Knowledge-based isocenter selection in radiosurgery planning.

PURPOSE: We present a new method for knowledge-based isocenter selection for treatment planning in radiosurgery. Our objective is to develop a prediction model that can learn from past manually designed treatment plans. We leverage recent advances in deep learning to predict isocenter locations in treatment plans in order to provide a decision support tool. METHODS: The proposed method adapts a geometric approach using orthogonal moment expansions as a feature vector for describing the shape of the tumor. Our approach accounts primarily for tumor shape and OAR proximity, the two factors that are known to greatly affect the isocenter placement. We solve the prediction problem by training a residual neural network with skip connections on the formed shape descriptors. Our network was trained on 533 patient cases and was validated on a set of out-of-sample cases. RESULTS: Our method generates heatmap predictions for isocenter locations that are in most cases comparable to the experienced human planners, which shows that the method can be used in treatment planning to guide the users for determining the isocenters. CONCLUSIONS: Our numerical experiments indicate a positive predictive value on an independent validation set when compared against a test dataset that was not seen by the model during training.

Simultaneous optimization of isocenter locations and sector duration in radiosurgery.

Stereotactic radiosurgery is an effective technique to treat brain tumors for which several inverse planning methods may be appropriate. We propose an integer programming model to simultaneous sector duration and isocenter optimization (SDIO) problem for Leksell Gamma Knife® IconTM (Elekta, Stockholm, Sweden) to tractably incorporate treatment time. We devise a Benders decomposition scheme to solve the SDIO problem to optimality. The performances of our approaches are assessed using anonymized data from eight previously treated cases, and obtained treatment plans are compared against each other and against the clinical plans. The plans generated by our SDIO model all meet or exceed clinical guidelines while demonstrating high conformity.

Modeling and comparison of alternative approaches for sector duration optimization in a dedicated radiosurgery system.

Stereotactic radiosurgery (SRS) is an effective technique to treat brain metastasis for which several inverse planning methods may be appropriate. We compare three different optimization models for segment duration optimization in SRS using Leksell Gamma Knife® IconTM (Elekta, Stockholm, Sweden). We investigate (1) a linear programming approach, (2) a piecewise quadratic penalty approach, and (3) an unconstrained convex moment-based penalty approach. We examine the performances of these approaches using anonymized data from 14 previously treated cases. In addition, we investigate the important modeling question of selecting weights for the objective functions where we use a simulated annealing algorithm to determine these weights for each model. The inverse plans obtained via optimization models are compared against each other and against the clinical plans. The three inverse planning models can all yield optimal treatment plans in a reasonable amount of time and the treatment plans obtained by these models meet or exceed clinical guidelines while displaying high conformity.

Is the Latin American and Caribbean Food Security Scale an Appropriate Instrument for Mexican Urban Older Adults?

BACKGROUND: Older adults in Mexico are a growing share of the population and are a largely vulnerable group with increased risk of food insecurity and potential detrimental health effects stemming from it. OBJECTIVES: This study assesses the face validity of the Latin American and Caribbean Food Security Scale (ELCSA) among Mexican urban older adults of low socioeconomic status. DESIGN: Qualitative study based on 4 focus groups. SETTING: The focus groups were conducted in community organizations for the elderly in an area of Mexico City with a high proportion of poverty. PARTICIPANTS: The focus groups included a total of 36 older adults aged 65 and over who consented to participate. MEASUREMENTS: Two initial focus groups were conducted to assess how older adults understood the food security construct and each of the ELCSA items. Based on these findings, ELCSA was modified and retested for face validity through two additional focus groups. RESULTS: The initial focus groups suggested that several of the scale items were not well understood, leading to editorial modifications of the scale. The final focus groups indicated that the modified version of the scale improved substantially ELCSA's face validity in this sample. CONCLUSIONS: The modified ELCSA led to a greater understanding of most scale items. Further qualitative research is needed to improve food insecurity measurements among older adults in Latin America.

Memantine protects cholinergic and glutamatergic septal neurons from Aß1-40-induced toxicity.

The medial septal region (medial septum and diagonal band of Broca, MS/DB) controls hippocampal excitability and synaptic plasticity. MS/DB cholinergic neurons degenerate early in Alzheimer's disease (AD). The presence of MS/DB glutamatergic neurons that project to the hippocampus and are vulnerable to Aß suggests that excitotoxicity plays a role in AD septal degeneration and hippocampal dysfunction. To demonstrate the presence of excitotoxicity in Aß-induced septal damage, we compared rats injected with Aß1-40 into the MS/DB with animals treated with memantine prior, during and after Aß1-40 injections. Controls were injected with phosphate buffered saline (PBS). MS/DB cholinergic, glutamatergic and GABAergic neurons were immunochemically identified. The number of MS/DB neurons was estimated using stereology. Our results show that memantine blocks Aß1-40-induced septal damage and suggest that excitotoxicity plays a role in basal forebrain neurodegeneration.

SU-D-211-03: An Automated Inverse Planning Optimization Approach for Single- Fraction and Fractionated Radiosurgery Using Gamma Knife Perfexion.

PURPOSE: The purpose of this work is to develop an automated inverse planning approach to generate singe-fraction and fractionated stereotactic radiosurgery (SRS) treatment plans for Gamma Knife Perfexion. METHODS: Our automated approach consists of two steps: 1) a grassfire-based algorithm to carefully determine the isocentre locations; 2) a penalty-based optimization to find the optimal shot shapes and their intensities to minimize the deviation of the delivered dose from the objective dose in all structures. For single-fraction SRS, a margin-less approach was taken: conformity of dose to the gross tumor volume (GTV) with a steep dose fall-off was prioritized. For fractionated radiosurgery, dose homogeneity was given a higher priority since planning target volumes (PTV) were applied to account for daily setup variation, and these PTVs could overlap with organs-at-risk (OARs). The two-step approach was tested on seven clinical cases with PTV sizes of 0.5cm̂3-56.5cm̂3. In the tested cases, the PTV had 0%-38% overlap with OARs. RESULTS: For single-fraction SRS, the dose to 1mm̂3 brainstem was on average 0.24Gy (range: -2.4Gy to +2.0Gy) lower compared to manually-generated plans. Beam-on time varied with the number of isocentres, but on average was 33min longer than manually- generated plans. The optimization algorithm took 215min on average, while isocentre selection performed in <10s.For fractionated SRS, the average PTV coverage was V95=94.9% (range: 92.7%-97.6%) and the mean dose to 1 mm̂3 brainstem was 87.8% of the prescription dose (range: 35.4%- 108.8%). The mean beam-on time per fraction per dose-per-fraction was 4.8min/Gy (range: 0.9min/Gy-10.3min/Gy). We observed a tradeoff between conformity and OARs-sparing in both plans, and added sensitivity to isocentre locations in fractionated plans. In all the cases, GTV received the full prescription dose. CONCLUSIONS: The results indicated that automated inverse planning yields improved conformity and OAR-sparing for single- fraction SRS and is capable of generating homogeneous fractionated SRS. This work is partially funded by Elekta Instrument, AB, Stockholm, Sweden.

Apparent diffusion coefficient reveals gray and white matter disease, and T2 mapping detects white matter disease in the brain in feline alpha-mannosidosis.

BACKGROUND AND PURPOSE: Methods to locate and identify brain pathology are critical for monitoring disease progression and for evaluating the efficacy of therapeutic intervention. The purpose of this study was to detect cell swelling, abnormal myelin, and astrogliosis in the feline model of the lysosomal storage disease alpha-mannosidosis (AMD) by using diffusion and T2 mapping. MATERIALS AND METHODS: Average apparent diffusion coefficient (ADC(av)) and T2 were measured by imaging the brains of five 16-week-old cats with feline AMD on a 4.7T magnet. ADC(av) and T2 data from affected cats were compared with data from age-matched normal cats. Brains were collected from both affected and normal cats following imaging, and histology was compared with quantitative imaging data. RESULTS: Gray matter from AMD cats demonstrated a 13%-15% decrease in ADC(av) compared with that in normal cats. White matter from AMD cats exhibited an 11%-16% decrease in ADC(av) and a 5%-12% increase in T2 values compared with those in normal control cats. Histologic evidence of neuronal and glial swelling, abnormal myelin, and astrogliosis was consistent with changes in ADC(av) and T2. CONCLUSION: ADC(av) and T2 data can be used to quantify differences in the gray and white matter in the feline AMD brain and may serve as surrogate markers of neuronal swelling, abnormal myelin, and astrogliosis associated with this disease. These studies may be helpful in assessing the efficacy of experimental therapies for central nervous system disease associated with lysosomal storage diseases.

Functional magnetic resonance imaging of eye dominance at 4 tesla.

We studied eye dominance in visual cortex and lateral geniculate nucleus (LGN) using functional magnetic resonance imaging (fMRI) at a very high magnetic field (4 tesla). Eight normal volunteers were studied with fMRI at 4 tesla during alternating monocular visual stimulation. The acquisition was repeated twice in 4 subjects to confirm reproducibility. In addition, magnetic resonance signal intensities during three conditions (right eye stimulation, left eye stimulation, and control condition) were compared to determine whether the observed area was truly or relatively monocular in 2 subjects. In both the individual and group analyses, the anterior striate cortex was consistently activated by the contralateral eye more than the ipsilateral eye. Additionally, we found evidence that there were areas in the bilateral LGN which were more active during the stimulation of the contralateral eye than during the stimulation of the ipsilateral eye. The activated areas were reproducible, and the mean ratio of the overlapping area was 0.71 for the repeated scans. The additional experiment revealed that the area in the anterior visual cortex could be divided into two parts, one truly monocular and the other relatively monocular. Our finding confirmed previous fMRI results at 1.5 tesla showing that eye dominance was observed in the contralateral anterior visual cortex. However, the eye dominance in the visual cortex was found not only in the most anterior area corresponding to the monocular temporal crescent but also in the more posterior area, presumably showing the greater sensitivity of the temporal visual field (nasal retina) as compared with the nasal visual field (temporal retina) in the peripheral visual field (peripheral retina). In addition, it is suggested that the nasotemporal asymmetry of the retina and the visual fields is represented in the LGN as well as in the visual cortex.

Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion.

PURPOSE: Patients with one of the 22q11.2 deletion syndromes provide a unique opportunity to research the interface between genetics and brain-behavior relationships. This study investigates the neuropsychological characteristics and behavioral phenotype of children with this deletion syndrome. METHODS: We report updated findings from descriptive and nonparametric analyses of neuropsychological data from 80 children with the 22q11.2 deletion. RESULTS: The subjects showed higher verbal than nonverbal IQ scores, assets in verbal memory, and deficits in the areas of attention, story memory, visuospatial memory, arithmetic performance relative to other areas of achievement, and psychosocial functioning. CONCLUSION: Children with 22q11.2 deletion syndromes exhibit a behavioral phenotype reflective of nonverbal learning disabilities, concomitant language deficits, and social-emotional concerns.

Communication issues in 22q11.2 deletion syndrome: children at risk.

PURPOSE: The purpose of this investigation is to describe the communication profile of children with the 22q11.2 deletion syndrome from infancy through school age and to examine the influence of other medical aspects, such as palate anomalies, learning disorders, and cardiac defects of the syndrome to communication. METHODS: Seventy-nine children were examined using standardized tests of speech and language and perceptual measures of resonance and voice. RESULTS: Results show significant delay in emergence of speech and language milestones with delay/disorder in speech-language processes persisting into the school aged years, including those children diagnosed with nonverbal learning disabilities. Persistent articulation and resonance disorders were also present, presumed to be related in part to palatal anomalies. No correlation was found between cardiac status, learning disorders, palate anomalies and communication disorders. CONCLUSION: The need for early identification and management of communication skills is crucial in the care of children with the 22q11.2 deletion.

Visual activation in functional magnetic resonance imaging at very high field (4 Tesla).

OBJECTIVES: Functional magnetic resonance imaging (fMRI) at very high field strengths provides functional brain mapping with the enhanced signal to noise ratio and the larger blood oxygenation level-dependent (BOLD) effect. We report activated areas in the standard space detected by fMRI at 4 Tesla (T) during simple visual stimulation. MATERIALS AND METHODS: Twelve healthy young subjects were scanned using a 4 T scanner during binocular flashing visual stimulation. Functional images were realigned to the first scan and then spatially normalized. Individual and group data analyses were performed to identify areas of visual activation. RESULTS: Activation of the bilateral primary visual cortex (V1/V2) was observed along the entire calcarine fissure in all subjects. The activated area extended to the extrastriate cortex in all subjects. Activation of the bilateral lateral geniculate nucleus (LGN) was detected in all subjects. The group data showed activation of the bilateral primary visual cortex and the bilateral lateral geniculate nucleus. CONCLUSIONS: Robust activation of the vision-related areas was successfully obtained in all subjects using a 4 T magnetic resonance scanner. These results suggest that fMRI at very high field strengths may be effective in showing visual system physiology, and that it can be a promising method to assess visual function of human subjects.

[Prevalence of latent toxoplasma infection in HIV infection patients]. / Prevalencia de infección latente frente a toxoplasma en pacientes con infección VIH.

BACKGROUND: To know the prevalence of Toxoplasma gondii latent infection in HIV-1 infected patients and to compare it with the prevalence in a group of parenteral drug users, non-infected by HIV. METHODS: We study 255 HIV-1 patients revised in our hospital in the last 6 years. The control group were 116 drug addicts non-infected by HIV followed in an educational program of deshabituation. We tested IgG anti-toxoplasma by enzymatic inmunoessay (MEIA). An IgG plasma value of 6UI/ML or more was an indicative of toxoplasma previous infection. We used Chi Square and Yatchts correction tests for the statistical analysis, settling down a significance point of 95%. RESULTS: We founded 36.7% positive IgG anti-toxoplasma in the group on HIV-1 infected patients, non drugs addicts, against 30.9% in the group of HIV-1 drug addicts patients. (OR 0.77; 0.35 < OR < 1.66). The control group showed a Toxoplasma seroprevalence of 26.7%, without statistically significant against the drug addicts HIV group (OR = 1.55; 0.93 < OREGON < 2.59). CONCLUSIONS: The seroprevalence of Toxoplasma gondii latent infection in our study was similar to the european results. We didn't found a higher prevalence in HIV-1 patients than in patients non infected by HIV-1.

Achieving excellence in thrombolytic therapy.

Hospitals today are challenged to provide high-quality, high-technology, cost-effective care while maintaining a humanistic approach toward patients and their families. Thrombolytic therapy for patients with acute myocardial infarction (AMI) can present challenges to emergency department and critical care nursing staff members. The areas of concomitant medications, screening checklists, associated laboratory studies, and overall time to treatment presented opportunities for improvement at a Florida hospital. The clinical process and the existing quality improvement activities were reviewed by a multidisciplinary continuous quality improvement (CQI) team. The outcomes of the CQI process were extremely favorable; 100% compliance was achieved in all aspects of care for patients with AMI.

The effects of opioid blockade and GnRH administration upon luteinizing hormone secretion in patients with anorexia nervosa during the stages of weight loss and weight recovery.

OBJECTIVE: We examined the functional status of the hypothalamic-opioid system involved in LH secretion and the pituitary LH sensitivity and reserve in patients with anorexia nervosa were studied during body weight loss and weight recovery. We measured the temporal relationship between weight recovery, expression of hypothalamic-opioid activity and pituitary GnRH responsiveness, and resumption of ovulatory cycles. DESIGN: Five patients with anorexia nervosa were prospectively studied during weight loss and amenorrhoea, subsequently when they reached their ideal body weight but still remained amenorrhoeic and thereafter every 6 months until resumption of ovulatory cycles; one patient was studied only during weight loss, two during ideal body weight and amenorrhoea and one during ideal body weight and ovulatory cycles. Blood was sampled every 10 minutes over a 16-hour period on two alternate days. On study day 1 (control day), patients received two sets of saline infusion every 6 hours and one saline bolus at the beginning of the seventh hour; on study day 3 (experimental day), they received a saline infusion during the first 6 hours, an intravenous bolus of naloxone (20 mg) at the beginning of the seventh hour and then a continuous naloxone infusion (1.6 mg per hour) during the ensuing 6 hours. Pituitary LH sensitivity and reserve were assessed on both study days by the subsequent administration of 5 and 95 micrograms of GnRH 4 hours before the completion of each sampling period. Patients in ideal body weight and ovulatory cycles as well as five normal menstruating women included in the study for comparative purposes, were studied during the midluteal phase of a cycle. MEASUREMENTS: LH, oestradiol and progesterone were determined by radioimmunoassay. Areas under the LH curve were calculated by the trapezoid method; LH pulse detection was carried out by the program Cluster. RESULTS: Naloxone administration to patients with anorexia nervosa in the weight loss phase, did not significantly modify their serum LH levels nor the characteristics of its pulsatile secretion. Administration of the opioid blocker induced a significant increase in serum LH concentrations only in those patients in ideal body weight and amenorrhoea who resumed ovulatory cycles within the 6 months following the last study as well as in patients with an ideal body weight and ovulatory cycles and in normal controls. All patients and subjects who responded to naloxone administration exhibited significant increases in the area under the LH curve, mean LH pulse amplitude and peak area. Patients in ideal body weight and amenorrhoea who did not resume ovulatory cycles within the 6 months following the study days, did not respond to naloxone administration. There were no significant correlations between the magnitude of LH response to naloxone administration and the baseline levels of serum oestradiol and progesterone. All patients exhibited significant pituitary LH responses to both GnRH doses, regardless of the stage of the disease; however, the pituitary responsiveness shown by patients in ideal body weight was significantly higher than that presented by patients in weight loss. There were no significant differences between the responses to GnRH exhibited by patients in ideal body weight and amenorrhoea who responded to naloxone administration and those shown by patients in the same clinical condition but who were insensitive to opioid blockade. CONCLUSIONS: The re-establishment of hypothalamic-opioid inhibitory activity involved in LH secretion in patients with anorexia nervosa during the phase of weight gain predicts imminent restoration of ovulatory cycles. Pituitary LH response to exogenous GnRH during weight recovery does not accurately predict the outcome of the disease regarding reinitiation of menstrual cycles; however, it might be an indicator that the normal function of the hypothalamic-pituitary axis is being restored.

Effects of parabrachial opioid antagonism on stimulation-induced feeding.

The pontine parabrachial nucleus (PBN) contains gustatory relay neurons and a high concentration of opioid receptors. To investigate the involvement of PBN opioid activity in feeding behavior, antagonists were infused into the PBN bilaterally and effects on stimulation-induced feeding were determined. Naloxone, a mu-preferring antagonist, increased the lateral hypothalamic stimulation threshold for eliciting feeding behavior while nor-binaltorphimine, a kappa-selective antagonist, did not. Neither antagonist increased threshold when infused into dorsal pontine sites outside of the PBN or the fourth ventricle. In as much as PBN contains mu and kappa but no detectable delta receptors, the present results suggest that mu opioid activity within the PBN is involved in the mediation of feeding behavior.

Age differences in within-session habituation of exploratory behavior: effects of stimulus complexity.

The effects of age on the habituation of exploratory behavior of 8-month- and 28-month-old male C57BL/NNia mice were examined under three different stimulus complexity conditions. Increases in the degree of stimulus complexity resulted in an attenuation of between-session habituation and an initial disruption of within-session habituation by 8-month-old mice. Although increases in stimulus complexity also resulted in an increase in the overall level of exploration by aged mice, stimulus complexity was not found to have a systematic effect on between- or within-session habituation by aged mice. No between-session habituation was observed in aged mice under any of the stimulus complexity conditions. Further, aged mice exhibited significant within-session increases, rather than decreases, in exploration under each stimulus complexity condition. This disruption of within-session habituation in aged mice was found to persist over four daily test sessions. In view of the specific patterns of exploration by aged mice, the disruption of within-session habituation was attributed to age-related differences in reactivity to the arousal-inducing properties of novel stimuli.

Analgesic effects of ethylketocyclazocine and morphine in rat and toad.

We have previously found rat and toad (Bufo marinus) brain to contain inverse ratios of benzomorphan-preferring (kappa/sigma) and morphine-preferring (mu) opioid receptor types. The aim of the present study was to compare in vivo pharmacologic activity of a benzomorphan, ethylketocyclazocine (EKC) and morphine sulfate (MS) in rat and toad. Footshock intensity thresholds for eliciting locomotion were determined and dose-response curves for EKC and MS analgesia were obtained. Drugs were injected subcutaneously. In rats (high mu, low kappa in brain), both compounds produced analgesia and displayed similar sensitivity to naloxone antagonism. The analgesic effects of EKC and MS may, therefore, be mediated by a common receptor type (mu) in this pain test in rats. In toads (high kappa, low mu in brain), MS produced naloxone-reversible analgesia at doses 20-fold higher than were effective in rats. Toads did not display EKC analgesia at doses below those producing motor impairment. Moreover, 50-fold higher doses were required to produce such impairment in toads. Thirty minutes following subcutaneous injection of 3H-EKC, similar concentrations were found in rat and toad brain. Uptake into brain is probably not a factor in the behavioral resistance of toads to EKC.

Evaluation of Urea-motility-indole medium for recognition and differentiation of Salmonella and Shigella species in stool cultures.

A semisolid urea-motility-indole medium designed for detection in Enterobacteriaceae of urease activity, motility, and indole production in one tube was prepared and evaluated. The formulation of the medium was similar to that of Christensen urea agar, but the agar concentration was 0.2%, and 1% tryptone was added. Results with 687 strains of Enterobacteriaceae were the same as those obtained with standard test media (98% overall agreement). The urea-motility-indole medium was also used in combination with Kligler iron agar for the recognition and differentiation of Salmonella and Shigella species from colonies picked from plating media in fecal cultures. This combination was compared with the combination of Kligler iron agar and lysine iron agar with 507 strains of non-lactose-fermenting Enterobacteriaceae. Although both combinations enabled the presumptive recognition and differentiation of Salmonella and Shigella species, an analysis of data indicated that the combination of Kligler iron agar and urea-motility-indole medium performed better than the combination of Kligler iron agar and lysine iron agar in detecting Salmonella and Shigella species.