Transplant Coordinators' Perceived Impact of Availability of Multiple Generic Immunosuppression Therapies on Patients, Workload, and Posttransplant Maintenance Therapy

Background. No studies have evaluated the impact of multiple generic immunosuppression medications on transplant coordinators (TCs) and patients. Methods. A cross-sectional, multicenter online survey of TCs managing transplant recipients' outpatient immunosuppression was undertaken to assess TCs' perceptions of the impact of multiple generic immunosuppression therapies on patients and workload. Results. Forty-six of 106 transplant centers contacted (43%) completed the survey, with usable information from 34 TCs (53% in centers performing >100 solid organ transplants annually, 82% registered nurses, and 68% with >5-year experience working with transplant patients). TCs indicated that “change in strength,� “switching from branded to generics,� “heavy pill burden,� and “switching from one generic to another� were the four most frequent reasons for patient confusion regarding immunosuppression. TCs reported increased patient confusion over the previous year for patients on generic immunosuppression therapy: 44% answered ≥3 patient calls/day regarding confusion over immunosuppression therapy. Most TCs indicated increased workload since the introduction of generic immunosuppression therapy. TCs perceived “acute rejection rates,� “rate of graft loss,� and “poor patient adherence� as the three most likely consequences of multiple generic immunosuppression therapy. Conclusion. TCs associated availability of multiple generic immunosuppression therapy with increased patient confusion and time spent addressing patient concerns

Species-specific low-temperature thresholds for winter active bats in North Carolina

Low winter-temperatures drive hibernation and migration in bats in temperate regions, which in turn can influence mortality via white-nose syndrome (WNS) and wind turbine interactions. However, the low-temperature during winter at which bats are able to be active remains unknown. I describe the species-specific winter low-temperature thresholds (TLT) for bat presence across the state of North Carolina (NC), USA. I defined the TLT as the sunset temperature (Ta) at which there was a certain probability of presence for that night and tested 10% (TLT 10) and 25% (TLT 25) levels. I studied two migratory species, Lasionycteris noctivagans and Lasiurus cinereus, and two cave hibernating species, Perimyotis subflavus and Eptesicus fuscus. I predicted that different species of bats would have different TLT , and that larger species would have lower TLT. I also predicted that migratory bats would have lower TLT than cave hibernating bats. I acoustically monitored bat activity from sunset to sunrise in the winter (December to February) of 2017 and 2018, across a large Ta gradient (mean winter temperatures -0.1°C to 11.6°C). I found all species to be present in the winter: L. noctivagans on 611 detector nights, E. fuscus on 242 detector nights, P. subflavus on 155 detector nights, and L. cinereus on 111 detector nights. In contrast to my prediction for migratory bats, the smaller bodied L. noctivagans had a lower TLT (TLT 10 1.01 °C Ta ,TLT 25 7.27°C Ta) than the larger bodied L. cinereus (TLT 10 13.76°C Ta ,TLT 25 18.79°C Ta). In support of my prediction I found that at low Ta, body mass is important in predicting probability of presence in cave hibernating species at TLT 10 (E. fuscus 9.65°C Ta, P. subflavus12.53 °C Ta), but as the Ta warms that effect weakens at TLT 25 (E. fuscus 16.92°C Ta, P. subflavus 17.76 °C Ta ). I found lower TLT 10 in species less affected by WNS, suggesting that behavioral adaptations to low winter Ta affect WNS susceptibility. My results can be used to model the progression of WNS in the southern USA, as well as improve our understanding of winter L. cinereus wind turbine collisions in NC. [This abstract has been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]]]> 2019 Bats $z North Carolina Winter$z North Carolina Climatic changes Hoary bat $x Migration Silver-haired bat$x Migration Tri-colored bat $x Hibernation Big brown bat$x Hibernation English http://libres.uncg.edu/ir/uncg/f/Parker_uncg_0154M_12784.pdf oai:libres.uncg.edu/26587 2019-07-17T16:36:28Z UNCG Comparing three multilevel frameworks for the detection of differential item functioning NC DOCKS at The University of North Carolina at Greensboro Patton, Elizabeth Adele <![CDATA[Multilevel data complicates the accumulation of validation evidence. Using a unilevel approach to differential item functioning in the presence of multilevel data is both a theoretically and statistically unsound method. This simulation study compares three multilevel frameworks for the detection of differential item functioning. The methods compared were the Beggs Mantel-Haenszel adjustment, the multilevel Rasch model, and the SIBTEST bootstrapped standard error adjustment. Five conditions were varied in this study: the magnitude of DIF, the social-unit level sample size, the presence of impact, the degree of correlation within clusters, and the ratio of the reference to focal group. The results suggest that the Beggs Mantel-Haenszel adjustment is superior when analyzing Type I error and power rates. However, the multilevel Rasch model produced more accurate and precise estimates of effect size. Additionally, the multilevel Rasch model has the potential to provide more nuanced information regarding the causes of item bias

In vitro and in vivo evaluation of human adenovirus type 49 as a vector for therapeutic applications

The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-exist-ing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile— remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a rela-tively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

Measuring Dysfunctional Attitudes in the General Population: The Dysfunctional Attitude Scale (form A) Revised

The Dysfunctional Attitude Scale (DAS) was designed to measure the intensity of dysfunctional attitudes, a hallmark feature of depression. Various exploratory factor analytic studies of the DAS form A (DAS-A) yielded mixed results. The current study was set up to compare the fit of various factor models. We used a large community sample (N = 8,960) to test the previously proposed factor models of the DAS-A using confirmatory factor analysis. The retained model of the DAS-A was subjected to reliability and validity analyses. All models showed good fit to the data. Finally, a two-factor solution of the DAS-A was retained, consisting of 17 items. The factors demonstrated good reliability and convergent construct validity. Significant associations were found with depression. Norm-scores were presented. We advocate the use of a 17-item DAS-A, which proved to be useful in measuring dysfunctional beliefs. On the basis of previous psychometric studies, our study provides solid evidence for a two-factor model of the DAS-A, consisting of ‘dependency’ and ‘perfectionism/performance evaluation’

The death and the resurrection of (psy)critique: the case of neuroeducation

A rapidly emerging hegemonic neuro-culture and a booming neural subjectivity signal the entry point for an inquiry into the status of the signifier neuro as a universal passe-partout. The wager of this paper is that the various (mis)appropriations of the neurosciences in the media and in academia itself point to something essential, if not structural, in connection with both the discipline of the neurosciences and the current socio-cultural and ideological climate. Starting from the case of neuroeducation (the application of neuroscience within education), the genealogy of the neurological turn is linked to the history of psychology and its inextricable bond with processes of psychologisation. If the neurological turn risks not merely neglecting the dimension of critique, but also obviating its possibility, then revivifying a psy-critique (understanding the academified modern subject as grounded in the scientific point of view from nowhere) might be necessary in order to understand today’s neural subjectivity and its place within current biopolitics

Inhibition of the inositol kinase Itpkb augments calcium signaling in lymphocytes and reveals a novel strategy to treat autoimmune disease

Emerging approaches to treat immune disorders target positive regulatory kinases downstream of antigen receptors with small molecule inhibitors. Here we provide evidence for an alternative approach in which inhibition of the negative regulatory inositol kinase Itpkb in mature T lymphocytes results in enhanced intracellular calcium levels following antigen receptor activation leading to T cell death. Using Itpkb conditional knockout mice and LMW Itpkb inhibitors these studies reveal that Itpkb through its product IP4 inhibits the Orai1/Stim1 calcium channel on lymphocytes. Pharmacological inhibition or genetic deletion of Itpkb results in elevated intracellular Ca2+ and induction of FasL and Bim resulting in T cell apoptosis. Deletion of Itpkb or treatment with Itpkb inhibitors blocks T-cell dependent antibody responses in vivo and prevents T cell driven arthritis in rats. These data identify Itpkb as an essential mediator of T cell activation and suggest Itpkb inhibition as a novel approach to treat autoimmune disease

Disc reflection and a possible disc wind during a soft X-ray state in the neutron star low-mass X-ray binary 1RXS J180408.9-342058

1RXS J180408.9–342058 is a transient neutron star low-mass X-ray binary that exhibited a bright accretion outburst in 2015. We present $\textit{NuSTAR}$, $\textit{Swift}$, and $\textit{Chandra}$ observations obtained around the peak brightness of this outburst. The source was in a soft X-ray spectral state and displayed an X-ray luminosity of $L_\text{X}$ $\simeq$ (2–3) × 10$^{37}$($D$/5.8 kpc)$^2$ erg s$^{−1}$ (0.5–10 keV). The $\textit{NuSTAR}$ data reveal a broad Fe–K emission line that we model as relativistically broadened reflection to constrain the accretion geometry. We found that the accretion disc is viewed at an inclination of $i$ $\simeq$ 27$^{\circ}$–35$^{\circ}$ and extended close to the neutron star, down to $R_\text{in}$ $\simeq$ 5–7.5 gravitational radii ($\simeq$11–17 km). This inner disc radius suggests that the neutron star magnetic field strength is $B$ $\lesssim$ 2 × 10$^8$ G. We find a narrow absorption line in the $\textit{Chandra}$/HEG data at an energy of $\simeq$7.64 keV with a significance of $\simeq$4.8$\sigma$. This feature could correspond to blueshifted Fe $\small \text{XXVI}$ and arise from an accretion disc wind, which would imply an outflow velocity of $v_\text{out}$ $\simeq$0.086$c$ ($\simeq$25 800 km s$^{−1}$). However, this would be extreme for an X-ray binary and it is unclear if a disc wind should be visible at the low inclination angle that we infer from our reflection analysis. Finally, we discuss how the X-ray and optical properties of 1RXS J180408.9–342058 are consistent with a relatively small ($P_\text{orb}$ $\lesssim$ 3 h) binary orbit.ND is supported by an NWO/Vidi grant and an EU Marie Curie Intra-European fellowship under contract no. FP-PEOPLE-2013-IEF-627148. DA acknowledges support from the Royal Society. JCAMJ is supported by an Australian Research Council (ARC) Future Fellowship (FT140101082) and an ARC Discovery Grant (DP120102393). RW and AP are supported by an NWO/TOP grant, module 1, awarded to RW. COH is supported by an NSERC Discovery Grant. ATD is supported by an NWO/Veni grant. JWTH is supported by NWO/Vidi and ERC/starting (337062) grants

A spectroscopic study of the structure of amorphous hydrogenated carbon

A range of amorphous hydrogenated carbon (a-C:H) samples have been studied using inelastic neutron spectroscopy (INS) and Fourier transform infrared (FTIR) spectroscopy. Using these complementary techniques, the bonding environments of both carbon and hydrogen can be probed in some detail, with the INS data providing not only qualitative but also quantitative information. By comparing the data from each of the samples we have been able to examine the effects of different deposition conditions, i.e. precursor gas, deposition energy and deposition method, on the atomic-scale structure of a-C:H