A real-time intercepting beam-profile monitor for a medical cyclotron.

There is a lack of real-time continuous beam-diagnostic tools for medical cyclotrons due to high power deposition during proton irradiation. To overcome this limitation, we have developed a profile monitor that is capable of providing continuous feedback about beam shape and current in real time while it is inserted in the beam path. This enables users to optimize the beam profile and observe fluctuations in the beam over time with periodic insertion of the monitor.

Traumatic brain injury precipitates cognitive impairment and extracellular Aß aggregation in Alzheimer's disease transgenic mice.

Traumatic brain injury (TBI) has become a signature wound of the wars in Iraq and Afghanistan. Many American soldiers, even those undiagnosed but likely suffering from mild TBI, display Alzheimer's disease (AD)-like cognitive impairments, suggesting a pathological overlap between TBI and AD. This study examined the cognitive and neurohistological effects of TBI in presymptomatic APP/PS1 AD-transgenic mice. AD mice and non-transgenic (NT) mice received an experimental TBI on the right parietal cortex using the controlled cortical impact model. Animals were trained in a water maze task for spatial memory before TBI, and then reevaluated in the same task at two and six weeks post-TBI. The results showed that AD mice with TBI made significantly more errors in the task than AD mice without TBI and NT mice regardless of TBI. A separate group of AD mice and NT mice were evaluated neurohistologically at six weeks after TBI. The number of extracellular beta-amyloid (Aß)-deposits significantly increased by at least one fold in the cortex of AD mice that received TBI compared to the NT mice that received TBI or the AD and NT mice that underwent sham surgery. A significant decrease in MAP2 positive cells, indicating neuronal loss, was observed in the cortex of both the AD and NT mice that received TBI compared to the AD and NT mice subjected to sham surgery. Similar changes in extracellular Aß deposits and MAP2 positive cells were also seen in the hippocampus. These results demonstrate for the first time that TBI precipitates cognitive impairment in presymptomatic AD mice, while also confirming extracellular Aß deposits following TBI. The recognition of this pathological link between TBI and AD should aid in developing novel treatments directed at abrogating cellular injury and extracellular Aß deposition in the brain.

Treating dyspareunia caused by vaginal atrophy: a review of treatment options using vaginal estrogen therapy.

Vulvovaginal atrophy (VVA) and dryness are common symptoms of the decline in endogenous production of estrogen at menopause and often result in dyspareunia. Yet while 10% to 40% of women experience discomfort due to VVA, it is estimated that only 25% seek medical help. The main goals of treatment for vaginal atrophy are to improve symptoms and to restore vaginal and vulvar anatomic changes. Treatment choices for postmenopausal dyspareunia resulting from vulvovaginal atrophy will depend on the underlying etiology and might include individualized treatment. A number of forms of vaginal estrogen and manner of delivery are currently available to treat moderate to severe dyspareunia caused by VVA. They all have been shown to be effective and are often the preferred treatment due to the targeted efficacy for urogenital tissues while resulting in only minimal systemic absorption. Both healthcare professionals and patients often find it difficult to broach the subject of sexual problems associated with VVA. However, with minimal effort to initiate a conversation about these problems, healthcare providers can provide useful information to their postmenopausal patients in order to help them each choose the optimal treatment for their needs and symptoms.

Multiple-object tracking is based on scene, not retinal, coordinates.

This study tested whether multiple-object tracking-the ability to visually index objects on the basis of their spatiotemporal history-is scene based or image based. Initial experiments showed equivalent tracking accuracy for objects in 2-D and 3-D motion. Subsequent experiments manipulated the speeds of objects independent of the speed of the scene as a whole. Results showed that tracking accuracy was influenced by object speed but not by scene speed. This held true whether the scene underwent translation, zoom, rotation, or even combinations of all 3 motions. A final series of experiments interfered with observers' ability to see a coherent scene by moving objects at different speeds from one another and by distorting the perception of 3-D space. These reductions in scene coherence led to reduced tracking accuracy, confirming that tracking is accomplished using a scene-based, or allocentric, frame of reference.

Nicotine addiction: insights from recent animal studies.

RATIONALE: Recent preclinical behavioral and neurobiological research has characterized important behavioral features and has identified neurobiological substrates that may underlie nicotine reinforcement and addiction. OBJECTIVE: To examine recent advances on nicotine exposure in preclinical models, from three perspectives: (a) the chronopharmacokinetics of nicotine, (b) behavioral studies on nicotine reinforcement, withdrawal, and reinstatement/relapse, and (c) effects of nicotine on neurobiological substrates after repeated exposure. RESULTS: Preclinical studies can be used to operationally model selected aspects of nicotine reinforcement, withdrawal, and reinstatement or relapse. These may be used to investigate the functional in vivo consequences of acute and long-term changes in neuronal acetylcholine receptor populations that follow nicotine exposure. Behavioral studies focusing on distinct stages of nicotine exposure (e.g., active reinforcement vs. cessation or reinstatement) may also be used in parallel with studies on dopaminergic function, a proposed substrate for the reinforcing effects of nicotine, and of opioid receptor function, a possible site of neuroadaptations secondary to nicotine exposure. CONCLUSIONS: While no single current animal model may capture the experience of human smoking or nicotine addiction, increasingly, separate animal models are capturing the full spectrum of behavioral and neurobiological dimensions of this complex condition.

Substance dependence posttraumatic stress disorder therapy. An integrated cognitive-behavioral approach.

While substance abuse and posttraumatic stress disorder (PTSD) are known to frequently co-occur, there have been few published clinical trials evaluating integrated approaches for this form of dual diagnosis. This article describes Substance Dependence PTSD Therapy (SDPT), the first manualized individual treatment to undergo a controlled clinical trial. SDPT is a 5-month, twice-weekly, two-phase individual cognitive-behavioral treatment utilizing (a) relapse prevention and coping skills training for substance abuse; and (b) psychoeducation, stress inoculation training, and in vivo exposure for PTSD. SDPT is also unique in having been designed for use in mixed-gendered civilians with varied sources of trauma. Design considerations and the format, structure, and content of therapy sessions are discussed. Open trial pilot data indicates efficacy in reducing PTSD severity.

Intra-Operative Analysis of Scoliosis Surgery in 3-D.

Scoliosis is a three-dimensional deformity characterized by coronal, sagittal and axial rotation of the spine. Surgical fusion of the spine is required in severe cases. Assessment of the surgical procedure requires enough accuracy and flexibility to allow planning of individual interventions or implant designs. Conventional 2-D radiography and even 3-D CT scanning have limitations for in-depth analysis of scoliosis that limit the ability to see the three-dimensional deformity and expose the patient to considerable doses of radiation, respectively. Our stereophotogrammetric analysis is able to provide accurate, intra-operative measurement of vertebral movement during surgical manuevres. Stereophoto pairs taken at each stage of the operation and robust statistical techniques can be used to determine rotation, translation, goodness of fit, and overall spinal contour before, during, and after the surgical instrumentation. A demonstration of data available from this system is included.

Characterization of bacterial communities in heavy metal contaminated soils.

Heavy metal pollution is a principle source of environmental contamination. We analyzed heavy metal impacted soil microbial communities and found that, in general, although lead adversely affected biomass, metabolic activity, and diversity, autochthonous lead- and cadmium-resistant isolates were found. In several metal-stressed soils, the microbial community consisted of two populations, either resistant or sensitive to lead. Additionally, a lead-resistant isolate was isolated from a control soil with no known previous exposure to lead, suggesting widespread lead resistance. Lead-resistant genera isolated included Pseudomonas, Bacillus, Corynebacterium, and Enterobacter species. Plasmids, ranging from 5 to 260 kb, were not detected through standard purifications from lead-resistant isolates. Positive correlations existed between antibiotic resistance and isolation habitat for lead-resistant strains, microbial metabolic activity and soil type, soluble lead concentration and microbial diversity, and arsenic concentration and total or viable cell concentrations.

Primary talon cusp.

Talon cusps are seen most frequently on maxillary incisors. Only recently have reports of talon cusps on primary teeth appeared. This was a case involving a primary maxillary lateral incisor.

Biodegradation of 2,4,5-trichlorophenoxyacetic acid by a pure culture of Pseudomonas cepacia.

A pure culture of Pseudomonas cepacia, designated AC1100, that can utilize 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) as its sole source of carbon and energy was isolated. An actively growing culture of AC1100 was able to degrade more than 97% of 2,4,5-T, present at 1 mg/ml, within 6 days as determined by chloride release, gas chromatographic, and spectrophotometric analyses. The ability of AC1100 to oxidize a variety of chlorophenols and related compounds is also reported.

Plasmid-assisted molecular breeding: new technique for enhanced biodegradation of persistent toxic chemicals.

The persistence of synthetic herbicides such as 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and its release in massive amounts as a herbicide (Agent Orange) have created toxicological problems in many countries. In nature, 2,4,5-T is slowly degraded by cooxidation and is not utilized as a sole source of carbon and energy. The technique of plasmid-assisted molecular breeding has led to the development of bacterial strains capable of totally degrading 2,4,5-T by using it as their sole source of carbon at high concentrations (greater than 1 mg/ml). Spectrophotometry and gas chromatography reveal various intermediates during growth of the culture with 2,4,5-T.

Plasmid specifying total degradation of 3-chlorobenzoate by a modified ortho pathway.

A plasmid, termed pAC25, specifying biodegradation of 3-chlorobenzoate in a strain of Pseudomonas putida has been characterized. During growth of the plasmid-harboring cells with 3-chlorobenzoate, there was an accumulation of 3-chlorocatechol and beta-chloromuconic acid as intermediates and release of more than 80% of the chlorine in the form of inorganic chloride. The plasmid had a mean molecular mass of 68 x 10(6) daltons and was transmissible to a number of Pseudomonas species such as P. aeruginosa, P. putida strain PpG1, and P. putida strain PRS1. Transfer of pAC25 to various catechol-negative mutants of P. putida strain PRS1 showed that the chromosomally coded pyrocatechase was not complemented by the plasmid-specified pyrocatechase, which appeared to be specific for the chlorinated catechols. In contrast to benzoate, which was metabolized by the ortho pathway through beta-ketoadipate as an intermediate, the plasmid specified ortho cleavage of the chlorocatechols through maleylacetate as an intermediate.

MICRID: a computer-assisted microbial identification system.

An extensive computer-assisted identification system for bacteria and yeasts (117 genera and 1,430 species) was developed, and applications proved very useful in teaching situations.

Computer-assisted identification of anaerobic bacteria.

A computer program was developed to identify anaerobic bacteria by using simultaneous pattern recognition via a Bayesian probabilistic model. The system is intended for use as a rapid, precise, and reproducible aid in the identification of unknown isolates. The program operates on a data base of 28 genera comprising 238 species of anaerobic bacteria that can be separated by the program. Input to the program consists of biochemical and gas chromatographic test results in binary format. The system is flexible and yields outputs of: (i) most probable species, (ii) significant test results conflicting with established data, and (iii) differential tests of significance for missing test results.