis cells, previously activated by aminopropylsilanization. These graftings result in lowering of the surface potential of the tubes and in suppression of the electro-osmosis flow in an electrophoresis cell tested with a TiO₂ standard sample.     

Successful treatment of acute head and neck dog bite wounds without antibiotics

Dog bites continue to be the most common bite injury in the United States. We previously reported a series of 61 patients with 215 dog bite wounds. Of these, 55 patients had 188 dog bite wounds of the head and neck area which were treated with copious saline pressure irrigation, meticulous wound and wound edge debridement, repeated copious saline pressure irrigation, adequate antibiotic coverage, wound closure, and close postoperative monitoring. A wound infection rate of .53% and a patient infection rate of 1.8% were obtained using this protocol. Our present study uses the same protocol with the exclusion of antibiotic coverage. Our series of 49 patients with 145 head and neck wounds reveals a wound infection rate of 1.4% and a patient infection rate of 4%. This is not statistically significantly different from the outcome of the previous study.     

In vivo anti-melanoma activities of the Melan-A/MART-1101–115 T CD4+ cell peptide

Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth.     

Early Results of the Mau Osteotomy for Correction of Moderate to Severe Hallux Valgus: A Review of 24 Cases

In our retrospective study, we report the objective results of the Mau osteotomy in the treatment of hallux valgus. We reviewed the results of 24 cases of moderate to severe hallux valgus deformities corrected with the Mau osteotomy of the first metatarsal combined with a distal soft-tissue procedure. Follow-up was possible in 24 cases. Preoperatively the mean hallux valgus and first intermetatarsal angles were 31.3 degrees and 16.6 degrees respectively, and were corrected postoperatively to an average of 13.00 degrees+/-7.15 degrees and 9.80 degrees+/-2.43 degrees respectively (P< .001). In the sagittal plane, the first metatarsal was shortened by an average of 2.00 mm. Two (8.3%) cases had dorsal elevation of the osteotomy fragment. Complications included 3 recurrences of the deformity, 1 frank nonunion, 8 dorsal cortical nonunions, 5 cases of undercorrection, and 1 case of broken hardware that was present in the nonunion that went on to revision. There were no superficial or deep infections, and no cases of transfer metatarsalgia were noted. In this series, the use of an oblique first metatarsal osteotomy with a dorsal shelf resulted in reliable and powerful correction of the first intermetatarsal angle in patients with moderate to severe hallux valgus. Particular attention should be paid to severe IM angles and the possibility of undercorrections. Despite ambulation postoperatively, the Mau osteotomy minimized dorsal malunion and the incidence of transfer metatarsalgia. LEVEL OF CLINICAL EVIDENCE: 4.     

CNS 7056: A Novel Ultra-short-acting Benzodiazepine

Background: A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo.

Methods: The affinity of CNS 7056 and its carboxylic acid metabolite, CNS 7054, for benzodiazepine receptors and their selectivity profiles were evaluated using radioligand binding. The activity of CNS 7056 and midazolam at subtypes ([alpha]1[beta]2[gamma]2, [alpha]2[beta]2[gamma]2, [alpha]3[beta]2[gamma]2, [alpha]5[beta]2[gamma]2) of the [gamma]-aminobutyric acid type A (GABAA) receptor was evaluated using the whole cell patch clamp technique. The activity of CNS 7056 at brain benzodiazepine receptors in vivo was measured in rats using extracellular electrophysiology in the substantia nigra pars reticulata. The sedative profile was measured in rodents using the loss of righting reflex test.

Results: CNS 7056 bound to brain benzodiazepine sites with high affinity. The carboxylic acid metabolite, CNS 7054, showed around 300 times lower affinity. CNS 7056 and CNS 7054 (10 [mu]m) showed no affinity for a range of other receptors. CNS 7056 enhanced GABA currents in cells stably transfected with subtypes of the GABAA receptor. CNS 7056, like midazolam and other classic benzodiazepines, did not show clear selectivity between subtypes of the GABAA receptor. CNS 7056 (intravenous) caused a dose-dependent inhibition of substantia nigra pars reticulata neuronal firing and recovery to baseline firing rates was reached rapidly. CNS 7056 (intravenous) induced loss of the righting reflex in rodents. The duration of loss of righting reflex was short (< 10 min) and was inhibited by pretreatment with flumazenil.     

Comparison between traditional 2-dimensional cephalometry and a 3-dimensional approach on human dry skulls.

The cephalogram is the standard used by orthodontists to assess skeletal, dental, and soft tissue relationships. This approach, however, is based on 2-dimensional (2D) views used to analyze 3-dimensional (3D) objects. The purpose of this project was to evaluate and compare a 3D imaging system and traditional 2D cephalometry for accuracy in recording the anatomical truth as defined by physical measurements with a calibrated caliper. Thirteen skeletal landmarks were located by both radiographic methods on 9 dry human skulls. Intraclass correlation (0.995), variance (0.054 mm(2)), and standard deviation (SD) (0.237 mm) were averaged over 76 measurements and derived from precision calipers to establish these physical measurements as a reliable gold standard to make comparisons of the 2D and 3D radiographic methods. The results showed great variability of the 2D from the gold standard, with the range varying from -17.68 mm (underestimation of Gn-Zyg R) to +15.52 mm (overestimation of Zyg L-Zyg R). In contrast, the 3D method (Sculptor, Glendora, Calif) indicated a range of the SD from -3.99 (underestimation) mm to +2.96 mm (overestimation). The 3D evaluation was much more precise, within approximately 1 mm of the gold standard. These results indicate that, when the actual distance is measured on a human skull in its true dimensions of 3D space, the Sculptor program, by using a 3D method, is more precise and 4 to 5 times more accurate than the 2D approach. Evaluating distances in 3D space with a 2D image grossly exaggerates the true measure and offers a distorted view of craniofacial growth. There is an inherent problem of representing a linear measure occupying a 3D space with a 2D image.