Changes in insulin and insulin signaling in Alzheimer\u27s disease: Cause or consequence?

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD

CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition.

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a genetically heterogeneous subtype of B-cell ALL characterized by chromosomal rearrangements and mutations that result in aberrant cytokine receptor and kinase signaling. In particular, chromosomal rearrangements resulting in the overexpression of cytokine receptor-like factor 2 (CRLF2) occur in 50% of Ph-like ALL cases. CRLF2 overexpression is associated with particularly poor clinical outcomes, though the molecular basis for this is currently unknown. Glucocorticoids (GCs) are integral to the treatment of ALL and GC resistance at diagnosis is an important negative prognostic factor. Given the importance of GCs in ALL therapy and the poor outcomes for patients with CRLF2 overexpression, we hypothesized that the aberrant signal transduction associated with CRLF2 overexpression might mediate intrinsic GC insensitivity. To test this hypothesis, we exposed Ph-like ALL cells from patient-derived xenografts to GCs and found that CRLF2 rearranged (CRLF2R) leukemias uniformly demonstrated reduced GC sensitivity in vitro. Furthermore, targeted inhibition of signal transduction with the MEK inhibitor trametinib and the Akt inhibitor MK2206, but not the JAK inhibitor ruxolitinib, was sufficient to augment GC sensitivity. These data suggest that suboptimal GC responses may in part underlie the poor clinical outcomes for patients with CRLF2 overexpression and provide rationale for combination therapy involving GCs and signal transduction inhibitors as a means of enhancing GC efficacy

Personal Financial and Economic Issues for College Students

As students enter college, they typically encounter new responsibilities not experienced beforehand. The various financial decisions that college students encounter are one of the most important. These decisions often require students to educate themselves about banking, employment, budgeting, credit card usage, student loans, credit ratings, different types of debt, and insurance, among other things. This paper addresses those various issues. We offer both information and advice with regard to these issues. Consideration of how various financial events and choices effect the student’s long term goals and opportunities is crucial to developing long-term financial well-being. The ability to make sound decisions regarding personal financial issues will help new graduates emerge from college upon solid financial footing

Psychometric Analysis of the JSPE Nursing Student Version R: Comparison of Senior BSN Students and Medical Students Attitudes toward Empathy in Patient Care

Background. Empathic communication skills are critical to providing high-quality nursing care to holistically understand the patient's perspective. A survey research design was used to address the research questions discussed in this study. Data consisted of responses from nursing students attending accredited programs in the southeastern United Sates using the Jefferson Scale of Physician Empathy Nursing Student Version R (JSPE-R). Findings. Comparisons of the total scores from JSPE Versions S and R yielded similar means and standard deviations with 115 and 114.57, respectively, and standard deviations of 10 and 10.94, respectively. The results of a one-sample t-test failed to render statistical significance (t = −1.22, P = .224), indicating that the overall attitudes of nursing students and medical students are similar. The 25th, 50th, and 75th percentiles and overall instrument reliability were also comparable. Conclusions. This paper supports the emergence of alternative factor analysis structures as applied to nursing students through statistical progression from exploratory factor analysis to confirmatory structures. Implications for practice explore the utility of empathy instruments in nurse education, such as empathy progression through curriculum. As nursing educators, the utility of development of instruments to measure effectiveness of teaching strategies and pedagogy for empathy enhancement in practice is important

Risk Mitigation for Travelers: Managing Endemic and Emerging Threats

International travel continues to increase in numbers and complexity. Despite the availability of pretravel health advice, travelers remain at risk for exposure to common organisms as well as emerging pathogens. With low rates of travel clinic utilization, it is important for the general practitioner to remain aware of the importance of travel health, risk factors unique to individual patients, and evolving threats. This review highlights important considerations when evaluating ill travelers, incorporating emerging infectious threats

Proximity-Coupled Ti/TiN Multilayers for use in Kinetic Inductance Detectors

We apply the superconducting proximity effect in TiN/Ti multi-layer films to tune the critical temperature, Tc, to within 10 mK with high uniformity (less than 15 mK spread) across a 75 mm wafer. Reproducible Tc's are obtained from 0.8 - 2.5 K. These films had high resistivities, > 100 uOhm-cm and internal quality factors for resonators in the GHz range on the order of 100k and higher. Both trilayers of TiN/Ti/TiN and thicker superlattice films were prepared, demonstrating a highly controlled process for films over a wide thickness range. Detectors were fabricated and showed single photon resolution at 1550 nm. The high uniformity and controllability coupled with the high quality factor, kinetic inductance, and inertness of TiN make these films ideal for use in frequency multiplexed kinetic inductance detectors and other potential applications such as nanowire detectors, transition edge sensors and associated quantum information applications

Squeeziness: An information theoretic measure for avoiding fault masking

Copyright @ 2012 ElsevierFault masking can reduce the effectiveness of a test suite. We propose an information theoretic measure, Squeeziness, as the theoretical basis for avoiding fault masking. We begin by explaining fault masking and the relationship between collisions and fault masking. We then define Squeeziness and demonstrate by experiment that there is a strong correlation between Squeeziness and the likelihood of collisions. We conclude with comments on how Squeeziness could be the foundation for generating test suites that minimise the likelihood of fault masking

White-tailed Deer (\u3ci\u3eOdocoileus virginianus\u3c/i\u3e) Subsidize Gray Wolves (\u3ci\u3eCanis lupus\u3c/i\u3e) During a Moose (\u3ci\u3eAlces americanus\u3c/i\u3e) Decline: A Case of Apparent Competition?

Moose (Alces americanus) in northeastern Minnesota have declined by 55% since 2006. Although the cause is unresolved, some studies have suggested that Gray Wolves (Canis lupus) contributed to the decline. After the Moose decline, wolves could either decline or switch prey. To determine which occurred in our study area, we compared winter wolf counts and summer diet before and after the Moose decline. While wolf numbers in our study area nearly doubled from 23 in winter 2002 to an average of 41 during winters 2011–2013, calf:cow ratios (the number of calves per cow observed during winter surveys) in the wider Moose range more than halved from 0.93 in 2002 to an average of 0.31 during 2011–2013. Compared to summer 2002, wolves in summers 2011–2013 consumed fewer Moose and more White-tailed Deer (Odocoileus virginianus). While deer densities were similar during each period, average vulnerability, as reflected by winter severity, was greater during 2011–2013 than 2002, probably explaining the wolf increase. During the wolf increase Moose calves remained a summer food item. These findings suggest that in part of the Moose range, deer subsidized wolf numbers while wolves also preyed on Moose calves. This contributed to a Moose decline and is a possible case of apparent competition and inverse-density-dependent predation

Evaluation of a Formula that Categorizes Female Gray Wolf Breeding Status by Nipple Size

The proportion by age class of wild Canis lupus (Gray Wolf) females that reproduce in any given year remains unclear; thus, we evaluated the applicability to our long-term (1972–2013) data set of the Mech et al. (1993) formula that categorizes female Gray Wolf breeding status by nipple size and time of year. We used the formula to classify Gray Wolves from 68 capture events into 4 categories (yearling, adult non-breeder, former breeder, current breeder). To address issues with small sample size and variance, we created an ambiguity index to allow some Gray Wolves to be classed into 2 categories. We classified 20 nipple measurements ambiguously: 16 current or former breeder, 3 former or adult non-breeder, and 1 yearling or adult non-breeder. The formula unambiguously classified 48 (71%) of the nipple measurements; based on supplemental field evidence, at least 5 (10%) of these were incorrect. When used in conjunction with an ambiguity index we developed and with corrections made for classifications involving very large nipples, and supplemented with available field evidence, the Mech et al. (1993) formula provided reasonably reliable classification of breeding status in wild female Gray Wolves

Yellowstone wolf (\u3ci\u3eCanis lupus\u3c/i\u3e) density predicted by elk (\u3ci\u3eCervus elaphus\u3c/i\u3e) biomass

The Northern Range (NR) of Yellowstone National Park (YNP) hosts a higher prey biomass density in the form of elk (Cervus elaphus L., 1758) than any other system of gray wolves (Canis lupus L., 1758) and prey reported. Therefore, it is important to determine whether that wolf–prey system fits a long-standing model relating wolf density to prey biomass. Using data from 2005 to 2012 after elk population fluctuations dampened 10 years subsequent to wolf reintroduction, we found that NR prey biomass predicted wolf density. This finding and the trajectory of the regression extend the validity of the model to prey densities 19% higher than previous data and suggest that the model would apply to wolf–prey systems of even higher prey biomass. Le domaine nord (Northern Range; NR) du parc national de Yellowstone (YNP) contient une biomasse de proies de plus grande densité, représentée par les wapitis (Cervus elaphus L., 1758), que tout autre système de loups gris (Canis lupus L., 1758) et proies connu. Il importe donc de déterminer si le système loups–proies concorde avec un modèle établi de longue date qui relie la densité des loups a` la biomasse des proies. En nous servant de données de 2005 a` 2012 après l’atténuation sur une période de 10 ans des fluctuations de la population de wapitis a` la suite de la réintroduction des loups, nous avons constaté que la biomasse des proies du NR prédisait la densité des loups. Cette constatation et la trajectoire de la régression élargissent la validité du modèle a` des densités de proies de 19 % supérieures aux données antérieures et donnent a` penser que le modèle s’appliquerait a` des systèmes loups–proies de biomasse de proies encore plus grande