Identification of suites of traits that explains drought resistance and phenological patterns of plants in a semi-arid grassland community.

Grassland ecosystems are comprised of plants that occupy a wide array of phenological niches and vary considerably in their ability to resist the stress of seasonal soil-water deficits. Yet, the link between plant drought resistance and phenology remains unclear in perennial grassland ecosystems. To evaluate the role of soil water availability and plant drought tolerance in driving phenology, we measured leaf hydraulic conductance (Ksat), resistance to hydraulic failure (P50), leaf gas exchange, plant and soil water stable isotope ratios (δ18O), and several phenology metrics on ten perennial herbaceous species in mixed-grass prairie. The interaction between P50 and δ18O of xylem water explained 67% of differences in phenology, with lower P50 values associated with later season activity, but only among shallow-rooted species. In addition, stomatal control and high water-use efficiency also contributed to the late flowering and late senescence strategies of plants that had low P50 values and relied upon shallow soil water. Alternatively, plants with deeper roots did not possess drought-tolerant leaves, but had high hydraulic efficiency, contributing to their ability to efficiently move water longer distances while maintaining leaf water potential at relatively high values. The suites of traits that characterize these contrasting strategies provide a mechanistic link between phenology and plant-water relations; thus, these traits could help predict grassland community responses to changes in water availability, both temporally and vertically within the soil profile.

Classification of High-Grade Glioma into Tumor and Nontumor Components Using Support Vector Machine.

BACKGROUND AND PURPOSE: Current imaging assessment of high-grade brain tumors relies on the Response Assessment in Neuro-Oncology criteria, which measure gross volume of enhancing and nonenhancing lesions from conventional MRI sequences. These assessments may fail to reliably distinguish tumor and nontumor. This study aimed to classify enhancing and nonenhancing lesion areas into tumor-versus-nontumor components. MATERIALS AND METHODS: A total of 140 MRI scans obtained from 32 patients with high-grade gliomas and 6 patients with brain metastases were included. Classification of lesion areas was performed using a support vector machine classifier trained on 4 components: enhancing and nonenhancing, tumor and nontumor, based on T1-weighted, FLAIR, and dynamic-contrast-enhancing MRI parameters. Classification results were evaluated by 2-fold cross-validation analysis of the training set and MR spectroscopy. Longitudinal changes of the component volumes were compared with Response Assessment in Neuro-Oncology criteria. RESULTS: Normalized T1-weighted values, FLAIR, plasma volume, volume transfer constant, and bolus-arrival-time parameters differentiated components. High sensitivity and specificity (100%) were obtained within the enhancing and nonenhancing areas. Longitudinal changes in component volumes correlated with the Response Assessment in Neuro-Oncology criteria in 27 patients; 5 patients (16%) demonstrated an increase in tumor component volumes indicating tumor progression. These changes preceded Response Assessment in Neuro-Oncology assessments by several months. Seven patients treated with bevacizumab showed a shift to an infiltrative pattern of progression. CONCLUSIONS: This study proposes an automatic classification method: segmented Response Assessment in Neuro-Oncology criteria based on advanced imaging that reliably differentiates tumor and nontumor components in high-grade gliomas. The segmented Response Assessment in Neuro-Oncology criteria may improve therapy-response assessment and provide earlier indication of progression.

Mechanisms of post-radiation injury: cerebral microinfarction not a significant factor.

Post-radiation leukoencephalopathy is characterized by cognitive impairment and white matter alternations on imaging. Cerebral small vessel disease (SVD) is one of several suggested etiologies. Cerebral microinfarction (CMI) is a recently described marker of SVD. We sought to examine the rate of CMI as a biomarker of ongoing ischemia among patients who underwent brain radiotherapy (RT). 110 patients treated with RT for primary or metastatic brain tumors were enrolled. A total of 685 brain MRI tests performed 1-108 months post-radiation were examined. The annual incidence of CMI was calculated. Only 2 definite CMI were found (2/685, 0.3 %). The calculated annual incidence of CMI was 0.11. This incidence is similar to the normal population, and lower than the reported incidence in patients with intracerebral hemorrhage or cognitive impairment. CMI incidence in patients treated with brain RT is similar to the general population. This finding suggests that post-radiation leukoencephalopathy and cognitive impairment are not due to active SVD solely but rather secondary to other causes such as inflammation, metabolic or direct cell damage.

Early Biomarkers from Conventional and Delayed-Contrast MRI to Predict the Response to Bevacizumab in Recurrent High-Grade Gliomas.

BACKGROUND AND PURPOSE: The interpretation of the radiologic response of bevacizumab-treated patients with recurrent high-grade gliomas represents a unique challenge. Delayed-contrast MR imaging was recently introduced for calculating treatment-response-assessment maps in patients with brain tumors, providing clear separation between active tumor and treatment effects. We studied the application of standard and delayed-contrast MR imaging for assessing and predicting the response to bevacizumab. MATERIALS AND METHODS: Twenty-four patients with recurrent high-grade gliomas were scanned before and during bevacizumab treatment by standard and delayed-contrast MR imaging. The mean change in lesion volumes of responders (overall survival, ≥1 year) and nonresponders (overall survival, <1 year) was studied. The lesion volumes at baseline and the changes in lesion volumes 1 month after treatment initiation, calculated from standard and delayed-contrast MRIs, were studied as possible predictors of outcome. In scans acquired at progression, the average change in lesion volume from previous follow-up in standard and delayed-contrast MRIs was compared. RESULTS: Response and progression patterns were identified from the mean change in lesion volumes, depicted from conventional T1WI, delayed contrast-enhanced MR imaging, and DSC MR imaging. Thresholds for early prediction of response were calculated by using these sequences. For each predictor, sensitivity, specificity, positive predictive values, and negative predictive values were calculated, reaching 85.7%, 87.5%, 75%, and 93.3% for conventional T1WI; 100%, 87.5%, 77.8%, and 100% for delayed-contrast MR imaging; and 75%, 78.6%, 50%, and 91.7% for DSC MR imaging. The benefit of delayed-contrast MR imaging in separating responders and nonresponders was further confirmed by using log-rank tests (conventional T1WI, P = .0022; delayed-contrast MR imaging, P < .0001; DSC MR imaging, P = .0232) and receiver operating characteristic analyses. At progression, the increase in lesion volumes in delayed-contrast MR imaging was 37.5% higher than the increase in conventional T1WI (P < .01); these findings suggest that progression may be depicted more effectively in treatment-response-assessment maps. CONCLUSIONS: The benefit of contrast-enhanced MR imaging for assessing and predicting the response to bevacizumab was demonstrated. The increased sensitivity of the treatment-response-assessment maps reflects their potential contribution to the management of bevacizumab-treated patients with recurrent high-grade glioma.

Impacts of warming and elevated CO2 on a semi-arid grassland are non-additive, shift with precipitation, and reverse over time.

It is unclear how elevated CO2 (eCO2 ) and the corresponding shifts in temperature and precipitation will interact to impact ecosystems over time. During a 7-year experiment in a semi-arid grassland, the response of plant biomass to eCO2 and warming was largely regulated by interannual precipitation, while the response of plant community composition was more sensitive to experiment duration. The combined effects of eCO2 and warming on aboveground plant biomass were less positive in 'wet' growing seasons, but total plant biomass was consistently stimulated by ~ 25% due to unique, supra-additive responses of roots. Independent of precipitation, the combined effects of eCO2 and warming on C3 graminoids became increasingly positive and supra-additive over time, reversing an initial shift toward C4 grasses. Soil resources also responded dynamically and non-additively to eCO2 and warming, shaping the plant responses. Our results suggest grasslands are poised for drastic changes in function and highlight the need for long-term, factorial experiments.

Identifying the ideal profile of French yogurts for different clusters of consumers.

Identifying the sensory properties that affect consumer preferences for food products is an important feature of product development. Different methods, such as external preference mapping or partial least squares regression, are used to establish relationships between sensory data and consumer preferences and to identify sensory attributes that drive consumer preferences, by highlighting optimum products. Plain French yogurts were evaluated by a sensory profiling method performed by 12 trained judges. In parallel, 180 consumers were asked to score their overall liking and complete a cognitive restraint questionnaire. After hierarchical cluster analysis on the liking scores, preference mapping using a quadratic regression model was performed. Five clusters of consumers were identified as a function of different preference patterns. Contrary to our expectations, fat levels were not discriminating. For each cluster, the results of preference mapping enabled the identification of optimum products. A comparison of the 5 sensory profiles revealed numerous differences between key sensory attributes. For example, one consumer cluster had a strong preference for products perceived as very thick, grainy, but with a less flowing texture, less sticky, whey presence and color, in contrast to other clusters. In addition, each segment of consumers was characterized according to the results of the cognitive restraint questionnaire.

The optimal regimen of bevacizumab for recurrent glioblastoma: does dose matter?

The FDA-approved schedule and dose of bevacizumab (BVZ) for recurrent glioblastoma (rGB) (10 mg/kg q 2 weeks) were adopted from systemic cancer protocols. No dose-defining studies have been performed for glioblastoma. We began using BVZ for the treatment of rGB in 2005 at the dose of 5 mg/kg every 2 weeks combined with irinotecan, and later as single agent. Our previous report of 20 patients treated with BVZ 5 mg/kg every 2 weeks showed similar response rates and overall survival (OS) compared to other BVZ treatment protocols, with less adverse effects. In this study we retrospectively reviewed our 7 year experience with BVZ in 162 rGB patients. Treatment outcomes were analyzed from 87 patients who received BVZ at 5 mg/kg and 75 patients at 10 mg/kg. While median age was similar in both groups, the median KPS was significantly higher in the group treated with 10 mg/kg BVZ (85 versus 60). There was no significant difference in OS or progression free survival (PFS) between the groups treated with BVZ 5 versus 10 mg/kg. Overall survival was significantly improved in the subgroup treated with cytotoxic therapy in addition to BVZ 10 mg/kg. There were more adverse events seen with BVZ 10 mg/kg. There is no significant difference in OS for rGB treated with BVZ 5 mg/kg versus 10 mg/kg when given as monotherapy. The smaller dose was slightly less toxic. Addition of cytotoxic therapy resulted in prolongation of OS in a small subgroup of BVZ 10 mg/kg.

Transarterial treatment with Onyx of intracranial dural arteriovenous fistula with cortical drainage in 17 patients.

BACKGROUND AND PURPOSE: Intracranial DAVFs with cortical venous drainage have a high tendency to bleed. Complete closure of these lesions is essential to prevent clinically deleterious events. We describe our experience using Onyx in an arterial approach for treatment of DAVFs in 17 patients. MATERIALS AND METHODS: Between 2006 and 2010, we used Onyx for performing transarterial embolization in 17 patients with intracranial DAVFs and cortical venous drainage. Clinical assessment was performed before and after every treatment at discharge and at follow-up. Fourteen patients underwent follow-up MR imaging and MRA, 8 of them also underwent follow-up diagnostic angiography. RESULTS: Fifteen patients (88%) underwent 1 procedure. Complete obliteration by embolization with Onyx was achieved in 16 patients (94% acute obliteration). The mean amount of Onyx injected was 2.3 mL (range, 0.4-4.8 mL). The sole technical complication was an embolus to a branch of the MCA, which was resolved by intra-arterial tPA injection. A clinical complication of transient trochlear nerve palsy in the same patient due to mass effect of Onyx resolved spontaneously within 3 months. CONCLUSIONS: Intra-arterial embolization of cranial DAVFs with cortical venous drainage by using Onyx results in a high rate of complete obliteration (94%) with low morbidity (6%). Follow-up DSA in 8 patients revealed no evidence of reopening.

Clinical community health: revisiting "the community as patient".

INTRODUCTION: A little over fifty years ago, Edward McGavran, Dean of the University of North Carolina School of Public Health, articulated the concept of treating the community as if it were a patient. Although McGavran was addressing public health practitioners, the concept has applicability in academic medicine and reflects contemporary thought in patient care, research, and education. The goals of this paper are (1) to present a framework through which clinicians can conceptualize the community as an appropriate level of intervention to improve health, to conduct research and to educate students, and (2) to illustrate the framework by presenting information on how programs at Morehouse School of Medicine have used it to organize community-focused initiatives. The concept may be called Clinical Community Health. CLINICAL COMMUNITY HEALTH AND ITS APPLICATIONS AT MOREHOUSE SCHOOL OF MEDICINE: Health problems of communities are more readily understood by clinicians when analyzed in the same way that clinicians analyze the health problems of individual patients: by gathering subjective and objective data, formulating an assessment that is expressed as a problem list, and developing a plan ("SOAP"). The plan is created in consultation with the community, much as a modern physician engages in shared decision-making with a patient rather than issuing "doctor's orders." Similarly, community-based participatory research creates a relationship between the researcher and the community that parallels the relationship between the researcher and the individual research participant in traditional clinical research. When viewed through this lens, the education of students in the community resembles the education of students in the hospital or clinic--both are a type of service-learning. Hence, the community work of faculty is best evaluated and rewarded in a fashion that parallels evaluation of faculty work in the clinic or hospital. This paper reports on our experiences at Morehouse School of Medicine (MSM), a historically black institution in the United States whose mission focuses on primary care and the health of the underserved. We report on our efforts to apply the model in service, research, and education. CONCLUSION: Viewing the community as a patient provides a useful conceptual framework for primary care physicians and other clinicians, since it allows them to recognize that it is not necessary to learn a different conceptual framework to diagnose and treat the community; rather, one can think of the community as a patient and apply a similar approach to that used in the care of individuals.

Increased snow facilitates plant invasion in mixedgrass prairie.

Although global change is known to influence plant invasion, little is known about interactions between altered precipitation and invasion. In the North American mixedgrass prairie, invasive species are often abundant in wet and nitrogen (N)-rich areas, suggesting that predicted changes in precipitation and N deposition could exacerbate invasion. Here, this possibility was tested by seeding six invasive species into experimental plots of mixedgrass prairie treated with a factorial combination of increased snow, summer irrigation, and N addition. Without added snow, seeded invasive species were rarely observed. Snow addition increased average above-ground biomass of Centaurea diffusa from 0.026 to 66 g m(-2), of Gypsophila paniculata from 0.1 to 7.3 g m(-2), and of Linaria dalmatica from 5 to 101 g m(-2). Given added snow, summer irrigation increased the density of G. paniculata, and N addition increased the density and biomass of L. dalmatica. Plant density responses mirrored those of plant biomass, indicating that increases in biomass resulted, in part, from increases in recruitment. In contrast to seeded invasive species, resident species did not respond to snow addition. These results suggest that increases in snowfall or variability of snowfall may exacerbate forb invasion in the mixedgrass prairie.

The value of ventriculo-peritoneal shunting in patients with glioblastoma multiforme and ventriculomegaly.

BACKGROUND: Patients with an advanced-stage glioblastoma multiforme (GBM) often show general motor, gait, and cognitive deterioration. Some have radiological evidence of ventriculomegaly, but the relevance of this to their symptoms may be unclear. Distinction between tumour patients who have dilated fluid spaces as a consequence of tissue loss from surgery or treatment, and those who have a symptomatic hydrocephalic process, one who may gain benefit from insertion of a ventriculo-peritoneal shunt, is an important clinical challenge. METHODS: From a series of 530 GBM patients treated by a single surgeon (ZR), we retrospectively reviewed 16 patients with advanced-stage GBM who had presented with non-obstructive ventriculomegaly and clinical deterioration not explained by progressive disease. Each had been treated by insertion of a ventriculo- peritoneal shunt (VPS). Assessments included clinical features, Karnofsky Performance Scale, motor and cognitive findings, complications and survival. FINDINGS: Ten patients benefited from insertion of the shunt, with moderate to significant cognitive improvement. Of seven patients who presented with motor symptoms, such as gait instability, general weakness, and slowness, four patients showed significant motor improvement in addition to major cognitive improvement. Early infectious complication occurred in five patients; a late shunt infection in one; one patient had symptoms related to overdrainage; and in another a mechanical shunt malfunction occurred. Three patients died from shunt-related complications. CONCLUSIONS: Insertion of a ventriculo-peritoneal shunt can improve cognitive and motor function in a small subset of patients with advanced-stage glioblastoma multiforme and ventriculomegaly. Infection is a major risk in this patient population.

Early pathologic findings and long-term improvement in anti-Ma2-associated encephalitis.

A 67-year-old man sequentially developed anti-Ma2-associated paraneoplastic encephalitis (PNE) and contralateral herpes simplex encephalitis (HSE). Brain biopsy 1 month before HSE revealed extensive infiltrates of T cells, B cells, and plasma cells. Most T cells expressed the cytotoxic granule-associated protein TIA-1 and the membranolytic protein granzyme-B. Although recovery was thought to be unlikely, treatment of the PNE with corticosteroids and resection of the associated lung cancer resulted in dramatic improvement for 21 months.

Efficacy of local dipyridamole therapy in a porcine model of arteriovenous graft stenosis.

Perivascular delivery of antiproliferative drugs has been proposed as an approach to prevent neointimal hyperplasia associated with hemodialysis polytetrafluoroethylene (PTFE) grafts. We examined this approach to deliver dipyridamole in a porcine graft model. PTFE grafts were implanted between the carotid artery and external jugular vein bilaterally in pigs. During the surgery or 1 week post-graft placement, dipyridamole (0.26-52 mg) alone or incorporated in microspheres was mixed with an injectable polymeric gel and applied to the graft-arterial and graft-venous anastomoses on one side, whereas the contralateral control graft received no treatment. Three or four weeks after operation, the grafts and adjacent vessels were explanted en bloc and cross-sections of the anastomoses were examined histologically. The degree of neointimal hyperplasia was quantified by planimetry. In separate experiments, dipyridamole was extracted from the explanted tissues and assayed by spectrofluorometry. The normalized median hyperplasia areas of the treated and control graft-venous anastomoses were 0.45 (25th-75th percentile, 0.30-0.86) and 0.24 (0.21-0.30), respectively (N=7; P=0.08). The median hyperplasia areas of the treated and control graft-arterial anastomoses were 0.12 (0.07-0.39) and 0.11 (0.09-0.13), respectively (N=7; P=0.31). The dipyridamole levels in the vascular walls around the anastomoses were at or above the in vitro inhibitory concentrations for approximately 3 weeks. These results suggest that the local perivascular sustained delivery of dipyridamole, even at high dosages, was ineffective in inhibiting neointimal hyperplasia associated with PTFE grafts in a porcine model.

Capecitabine-induced multifocal leukoencephalopathy: a report of five cases.

Capecitabine is used to treat advanced breast and gastrointestinal malignancies. A single case of encephalopathy and three cases of peripheral neuropathy are the only neurotoxicities reported. The authors report five additional cases of capecitabine-induced multifocal leukoencephalopathy.

Chromogenic in situ hybridization accurately identifies EGFR amplification in small cell glioblastoma multiforme, a common subtype of primary GBM.

Primary glioblastoma multiforme (GBM) commonly overexpresses the epidermal growth factor receptor (EGFR) gene and its ligand-independent mutant, EGFRvIII. Amplification of the EGFR gene has been implicated in the pathogenesis of primary GBM, in particular the small cell phenotype, and this finding may contribute to its aggressive clinical behavior. Anti-EGFR clinical trials for GBM are being conducted, and it would be useful to identify a rapid technique to determine whether EGFR expression and the small cell phenotype are associated with a response to therapy. In the present study we examined 56 cases of GBM using chromogenic in situ hybridization (CISH). CISH analysis and morphology identified 22 small cell (SCGBM) and 22 non-small cell glioblastoma (NSCGBM), and 12 cases of a mixed phenotype. Fourteen cases of SCGBM (14/22) showed EGFR amplification, while only 5 NSCGBM (5/22) cases showed amplification. We have therefore used CISH as an efficient, economic and reliable means for routinely assessing EGFR amplification in GBM, including the small cell variant.

Market competition and patient-oriented research: the results of a national survey of medical school faculty.

PURPOSE: To understand the effect of market competition on patient-oriented research at U.S. medical schools and teaching hospitals. METHOD: From a multi-stage stratified, random sample, the authors surveyed 3,804 research faculty at 117 U.S. medical schools. The questionnaire assessed five variables, the type of research conducted by the respondent, changes in patient-oriented and non-clinical research in the preceding three years, amount of time spent on patient care, market stage of the respondent's institution, and research productivity. RESULTS: Of the 2,336 faculty who responded (62%), 84% of those conducting patient-oriented research and 80% of those engaged in non-clinical research reported conducting the same amount of research or more in 1996-1997 than in the preceding three years. However, both patient-oriented and non-clinical researchers in the most competitive health care markets and those with high levels of patient care duties were most likely to report decreases in the amounts of such research conducted in the previous three years. Further, researchers reporting such decreases had been as productive in recent years and over their careers as had those who did not report a decrease. CONCLUSIONS: This study provides additional evidence of the negative relationships that exist between high levels of market competition and patient care services on the patient-oriented and non-clinical research missions of teaching hospitals.

A comparison of videotape and audiotape assessment of patient-centredness in family physicians' consultations.

The aim of this study was to compare videotape and audiotape assessments of doctors' patient-centred behaviour in primary care consultations. The patient-centredness scale of Henbest and Stewart was used to measure the quality of 856 doctor-patient interactions in 258 consultations performed by 47 primary care physicians recorded on videotape. Assessments were performed once using only the sound track and a second time using both the sound and video-tracks. On a nominal quality scale of 0-3, the average score for all consultations was 1.94 (S.D. 0.63) by audio assessment, and 1.94 (S.D. 0.59) by video assessment (P<0.8). There was excellent agreement between audio and video scores over a wide range of scores. Little information (<5%) was lost when using audiotape compared to videotape. It was technically easier to assess the video recordings. Audio recording is equivalent to video recording for the assessment of patient-centredness using the scale of Henbest and Stewart in primary care consultations.