Enhanced Uridine Bioavailability Following Administration of a Triacetyluridine-Rich Nutritional Supplement

Uridine is a therapy for hereditary orotic aciduria and is being investigated in other disorders caused by mitochondrial dysfunction, including toxicities resulting from treatment with nucleoside reverse transcriptase inhibitors in HIV. Historically, the use of uridine as a therapeutic agent has been limited by poor bioavailability. A food supplement containing nucleosides, NucleomaxX®, has been reported to raise plasma uridine to supraphysiologic levels

Molecular Phylogenetics of the Genus Neoconocephalus (Orthoptera, Tettigoniidae) and the Evolution of Temperate Life Histories

BACKGROUND:The katydid genus Neoconocephalus (25+ species) has a prominent acoustic communication system and occurs in large parts of the Neotropics and Nearctic. This group has been subject of numerous behavioral, physiological, and evolutionary studies of its acoustic communication system. Two distinct life histories occur in this group: The tropical life history incorporates multiple generations/year and direct egg development without environmental triggers. Temperate life history is characterized by overwintering in the egg stage, cold trigger of egg development, and one generation/year. This study reconstructs the phylogenetic relationships within the genus to (1) determine the evolutionary history of the temperate life history, and (2) to support comparative studies of evolutionary and physiological problems in this genus. METHODOLOGY/PRINCIPAL FINDINGS:We used Amplified Fragment Length Polymorphisms (AFLP), and sequences of two nuclear loci and one mitochondrial locus to reconstruct phylogenetic relationships. The analysis included 17 ingroup and two outgroup species. AFLP and mitochondrial data provided resolution at the species level while the two nuclear loci revealed only deeper nodes. The data sets were combined in a super-matrix to estimate a total evidence tree. Seven of the temperate species form a monophyletic group; however, three more temperate species were placed as siblings of tropical species. CONCLUSIONS/SIGNIFICANCE:Our analyses support the reliability of the current taxonomic treatment of the Neoconocephalus fauna of Caribbean, Central, and North America. Ancestral state reconstruction of life history traits was not conclusive, however at least four transitions between life histories occurred among our sample of species. The proposed phylogeny will strengthen conclusions from comparative work in this group

Intraoperative radiation therapy (IORT) for previously untreated malignant gliomas

BACKGROUND: Intraoperative radiation therapy (IORT) is one of the methods used to deliver a large single dose to the tumor tissue while reducing the exposure of normal surrounding tissue. However, the usefulness of intraoperative electron therapy for malignant gliomas has not been established. METHODS: During the period from 1987 to 1997, 32 patients with malignant gliomas were treated with IORT. The histological diagnoses were anaplastic astrocytoma in 11 patients and glioblastoma in 21 patients. Therapy consisted of surgical resection and intraoperative electron therapy using a dose of 12–15 Gy (median, 15 Gy). The patients later underwent postoperative external radiation therapy (EXRT) with a median total dose of 60 Gy. Each of the 32 patients treated with IORT was randomly matched with patients who had been treated with postoperative EXRT alone (control). Patients were matched according to histological grade, age, extent of tumor removal, and tumor location. RESULTS: In the anaplastic astrocytoma group, the one-, two- and five-year survival rates were 81%, 51% and 15%, respectively in the IORT patients and 54%, 43% and 21%, respectively in the control patients. In the glioblastoma group, one-, two- and five-year survival rates were 63%, 26% and 0%, respectively in the IORT patients and 70%, 18% and 6%, respectively in the control patients. There was no significant difference between survival rates in the IORT patients and control patients in either the anaplastic astrocytoma group or glioblastoma group. CONCLUSIONS: IORT dose not improve survival of patients with malignant gliomas compared to that of patients who have received EXRT alone

A System for the Synchronized Recording of Sonomyography, Electromyography and Joint Angle

Ultrasound and electromyography (EMG) are two of the most commonly used diagnostic tools for the assessment of muscles. Recently, many studies reported the simultaneous collection of EMG signals and ultrasound images, which were normally amplified and digitized by different devices. However, there is lack of a systematic method to synchronize them and no study has reported the effects of ultrasound gel to the EMG signal collection during the simultaneous data collection. In this paper, we introduced a new method to synchronize ultrasound B-scan images, EMG signals, joint angles and other related signals (e.g. force and velocity signals) in real-time. The B-mode ultrasound images were simultaneously captured by the PC together with the surface EMG (SEMG) and the joint angle signal. The deformations of the forearm muscles induced by wrist motions were extracted from a sequence of ultrasound images, named as Sonomyography (SMG). Preliminary experiments demonstrated that the proposed method could reliably collect the synchronized ultrasound images, SEMG signals and joint angle signals in real-time. In addition, the effect of ultrasound gel on the SEMG signals when the EMG electrodes were close to the ultrasound probe was studied. It was found that the SEMG signals were not significantly affected by the amount of the ultrasound gel. The system is being used for the study of contractions of various muscles as well as the muscle fatigue

Evolution of Novel Signal Traits in the Absence of Female Preferences in Neoconocephalus Katydids (Orthoptera, Tettigoniidae)

Background Significance: Communication signals that function to bring together the sexes are important for maintaining reproductive isolation in many taxa. Changes in male calls are often attributed to sexual selection, in which female preferences initiate signal divergence. Natural selection can also influence signal traits if calls attract predators or parasitoids, or if calling is energetically costly. Neutral evolution is often neglected in the context of acoustic communication. Methodology/Principal Findings: We describe a signal trait that appears to have evolved in the absence of either sexual or natural selection. In the katydid genus Neoconocephalus, calls with a derived pattern in which pulses are grouped into pairs have evolved five times independently. We have previously shown that in three of these species, females require the double pulse pattern for call recognition, and hence the recognition system of the females is also in a derived state. Here we describe the remaining two species and find that although males produce the derived call pattern, females use the ancestral recognition mechanism in which no pulse pattern is required. Females respond equally well to the single and double pulse calls, indicating that the derived trait is selectively neutral in the context of mate recognition. Conclusions/Significance: These results suggest that 1) neutral changes in signal traits could be important in the diversification of communication systems, and 2) males rather than females may be responsible for initiating signa

Beyond the Cost of Price Adjustment: Investments in Pricing Capital

Abstract The literature on costs of price adjustment has long argued that changing prices is a complex and costly process. In fact, some authors have suggested that we should think of firms' price-setting activities as "producing" prices, similar to the way firms use production processes to produce goods and services. In this paper we explore one natural extension of this view, that besides observing costs of price adjustment, we should also expect to see firm-level investments in capital expenditures into these "pricing" production processes. We coin the term "pricing capital" for these investments, and suggest that they can improve the efficiency of the "pricing production" activities by both reducing the costs of adjusting prices, and improving the effectiveness of price adjustments in future periods. Using two types of data sources, we find compelling evidence of the existence as well as the importance of pricing capital in firms. The existence of firm-level "pricing capital" has the potential of fundamentally altering the way we think about pricing and price adjustment in many areas of economics. It suggests looking toward the "pricing capital" to decipher the likely degree and causes of price rigidity and its variation across price setters, markets, and industries. Moreover, "pricing capital" introduces a new, higher-level, pricing decision made by individual firms. Decisions to invest in pricing capital compete with traditional capital investment decisions that have long been studied in economics, such as capital investments in plant, equipment, and R&D. Furthermore, since pricing capital is a choice variable, it implies that costs of price adjustment often used in models of price rigidity are endogenous. As such, pricing capital offers new insights into the micro-foundations of the costs of price adjustment. The most provocative implication of the new theory of pricing, however, is that the allocative efficiency of the price system itself may be determined endogenously by individual price setters who choose whether and how much to invest in pricing capital.

Barriers to the provision of smoking cessation assistance:A qualitative study among Romanian family physicians

BACKGROUND: Smoking cessation is the most effective intervention to prevent and slow down the progression of several respiratory and other diseases and improve patient outcomes. Romania has legislation and a national tobacco control programme in line with the World Health Organization Framework for Tobacco Control. However, few smokers are advised to quit by their family physicians (FPs). AIM: To identify and explore the perceived barriers that prevent Romanian FPs from engaging in smoking cessation with patients. METHODS: A qualitative study was undertaken. A total of 41 FPs were recruited purposively from Bucharest and rural areas within 600 km of the city. Ten FPs took part in a focus group and 31 participated in semistructured interviews. Analysis was descriptive, inductive and themed, according to the barriers experienced. RESULTS: Five main barriers were identified: limited perceived role for FPs; lack of time during consultations; past experience and presence of disincentives; patients' inability to afford medication; and lack of training in smoking cessation skills. Overarching these specific barriers were key themes of a medical and societal hierarchy, which undermined the FP role, stretched resources and constrained care. CONCLUSIONS: Many of the barriers described by the Romanian FPs reflected universally recognised challenges to the provision of smoking cessation advice. The context of a relatively hierarchical health-care system and limitations of time and resources exacerbated many of the problems and created new barriers that will need to be addressed if Romania is to achieve the aims of its National Programme Against Tobacco Consumption

Yeasts associated with the production of distilled alcoholic beverages

Distilled alcoholic beverages are produced firstly by fermenting sugars emanating from cereal starches (in the case of whiskies), sucrose-rich plants (in the case of rums), fructooligosaccharide-rich plants (in the case of tequila) or from fruits (in the case of brandies). Traditionally, such fermentations were conducted in a spontaneous fashion, relying on indigenous microbiota, including wild yeasts. In modern practices, selected strains of Saccharomyces cerevisiae are employed to produce high levels of ethanol together with numerous secondary metabolites (eg. higher alcohols, esters, carbonyls etc.) which greatly influence the final flavour and aroma characteristics of spirits following distillation of the fermented wash. Therefore, distillers, like winemakers, must carefully choose their yeast strain which will be very important in providing the alcohol content and the sensory profiles of spirit beverages. This Chapter discusses yeast and fermentation aspects associated with the production of selected distilled spirits and highlights similarities and differences with the production of wine

Mystery Solved: The Identification of the Two Missing Romanov Children Using DNA Analysis

One of the greatest mysteries for most of the twentieth century was the fate of the Romanov family, the last Russian monarchy. Following the abdication of Tsar Nicholas II, he and his wife, Alexandra, and their five children were eventually exiled to the city of Yekaterinburg. The family, along with four loyal members of their staff, was held captive by members of the Ural Soviet. According to historical reports, in the early morning hours of July 17, 1918 the entire family along with four loyal members of their staff was executed by a firing squad. After a failed attempt to dispose of the remains in an abandoned mine shaft, the bodies were transported to an open field only a few kilometers from the mine shaft. Nine members of the group were buried in one mass grave while two of the children were buried in a separate grave. With the official discovery of the larger mass grave in 1991, and subsequent DNA testing to confirm the identities of the Tsar, the Tsarina, and three of their daughters – doubt persisted that these remains were in fact those of the Romanov family. In the summer of 2007, a group of amateur archeologists discovered a collection of remains from the second grave approximately 70 meters from the larger grave. We report forensic DNA testing on the remains discovered in 2007 using mitochondrial DNA (mtDNA), autosomal STR, and Y- STR testing. Combined with additional DNA testing of material from the 1991 grave, we have virtually irrefutable evidence that the two individuals recovered from the 2007 grave are the two missing children of the Romanov family: the Tsarevich Alexei and one of his sisters

Monitoring of Regulatory T Cell Frequencies and Expression of CTLA-4 on T Cells, before and after DC Vaccination, Can Predict Survival in GBM Patients

PURPOSE: Dendritic cell (DC) vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL) subsets in glioblastoma patients treated with DC vaccination at UCLA. EXPERIMENTAL DESIGN: Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival. RESULTS: The change in regulatory T cell (CD3(+)CD4(+)CD25(+)CD127(low)) frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623) after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+)CD4(+) T cells (p = 0.0191; hazard ratio = 2.840) and CD3(+)CD8(+) T cells (p = 0.0273; hazard ratio = 2.690), while that of activation markers (CD25, CD69) was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves. CONCLUSIONS: Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future prospective immunotherapy trials to further evaluate its predictive validity