Growing demands on water supply worldwide have resulted in aquifer overdraft in many regions, especially in alluvial basins under intensive irrigation. This further leads to serious deterioration of groundwater quality. Managed aquifer recharge (MAR) has been shown to mitigate groundwater overdraft, but whether MAR can actually stabilize or reverse the ongoing declines in regional groundwater quality caused by non-point sources has not been demonstrated. This study was intended to address the question by investigating impacts of different MAR strategies on regional groundwater quality. A geostatistical model was first used to characterize a heterogeneous alluvial aquifer system in a portion of the Tulare Lake Basin. Three-dimensional numerical models were then employed to simulate groundwater flow and mass transport. Next, MAR strategies were applied in locations with different geological conditions or joint with different irrigation activities, and their performances were evaluated. Results demonstrate the potential of significant, long-term benefits for regional groundwater quality by applying strategic, high-intensity recharge operations on geologically favorable subregions. Siting MAR above the incised valley fill (IVF) deposit, a near-surface paleochannel containing unusually coarse, high-conductivity hydrofacies, leads to more extensive improvement in the groundwater quality in terms of salinity due to significant vertical flow and lateral outward flow from the IVF. Overall, decades would be required to alleviate groundwater quality concerns in the studied 189 km2 region. The simulations indicate that the deep concentrations remain below the secondary maximum contaminant level as the solute mass migrates downward with the prominent contribution from the attenuation via dispersion and matrix diffusion.

Background

Internal medicine fellowship programs have an incentive to select fellows who will ultimately publish. Whether an applicant's publication record predicts long term publishing remains unknown.

Methods

Using records of fellowship bound internal medicine residents, we analyzed whether publications at time of fellowship application predict publications more than 3 years (2 years into fellowship) and up to 7 years after fellowship match. We calculate the sensitivity, specificity, positive and negative predictive values and likelihood ratios for every cutoff number of application publications, and plot a receiver operator characteristic curve of this test.

Results

Of 307 fellowship bound residents, 126 (41%) published at least one article 3 to 7 years after matching, and 181 (59%) of residents do not publish in this time period. The area under the receiver operator characteristic curve is 0.59. No cutoff value for application publications possessed adequate test characteristics.

Conclusion

The number of publications an applicant has at time of fellowship application is a poor predictor of who publishes in the long term. These findings do not validate the practice of using application publications as a tool for selecting fellows.

This is the first systematic study of Chinese children's brain development. Using optimized voxel-based morphometry, we investigated age-related changes in gray and white matter in Chinese children and adolescents aged 7 to 23 years. Results showed mostly linear reductions, but also some linear increases, in gray matter in many regions of the brain. Gray matter changes were more evident in the parietal and temporal regions than in the frontal and occipital regions. White matter showed significant linear increases in internal capsule, arcuate fasciculus, superior and inferior longitudinal fasciculus, and cingulate fasciculus.

These studies focused on a new radiolabeling technique with copper ((64)Cu) and zirconium ((89)Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of (64)Cu-CD45 and (89)Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of (64)Cu-TETA-CD45 increased from 0 (92%) to 160 µCi/mL (76%, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of (64)Cu-TETA-CD45 >20 µCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 µCi/mL (p<0.05). For (89)Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of (89)Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 µCi/mL compared to 0-40 µCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of (89)Zr-Df-CD45 labeling efficiency was observed when compared to (64)Cu-TETA-CD45. Similar to (64)Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 µCi/mL (p<0.05) (growth, colony formation). Taken together, 20 µCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×10(6) hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of (89)Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that (89)Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high.

Alzheimer's disease (AD) is one of the most serious progressive neurodegenerative diseases among the elderly, therefore the identification of conversion to AD at the earlier stage has become a crucial issue. In this study, we applied multimodal support vector machine to identify the conversion from normal elderly cognition to mild cognitive impairment (MCI) or AD based on magnetic resonance imaging and positron emission tomography data. The participants included two independent cohorts (Training set: 121 AD patients and 120 normal controls (NC); Testing set: 20 NC converters and 20 NC non-converters) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The multimodal results showed that the accuracy, sensitivity, and specificity of the classification between NC converters and NC non-converters were 67.5% , 73.33% , and 64% , respectively. Furthermore, the classification results with feature selection increased to 70% accuracy, 75% sensitivity, and 66.67% specificity. The classification results using multimodal data are markedly superior to that using a single modality when we identified the conversion from NC to MCI or AD. The model built in this study of identifying the risk of normal elderly converting to MCI or AD will be helpful in clinical diagnosis and pathological research.

This study examined cerebral asymmetry, especially in the hierarchical visual system, when reading Chinese characters. Twelve right-handed Chinese children (mean age = 11.6 years) were scanned while performing semantic and phonological tasks. Strong leftward asymmetry was found in the left inferior frontal cortex (BA44/45/47), the parietal lobule (BA40), and the cingulate cortex (BA24/32). In the visual system, we found significant left-hemispheric dominance in the fusiform cortex (BA19/37), but no asymmetry was found in the primary visual cortex (BA17/18). The differential results for the primary visual cortex versus high-order visual cortex (i.e., the fusiform cortex) are discussed in terms of the contribution of the logographic nature of Chinese characters to the asymmetry pattern in the hierarchical visual system.

Alzheimer's disease (AD) is the most common type of dementia in the elderly with no effective treatment currently. Recent studies of noninvasive neuroimaging, resting-state functional magnetic resonance imaging (rs-fMRI) with graph theoretical analysis have shown that patients with AD and mild cognitive impairment (MCI) exhibit disrupted topological organization in large-scale brain networks. In previous work, it is a common practice to threshold such networks. However, it is not only difficult to make a principled choice of threshold values, but also worse is the discard of potential important information. To address this issue, we propose a threshold-free feature by integrating a prior persistent homology-based topological feature (the zeroth Betti number) and a newly defined connected component aggregation cost feature to model brain networks over all possible scales. We show that the induced topological feature (Integrated Persistent Feature) follows a monotonically decreasing convergence function and further propose to use its slope as a concise and persistent brain network topological measure. We apply this measure to study rs-fMRI data from the Alzheimer's Disease Neuroimaging Initiative and compare our approach with five other widely used graph measures across five parcellation schemes ranging from 90 to 1,024 region-of-interests. The experimental results demonstrate that the proposed network measure shows more statistical power and stronger robustness in group difference studies in that the absolute values of the proposed measure of AD are lower than MCI and much lower than normal controls, providing empirical evidence for decreased functional integration in AD dementia and MCI.

The catechol-O-methyltransferase (COMT) Val¹⁵⁸Met polymorphism has been associated with working memory (WM) in many studies, but the results have not been consistent. One plausible explanation is sex-specific effects of this polymorphism as reported in several studies. The current study aimed to explore the sex-specific effects of the COMT Val¹⁵⁸Met polymorphism on WM-related brain function in an elderly sample. We found that Val homozygotes outperformed Met allele carriers on the backward digit span subtest for both males and females. The triangular part of the left inferior frontal gyrus and the left inferior temporal gyrus exhibited higher activation in Met allele carriers compared with Val homozygotes during the n-back task, while the background functional connectivity (bFC) between the left angular gyrus (ANG) and the right ANG was enhanced in Val homozygotes as compared to Met allele carriers. Finally, the associations between brain activation, bFC (among various regions), and WM performance were identified only in specific genotype groups of the female participants. These findings provide new insights into the role of COMT Val¹⁵⁸Met gene polymorphism in brain function, particularly its female-specific nature.

Unlabelled

The accurate measurement of β-amyloid (Aβ) change using amyloid PET imaging is important for Alzheimer disease research and clinical trials but poses several unique challenges. In particular, reference region measurement instability may lead to spurious changes in cortical regions of interest. To optimize our ability to measure (18)F-florbetapir longitudinal change, we evaluated several candidate regions of interest and their influence on cortical florbetapir change over a 2-y period in participants from the Alzheimer Disease Neuroimaging Initiative (ADNI).

Methods

We examined the agreement in cortical florbetapir change detected using 6 candidate reference regions (cerebellar gray matter, whole cerebellum, brain stem/pons, eroded subcortical white matter [WM], and 2 additional combinations of these regions) in 520 ADNI subjects. We used concurrent cerebrospinal fluid Aβ1-42 measurements to identify subgroups of ADNI subjects expected to remain stable over follow-up (stable Aβ group; n = 14) and subjects expected to increase (increasing Aβ group; n = 91). We then evaluated reference regions according to whether cortical change was minimal in the stable Aβ group and cortical retention increased in the increasing Aβ group.

Results

There was poor agreement across reference regions in the amount of cortical change observed across all 520 ADNI subjects. Within the stable Aβ group, however, cortical florbetapir change was 1%-2% across all reference regions, indicating high consistency. In the increasing Aβ group, cortical increases were significant with all reference regions. Reference regions containing WM (as opposed to cerebellum or pons) enabled detection of cortical change that was more physiologically plausible and more likely to increase over time.

Conclusion

Reference region selection has an important influence on the detection of florbetapir change. Compared with cerebellum or pons alone, reference regions that included subcortical WM resulted in change measurements that are more accurate. In addition, because use of WM-containing reference regions involves dividing out cortical signal contained in the reference region (via partial-volume effects), use of these WM-containing regions may result in more conservative estimates of actual change. Future analyses using different tracers, tracer-kinetic models, pipelines, and comparisons with other biomarkers will further optimize our ability to accurately measure Aβ changes over time.

Critical to development of new therapies for Alzheimer's disease (AD) is the ability to detect clinical or pathological change over time. Clinical outcome measures typically used in therapeutic trials have unfortunately proven to be relatively variable and somewhat insensitive to change in this slowly progressive disease. For this reason, development of surrogate biomarkers that identify significant disease-associated brain changes are necessary to expedite treatment development in AD. Since AD pathology is present in the brain many years prior to clinical manifestation, ideally we want to develop biomarkers of disease that identify abnormal brain structure or function even prior to cognitive decline. Magnetic resonance imaging, fluorodeoxyglucose positron emission tomography, new amyloid imaging techniques, and spinal fluid markers of AD all have great potential to provide surrogate endpoint measures for AD pathology. The Alzheimer's disease neuroimaging initiative (ADNI) was developed for the distinct purpose of evaluating surrogate biomarkers for drug development in AD. Recent evidence from ADNI demonstrates that imaging may provide more sensitive, and earlier, measures of disease progression than traditional clinical measures for powering clinical drug trials in Alzheimer's disease. This review discusses recently presented data from the ADNI dataset, and the importance of imaging in the future of drug development in AD.