Musical Tasks Targeting Preserved and Impaired Functions in Two Dementias

Studies of musical abilities in dementia have for the most part been rather general assessments of abilities, for instance, assessing retention of music learned premorbidly. Here, we studied patients with dementias with contrasting cognitive profiles to explore specific aspects of music cognition under challenge. Patients suffered from Alzheimer\u27s disease (AD), in which a primary impairment is in forming new declarative memories, or Lewy body disease (PD/LBD), a type of parkinsonism in which executive impairments are prominent. In the AD patients, we examined musical imagery. Behavioral and neural evidence confirms involvement of perceptual networks in imagery, and these are relatively spared in early stages of the illness. Thus, we expected patients to have relatively intact imagery in a mental pitch comparison task. For the LBD patients, we tested whether executive dysfunction would extend to music. We probed inhibitory skills by asking for a speeded pitch or timbre judgment when the irrelevant dimension was held constant or also changed. Preliminary results show that AD patients score similarly to controls in the imagery tasks, but PD/LBD patients are impaired relative to controls in suppressing some irrelevant musical dimensions, particularly when the required judgment varies from trial to trial. 2014 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences

Motor Qualification for Long-Duration Mars Missions

Qualification of motors for deep space under extreme thermal environments to be encountered during the Mars Science Laboratory (MSL) mission is required to verify the reliability and validate mission assurance requirements. The motor assembly must survive all ground operations, plus the nominal 670 Martian-day (or sol) mission that includes summer and winter seasons of the Mars environment. The motor assembly was tested and characterized under extreme temperature conditions with reference to hardware requirements. The motor assembly has been proved to be remarkably robust and displayed no sign of degradation due to the 3 X (three times per JPL design principles) thermal environmental exposure to the punishing Mars surface operations cycles. The motor characteristics obtained before, during, and post-test comparisons for the surface operations cycles are within measurement error of one another. The motors withstood/survived 2,010 extreme temperature cycles with a Delta T of 190 C deep temperature cycles, representing three times the expected thermal cycling exposure during the MSL surface operations. The qualification test hardware elements (A200 motor assembly, encoders, and resolver) have not shown any signs of degradation due to the PQV (Package Qualification and Verification) testing. The test hardware has demonstrated sufficient life to survive the deep thermal cycles associated with MSL mission surface operations for three lives

Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma.

Funder: NIHR Cambridge Biomedical Research CentreFunder: Addenbrooke’s Charitable TrustFunder: National Institute for Health Research (NIHR)Funder: Mark Foundation For Cancer ResearchFunder: Cambridge Commonwealth, European and International TrustFunder: Cancer Research UKFunder: Cambridge Clinical Trials UnitFunder: Cancer Research UK Cambridge CentreFunder: Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and ManchesterFunder: Cambridge Experimental Cancer Medicine CentrePURPOSE: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. METHOD: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. RESULTS: 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p<0.001). CONCLUSIONS: Physiological imaging confirmed efficacy of the anti-angiogenic agent 12 days after initiating therapy and demonstrated response to treatment. The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in mRCC undergoing nephrectomy, however, no parameter predicted OS. TRIAL REGISTRATION: EudraCtNo: 2005-004502-82

Association, effects and validation of polymorphisms within the NCAPG - LCORL locus located on BTA6 with feed intake, gain, meat and carcass traits in beef cattle

<p>Abstract</p> <p>Background</p> <p>In a previously reported genome-wide association study based on a high-density bovine SNP genotyping array, 8 SNP were nominally associated (<it>P </it>≤ 0.003) with average daily gain (ADG) and 3 of these were also associated (<it>P </it>≤ 0.002) with average daily feed intake (ADFI) in a population of crossbred beef cattle. The SNP were clustered in a 570 kb region around 38 Mb on the draft sequence of bovine chromosome 6 (BTA6), an interval containing several positional and functional candidate genes including the bovine <it>LAP3, NCAPG</it>, and <it>LCORL </it>genes. The goal of the present study was to develop and examine additional markers in this region to optimize the ability to distinguish favorable alleles, with potential to identify functional variation.</p> <p>Results</p> <p>Animals from the original study were genotyped for 47 SNP within or near the gene boundaries of the three candidate genes. Sixteen markers in the <it>NCAPG-LCORL </it>locus displayed significant association with both ADFI and ADG even after stringent correction for multiple testing (P ≤ 005). These markers were evaluated for their effects on meat and carcass traits. The alleles associated with higher ADFI and ADG were also associated with higher hot carcass weight (HCW) and ribeye area (REA), and lower adjusted fat thickness (AFT). A reduced set of markers was genotyped on a separate, crossbred population including genetic contributions from 14 beef cattle breeds. Two of the markers located within the <it>LCORL </it>gene locus remained significant for ADG (P ≤ 0.04).</p> <p>Conclusions</p> <p>Several markers within the <it>NCAPG-LCORL </it>locus were significantly associated with feed intake and body weight gain phenotypes. These markers were also associated with HCW, REA and AFT suggesting that they are involved with lean growth and reduced fat deposition. Additionally, the two markers significant for ADG in the validation population of animals may be more robust for the prediction of ADG and possibly the correlated trait ADFI, across multiple breeds and populations of cattle.</p

Patterns of patient-reported symptoms and association with sociodemographic and systemic sclerosis disease characteristics: a scleroderma Patient-centered Intervention Network (SPIN) Cohort cross-sectional study

Background Systemic sclerosis is a heterogenous disease in which little is known about patterns of patient-reported symptom clusters. We aimed to identify classes of individuals with similar anxiety, depression, fatigue, sleep disturbance, and pain symptoms and to evaluate associated sociodemographic and disease-related characteristics. Methods This multi-centre cross-sectional study used baseline data from Scleroderma Patient-centered Intervention Network Cohort participants enrolled from 2014 to 2020. Eligible participants completed the PROMIS-29 v2.0 measure. Latent profile analysis was used to identify homogeneous classes of participants based on patterns of anxiety, depression, fatigue, sleep disturbance, and pain scores. Sociodemographic and disease-related characteristics were compared across classes. Findings Among 2212 participants, we identified five classes, including four classes with “Low” (565 participants, 26%), “Normal” (651 participants, 29%), “High” (569 participants, 26%), or “Very High” (193 participants, 9%) symptom levels across all symptoms. Participants in a fifth class, “High Fatigue/Sleep/Pain and Low Anxiety/Depression” (234 participants, 11%) had similar levels of fatigue, sleep disturbance, and pain as in the “High” class but low anxiety and depression symptoms. There were significant and substantive trends in sociodemographic characteristics (age, education, race or ethnicity, marital or partner status) and increasing disease severity (diffuse disease, tendon friction rubs, joint contractures, gastrointestinal symptoms) across severity-based classes. Disease severity and sociodemographic characteristics of “High Fatigue/Sleep/Pain and Low Anxiety/Depression” class participants were similar to the “High” severity class. Interpretation Most people with systemic sclerosis can be classified by levels of patient-reported symptoms, which are consistent across symptoms and highly associated with sociodemographic and disease-related variables, except for one group which reports low mental health symptoms despite high levels of other symptoms and substantial disease burden. Studies are needed to better understand resilience in systemic sclerosis and to identify and facilitate implementation of cognitive and behavioural strategies to improve coping and overall quality of life

The Application of Novel Research Technologies by the Deep Pelagic Nekton Dynamics of the Gulf of Mexico (DEEPEND) Consortium

The deep waters of the open ocean represent a major frontier in exploration and scientific understanding. However, modern technological and computational tools are making the deep ocean more accessible than ever before by facilitating increasingly sophisticated studies of deep ocean ecosystems. Here, we describe some of the cutting-edge technologies that have been employed by the Deep Pelagic Nekton Dynamics of the Gulf of Mexico (DEEPEND; www.deependconsortium.org) Consortium to study the biodiverse fauna and dynamic physical-chemical environment of the offshore Gulf of Mexico (GoM) from 0 to 1,500 m

Identification of a Small Molecule that Increases Hemoglobin Oxygen Affinity and Reduces SS Erythrocyte Sickling

Small molecules that increase the oxygen affinity of human hemoglobin may reduce sickling of red blood cells in patients with sickle cell disease. We screened 38 700 compounds using small molecule microarrays and identified 427 molecules that bind to hemoglobin. We developed a high-throughput assay for evaluating the ability of the 427 small molecules to modulate the oxygen affinity of hemoglobin. We identified a novel allosteric effector of hemoglobin, di(5-(2,3-dihydro-1,4-benzodioxin-2-yl)-4H-1,2,4-triazol-3-yl)disulfide (TD-1). TD-1 induced a greater increase in oxygen affinity of human hemoglobin in solution and in red blood cells than did 5-hydroxymethyl-2-furfural (5-HMF), N-ethylmaleimide (NEM), or diformamidine disulfide. The three-dimensional structure of hemoglobin complexed with TD-1 revealed that monomeric units of TD-1 bound covalently to β-Cys93 and β-Cys112, as well as noncovalently to the central water cavity of the hemoglobin tetramer. The binding of TD-1 to hemoglobin stabilized the relaxed state (R3-state) of hemoglobin. TD-1 increased the oxygen affinity of sickle hemoglobin and inhibited in vitro hypoxia-induced sickling of red blood cells in patients with sickle cell disease without causing hemolysis. Our study indicates that TD-1 represents a novel lead molecule for the treatment of patients with sickle cell disease