Dissociating Statistically Determined Normal Cognitive Abilities and Mild Cognitive Impairment Subtypes with DCTclock.

OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia. METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning. RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total combined command/copy scores out of all groups. The mx/dysMCI group scored lower than the CN group on all command indices ( CONCLUSIONS: These results suggest that DCTclock command/copy parameters can dissociate CN, SbCI, and MCI subtypes. The larger effect sizes for command clock indices suggest these metrics are sensitive in detecting early cognitive decline. Additional research with a larger sample is warranted

The dynamic crossover in water does not require bulk water

Many of the anomalous properties of water may be explained by invoking a second critical point that terminates the coexistence line between the low- and high-density amorphous states in the liquid. Direct experimental evidence of this point, and the associated polyamorphic liquid–liquid transition, is elusive as it is necessary for liquid water to be cooled below its homogeneous-nucleation temperature. To avoid crystallization, water in the eutectic LiCl solution has been studied but then it is generally considered that “bulk” water cannot be present. However, recent computational and experimental studies observe cooperative hydration in which case it is possible that sufficient hydrogen-bonded water is present for the essential characteristics of water to be preserved. For femtosecond optical Kerr-effect and nuclear magnetic resonance measurements, we observe in each case a fractional Stokes–Einstein relation with evidence of the dynamic crossover appearing near 220 K and 250 K respectively. Spectra obtained in the glass state also confirm the complex nature of the hydrogen-bonding modes reported for neat room-temperature water and support predictions of anomalous diffusion due to “worm-hole” structure

Visual and Verbal Serial List Learning in Patients with Statistically-Determined Mild Cognitive Impairment.

Background and Objective: Prior research with patients with mild cognitive impairment (MCI) suggests that visual versus verbal episodic memory test performance may be more sensitive to emergent illness. However, little research has examined visual versus verbal episodic memory performance as related to MCI subtypes. Research Design and Methods: Patients were diagnosed with non-MCI, amnestic MCI (aMCI), and combined mixed/dysexecutive MCI (mixed/dys MCI). Visual and verbal episodic memory were assessed with the Brief Visuospatial Memory Test-Revised (BVMT-R) and the 12-word Philadelphia (repeatable) Verbal Learning Test (P[r]VLT), respectively. Results: BVMT-R and P(r)VLT scores yielded similar between-group patterns of performance. Non-MCI patients scored better than other groups on all parameters. aMCI and mixed/dys MCI did not differ on immediate or delayed free recall. Both delayed BVMT-R and P(r)VLT recognition test performance dissociated all three groups. Logistic regression analyses found that BVMT-R delayed free recall and delayed recognition scores correctly classified more patients with MCI (75.40%) than analogous P(r)VLT scores (66.20%). Visual versus verbal memory within-group analyses found no differences among non-MCI patients; P(r)VLT immediate free recall was worse among aMCI patients, but BVMT-R immediate free recall and delayed recognition were worse among mixed/dys MCI patients. Discussion and Implications: Between-group analyses found convergent patterns of performance such that both tests identified elements of amnesia. However, logistic and within-group analyses found differing performance patterns suggesting that impaired visual episodic memory performance may be specific to emergent illness in mixed/dys MCI. Complementary but divergent neurocognitive networks may underlie visual versus verbal episodic memory performance in some patients with MCI

Climate Change Impacts on Iowa, 2010

Climate change is already affecting the way Iowans live and work. Without action to mitigate these effects, our future responses will become more complex and costly . The following policy recommendations are offered as initial steps to help safeguard our state’s economy, environment, and residents

Sensitivity of Metrics of Phylogenetic Structure to Scale, Source of Data and Species Pool of Hummingbird Assemblages along Elevational Gradients

Patterns of phylogenetic structure of assemblages are increasingly used to gain insight into the ecological and evolutionary processes involved in the assembly of co-occurring species. Metrics of phylogenetic structure can be sensitive to scaling issues and data availability. Here we empirically assess the sensitivity of four metrics of phylogenetic structure of assemblages to changes in (i) the source of data, (ii) the spatial grain at which assemblages are defined, and (iii) the definition of species pools using hummingbird (Trochilidae) assemblages along an elevational gradient in Colombia. We also discuss some of the implications in terms of the potential mechanisms driving these patterns. To explore how source of data influence phylogenetic structure we defined assemblages using three sources of data: field inventories, museum specimens, and range maps. Assemblages were defined at two spatial grains: coarse-grained (elevational bands of 800-m width) and fine-grained (1-km2 plots). We used three different species pools: all species contained in assemblages, all species within half-degree quadrats, and all species either above or below 2000 m elevation. Metrics considering phylogenetic relationships among all species within assemblages showed phylogenetic clustering at high elevations and phylogenetic evenness in the lowlands, whereas those metrics considering only the closest co-occurring relatives showed the opposite trend. This result suggests that using multiple metrics of phylogenetic structure should provide greater insight into the mechanisms shaping assemblage structure. The source and spatial grain of data had important influences on estimates of both richness and phylogenetic structure. Metrics considering the co-occurrence of close relatives were particularly sensitive to changes in the spatial grain. Assemblages based on range maps included more species and showed less phylogenetic structure than assemblages based on museum or field inventories. Coarse-grained assemblages included more distantly related species and thus showed a more even phylogenetic structure than fine-grained assemblages. Our results emphasize the importance of carefully selecting the scale, source of data and metric used in analysis of the phylogenetic structure of assemblages

A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis

OBJECTIVE: To determine the steroid-sparing effect of methotrexate (MTX) in patients with symptomatic generalized myasthenia gravis (MG). METHODS: We performed a 12-month multicenter, randomized, double-blind, placebo-controlled trial of MTX 20 mg orally every week vs placebo in 50 acetylcholine receptor antibody-positive patients with MG between April 2009 and August 2014. The primary outcome measure was the prednisone area under the dose-time curve (AUDTC) from months 4 to 12. Secondary outcome measures included 12-month changes of the Quantitative Myasthenia Gravis Score, the Myasthenia Gravis Composite Score, Manual Muscle Testing, the Myasthenia Gravis Quality of Life, and the Myasthenia Gravis Activities of Daily Living. RESULTS: Fifty-eight patients were screened and 50 enrolled. MTX did not reduce the month 4-12 prednisone AUDTC when compared to placebo (difference MTX - placebo: -488.0 mg, 95% confidence interval -2,443.4 to 1,467.3, p = 0.26); however, the average daily prednisone dose decreased in both groups. MTX did not improve secondary measures of MG compared to placebo over 12 months. Eight participants withdrew during the course of the study (1 MTX, 7 placebo). There were no serious MTX-related adverse events. The most common adverse event was nonspecific pain (19%). CONCLUSIONS: We found no steroid-sparing benefit of MTX in MG over 12 months of treatment, despite being well-tolerated. This study demonstrates the challenges of conducting clinical trials in MG, including difficulties with recruitment, participants improving on prednisone alone, and the need for a better understanding of outcome measure variability for future clinical trials. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with generalized MG MTX does not significantly reduce the prednisone AUDTC over 12 months of therapy

Recruitment and Activation of Pancreatic Stellate Cells from the Bone Marrow in Pancreatic Cancer: A Model of Tumor-Host Interaction

BACKGROUND AND AIMS: Chronic pancreatitis and pancreatic cancer are characterised by extensive stellate cell mediated fibrosis, and current therapeutic development includes targeting pancreatic cancer stroma and tumor-host interactions. Recent evidence has suggested that circulating bone marrow derived stem cells (BMDC) contribute to solid organs. We aimed to define the role of circulating haematopoietic cells in the normal and diseased pancreas. METHODS: Whole bone marrow was harvested from male β-actin-EGFP donor mice and transplanted into irradiated female recipient C57/BL6 mice. Chronic pancreatitis was induced with repeat injections of caerulein, while carcinogenesis was induced with an intrapancreatic injection of dimethylbenzanthracene (DMBA). Phenotype of engrafted donor-derived cells within the pancreas was assessed by immunohistochemistry, immunofluorescence and in situ hybridisation. RESULTS: GFP positive cells were visible in the exocrine pancreatic epithelia from 3 months post transplantation. These exhibited acinar morphology and were positive for amylase and peanut agglutinin. Mice administered caerulein developed chronic pancreatitis while DMBA mice exhibited precursor lesions and pancreatic cancer. No acinar cells were identified to be donor-derived upon cessation of cerulein treatment, however rare occurrences of bone marrow-derived acinar cells were observed during pancreatic regeneration. Increased recruitment of BMDC was observed within the desmoplastic stroma, contributing to the activated pancreatic stellate cell (PaSC) population in both diseases. Expression of stellate cell markers CELSR3, PBX1 and GFAP was observed in BMD cancer-associated PaSCs, however cancer-associated, but not pancreatitis-associated BMD PaSCs, expressed the cancer PaSC specific marker CELSR3. CONCLUSIONS: This study demonstrates that BMDC can incorporate into the pancreas and adopt the differentiated state of the exocrine compartment. BMDC that contribute to the activated PaSC population in chronic pancreatitis and pancreatic cancer have different phenotypes, and may play important roles in these diseases. Further, bone marrow transplantation may provide a useful model for the study of tumor-host interactions in cancer and pancreatitis

Archiving primary data: solutions for long-term studies

The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers