Miracle-dz/UniFAR-FTUs huggingface dataset:
Student nurses' attitudes towards working with older patients.

BACKGROUND The ageing of the United Kingdom (UK) population means that the care of older people will become an increasingly important part of nurses' remit. However, employment statistics suggest that this is an unpopular nursing specialism. This may be due to a number of factors, one of which may be nurses' negative attitudes towards working with older people. This constitutes a potential problem, especially if such attitudes have an impact on the quality of care provided. AIM To examine the attitudes held by student nurses towards working with older patients. METHODS Questionnaires incorporating Likert-type scales, two vignettes and demographic questions were designed using the theory of planned behaviour. These were distributed to 172 student nurses undertaking preregistration nursing courses in the UK during the academic session 2000-2001. RESULTS Student nurses displayed positive intentions towards working with older patients. These were based on their own attitudes and beliefs about what others would wish them to do. Participants believed that their behaviour towards older patients was to a large extent under volitional control. Analysis of the beliefs underlying student nurses' views showed that they differentiated between those participants who had a relatively positive approach to their work with older patients and those with a less positive approach. In addition, the results offered mixed support for the view that more knowledgeable or experienced nurses hold more positive views towards older people. CONCLUSIONS The findings offer some support for previous studies that have looked at the more general issue of attitudes towards older people. However, the results also indicate that a more rigorous and more highly focused approach to the study of such attitudes is required if the research is to be relevant to the issue of working with older patients. The theoretical, methodological and practical implications of the findings are discussed.
Impact of parents' substance misuse on children: an update

Summary We review how research over the past decade both supports existing knowledge about the risk factors that children in the UK affected by parental substance misuse face, and adds to our knowledge about the protective factors, protective processes and evidence of resilience which can reduce the likelihood that children will experience poor outcomes. Further research is needed to understand what areas of resilience are most important to target and how other variables, such as gender or age, may influence how protective factors affect the development of resilience. Longitudinal research is also needed to better understand how an individual's resilience may change over time. Finally, there remain many considerable challenges which practitioners, service providers, commissioners and policy makers face in better meeting the needs of this population of children.
Word boundaries in L2 speech: Evidence from Polish learners of English

Acoustic and perceptual studies investgate B2-level Polish learners’ acquisition of second language (L2) English word-boundaries involving word-initial vowels. In production, participants were less likely to produce glottalization of phrase-medial initial vowels in L2 English than in first language (L1) Polish. Perception studies employing word monitoring and word counting tasks found that glottalization of word-initial vowels had a negligible impact on the processing of L2 word boundaries. Taken together, these experiments suggest that B2-level learners are relatively successful in acquiring word-boundary linking processes that are for the most part absent from L1 Polish, and challenge the notion of an L2 ‘Word Integrity’ constraint. The cross-language interactions observed in these experiments are compatible with the claim that the realization of word-initial vowels is governed by a representational parameter, which may be derived in the Onset Prominence framework.
Regularized Estimation in High Dimensional Time Series under Mixing Conditions

The Lasso is one of the most popular methods in high dimensional statistical learning. Most existing theoretical results for the Lasso, however, require the samples to be iid. Recent work has provided guarantees for the Lasso assuming that the time series is generated by a sparse Vector Auto-Regressive (VAR) model with Gaussian innovations. Proofs of these results rely critically on the fact that the true data generating mechanism (DGM) is a finite-order Gaussian VAR. This assumption is quite brittle: linear transformations, including selecting a subset of variables, can lead to the violation of this assumption. In order to break free from such assumptions, we derive nonasymptotic inequalities for estimation error and prediction error of the Lasso estimate of the best linear predictor without assuming any special parametric form of the DGM. Instead, we rely only on (strict) stationarity and mixing conditions to establish consistency of the Lasso in the following two scenarios: (a) alpha-mixing Gaussian processes, and (b) beta-mixing sub-Gaussian random vectors. Our work provides an alternative proof of the consistency of the Lasso for sparse Gaussian VAR models. But the applicability of our results extends to non-Gaussian and non-linear times series models as the examples we provide demonstrate. In order to prove our results, we derive a novel Hanson-Wright type concentration inequality for beta-mixing sub-Gaussian random vectors that may be of independent interest.
Activation of AMPK in rat hypothalamus participates in cold‐induced resistance to nutrient‐dependent anorexigenic signals

The exposure of homeothermic animals to a cold environment leads to a powerful activation of orexigenic signalling which is accompanied by molecular and functional resistance to insulin‐induced inhibition of feeding. Recent evidence suggests that AMPK participates in nutrient‐dependent control of satiety and adiposity. The objective of the present study was to evaluate the effect of cold exposure upon the molecular activation of AMPK signalling in the hypothalamus of rats. Immunoblotting demonstrated that cold exposure per se is sufficient for inducing, on a time‐dependent basis, the molecular activation of the serine/threonine kinase AMP‐activated protein kinase (AMPK) and inactivation of the acetyl‐CoA carboxylase (ACC). These molecular phenomena were accompanied by resistance to nutrient‐induced inactivation of AMPK and activation of ACC. Moreover, cold‐exposure led to a partial inhibition of a feeding‐induced anorexigenic response, which was paralleled by resistance to insulin‐induced suppression of feeding. Finally, cold exposure significantly impaired insulin‐induced inhibition of AMPK through a mechanism dependent on the molecular cross‐talk between phosphatidylinositol‐3(PI3)‐kinase/Akt and AMPK. In conclusion, increased feeding during cold exposure results, at least in part, from resistance to insulin‐ and nutrient‐dependent anorexigenic signalling in the hypothalamus.
Mechanisms behind the Synergistic Effect of Sirolimus and Imatinib in Preventing Restenosis after Intimal Injury

Background: We have shown that the combination of sirolimus and imatinib synergistically inhibits denudation-induced neointimal hyperplasia in rats. We have now dissected the mechanisms behind this synergy and evaluated its long-term efficacy. Methods: After aortic denudation injury, rats received established submaximal doses of sirolimus (1.0 mg/kg/day), imatinib (10.0 mg/kg/day), the combination of these, or vehicle per os from 3 days before the operation until 14 days after injury. Vessel histology and complete blood counts were monitored until 90 days after injury. Neointimal cell outgrowth, migration and proliferation were evaluated in ex vivo vessel cultures. Quantitative real-time polymerase chain reaction and immunohistochemistry were used for gene and protein expression analysis. Results: The combination therapy caused a synergistic decrease in the number of neointimal nuclei and area throughout the observation period. It also prevented postinjury thrombocytosis and leukocytosis, and almost abolished neointimal cell outgrowth and migration. Furthermore, the combination therapy resulted in upregulation of smooth muscle cell (SMC) markers SM22α and cysteine and glycine-rich protein 2, and of the anti-apoptotic BCL2 mRNA. Conclusions: Combination therapy confers superior long-term vasculoprotection, possibly by inhibition of postoperative thrombocytosis and leukocytosis, inhibition of neointimal cell migration to the injury site and maintenance of cell integrity by inhibition of apoptosis and SMC dedifferentiation.
Physical self-concept and physical activity enjoyment in elementary school children

ABSTRACT The present study examined gender differences and relationships of seven specific domains of physical self-concept (PSC) (Strength, Endurance, Speed, Flexibility, Coordination, Global Sport Competence, and Appearance) and physical activity enjoyment (PAE) in 447 elementary school children by self-report questionnaires. Boys reported higher self-concepts of Strength, Endurance, Speed, Coordination, and Global Sport Competence than girls. Conversely, girls showed higher self-concepts of Flexibility than boys. Moreover, all seven specific domains of children's PSC and PAE were positively interrelated and children's self-concepts of Endurance and Global Sport Competence predicted their PAE. Implications for physical education targeting to enhance children's PSC and PAE are discussed.
Connective tissue growth factor [CTGF]/CCN2 stimulates mesangial cell migration through integrated dissolution of focal adhesion complexes and activation of cell polarization

Connective tissue growth factor [CTGF]/CCN2 is a prototypic member of the CCN family of regulatory proteins. CTGF expression is up‐regulated in a number of fibrotic diseases, including diabetic nephropathy, where it is believed to act as a downstream mediator of TGF‐β function; however, the exact mechanisms whereby CTGF mediates its effects remain unclear. Here, we describe the role of CTGF in cell migration and actin disassembly in human mesangial cells, a primary target in the development of renal glomerulosclerosis. The addition of CTGF to primary mesangial cells induced cell migration and cytoskeletal rearrangement but had no effect on cell proliferation. Cytoskeletal rearrangement was associated with a loss of focal adhesions, involving tyrosine dephosphorylation of focal adhesion kinase and paxillin, increased activity of the protein tyrosine phosphatase SHP‐2, with a concomitant decrease in RhoA and Rac1 activity. Conversely, Cdc42 activity was increased by CTGF. These functional responses were associated with the phosphorylation and translocation of protein kinase C‐ζ to the leading edge of migrating cells. Inhibition of CTGF‐induced protein kinase C‐ζ activity with a myristolated PKC‐ζ inhibitor prevented cell migration. Moreover, transient transfection of human mesangial cells with a PKC‐ζ kinase inactive mutant (dominant negative) expression vector also led to a decrease in CTGF‐induced migration compared with wild‐type. Furthermore, CTGF stimulated phosphorylation and activation of GSK‐3β. These data highlight for the first time an integrated mechanism whereby CTGF regulates cell migration through facilitative actin cytoskeleton disassembly, which is mediated by dephosphorylation of focal adhesion kinase and paxillin, loss of RhoA activity, activation of Cdc42, and phosphorylation of PKC‐ζ and GSK‐3β. These changes indicate that the initial stages of CTGF mediated mesangial cell migration are similar to those involved in the process of cell polarization. These findings begin to shed mechanistic light on the renal diabetic milieu, where increased CTGF expression in the glomerulus contributes to cellular dysfunction.
Effects of locus coeruleus lesions on auditory, long-latency, event- related potentials in monkey

It has previously been demonstrated that monkeys exhibit certain event- related potential (ERP) components showing latency, polarity, and contingency similarities to those observed in humans. In the present study, monkey P300-like components were studied in order to evaluate the hypothesis that the noradrenergic locus coeruleus (LC) system participates in their generation or modulation. ERPs were recorded from untrained squirrel monkeys (Saimiri sciureus) twice a week for 4 weeks before and after bilateral LC lesions and interruption of dorsal bundle (DB) fibers. Stimuli consisted of 2 and 6 kHz tone pips (40 msec duration, 60 dB above nHL) presented once a second in random order. In most sessions, one tone constituted 90% of the stimuli and the other tone 10%, while in some sessions tones were made equiprobable to test the effects of manipulating stimulus probability. LC and DB lesions were made by first localizing the nucleus and creating an electrolytic lesion. Then, the electrode was placed at the anterior pole of the nucleus and a knife cut effected. The extent of damage to LC perikarya and ascending axons was assessed by reconstructing lesions from Nissl- stained sagittal sections through the brain stems. The effect of lesions on cortical noradrenergic axons was immunohistochemically verified utilizing antisera directed against dopamine-B-hydroxylase and tyrosine hydroxylase to label noradrenergic and dopaminergic axons, respectively. The prelesion ERP results replicated previous findings of P300-like components recorded in response to low-probability tones. The postlesion ERP data indicated that following damage to LC cell bodies, combined with interruption of histochemically detectable ascending noradrenergic axons, monkey P300-like potentials exhibited decreased areas, altered brain-surface distribution, and reduced sensitivity to stimulus probability. The correlation between the extent of cell body lesions and percentage reduction in the magnitude of P300-like responses was significant. However, interruption of DB fibers alone did not have similar effects. Neither type of lesion had any effect on amplitudes, latencies, or brain-surface distributions of P52, P172, or N250–900. There was, however, a significant effect on N106. Stimulus probability effects on the frontally distributed P52 and N106 were not altered by the lesions. These data support the hypothesis that the integrity of the LC nucleus and its ascending fibers is important in the generation and modulation of surface-recorded P300-like activity.
Estrogen receptor acting in cis enhances WT and mutant p53 transactivation at canonical and noncanonical p53 target sequences

p53 is a master regulatory, sequence-specific transcription factor that directly controls expression of over 100 genes in response to various stress signals. Transactivation is generally considered to occur through p53 binding to a consensus response element (RE) composed of two 5′-RRRCWWGYYY-3′ decamers. Recently, studying the human angiogenesis-related gene FLT1 we discovered that p53 can mediate limited transactivation at a noncanonical 1/2 site and could synergize with the estrogen receptor (ER) acting in cis at a nearby ER 1/2 site. To address the generality of concerted transactivation by p53 and ER, the 1/2 site in the FLT1 promoter was replaced with a variety of 1/2 sites, as well as canonical weak and strong p53 REs of human target genes. The p53 transactivation of all tested sequences was greatly enhanced by ligand-activated ER acting in cis. Furthermore, enhanced transactivation extends to several cancer-associated p53 mutants with altered function, suggesting ER-dependent mutant p53 activity for at least some REs. The enhanced transactivation was also found with p63 and p73. We propose a general synergistic relationship between p53 family and ER master regulators in transactivation of p53 target canonical and noncanonical REs, which might be poorly responsive to p53 on their own. This relationship greatly expands the transcriptional master network regulated by p53 in terms of genes affected and levels of expression and has implications for the appearance and possible treatments of cancer.
An Efficient Online Algorithm for Dynamic SDN Controller Assignment in Data Center Networks

Software defined networking is increasingly prevalent in data center networks for it enables centralized network configuration and management. However, since switches are statically assigned to controllers and controllers are statically provisioned, traffic dynamics may cause long response time and incur high maintenance cost. To address these issues, we formulate the dynamic controller assignment problem (DCAP) as an online optimization to minimize the total cost caused by response time and maintenance on the cluster of controllers. By applying the randomized fixed horizon control framework, we decompose DCAP into a series of stable matching problems with transfers, guaranteeing a small loss in competitive ratio. Since the matching problem is NP-hard, we propose a hierarchical two-phase algorithm that integrates key concepts from both matching theory and coalitional games to solve it efficiently. Theoretical analysis proves that our algorithm converges to a near-optimal Nash stable solution within tens of iterations. Extensive simulations show that our online approach reduces total cost by about 46%, and achieves better load balancing among controllers compared with static assignment.
The Role of Ethanol and Neuroanatomical Regions in Sensitivity to Delay and Sensitivity to Magnitude of Reward

Relative preference for smaller, sooner rewards over larger, later rewards (“delay discounting”) is increased by acute ethanol. However, it is unknown whether this effect is driven by a difference in sensitivity to the reinforcer delay or a difference in sensitivity to the reinforcer magnitude, because typical delay discounting tasks manipulate both parameters simultaneously. Additionally, it is unknown which brain regions may play a role in these different aspects of delay discounting. To investigate this, two studies were conducted in separate groups of male Long Evans rats. The first examined the effects of acute systemic administration of ethanol on performance in two separate tasks that measured sensitivity to delay and sensitivity to magnitude. The second examined the effects of acute temporary inactivation of the nucleus accumbens core (AcbC) and lateral orbitofrontal cortex (lOFC) on two separate tasks that measured sensitivity to delay and sensitivity to magnitude as well as a delay discounting task. None of the acute manipulations had any effect on the measures of sensitivity to delay or sensitivity to magnitude, in contrast to their effects on delay discounting in previous literature. Nonetheless, there were several additional findings of interest. First, rats with high sensitivity to delay were found to be resistant to the behaviorally suppressant effects of a moderate dose of ethanol (0.9 g/kg). Second, inactivation of the AcbC was found to significantly decrease delay discounting. Furthermore, this effect of AcbC inactivation was found to be most prominent in animals with initially low levels of delay discounting.
Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer

Capan-1 is a well-characterised BRCA2-deficient human cell line isolated from a liver metastasis of a pancreatic adenocarcinoma. Here we report a genome-wide assessment of structural variations and high-depth exome characterization of single nucleotide variants and small insertion/deletions in Capan-1. To identify potential somatic and tumour-associated variations in the absence of a matched-normal cell line, we devised a novel method based on the analysis of HapMap samples. We demonstrate that Capan-1 has one of the most rearranged genomes sequenced to date. Furthermore, small insertions and deletions are detected more frequently in the context of short sequence repeats than in other genomes. We also identify a number of novel mutations that may represent genetic changes that have contributed to tumour progression. These data provide insight into the genomic effects of loss of BRCA2 function.
Recent advances in the treatment of life-threatening, invasive fungal infections

Introduction: Invasive fungal infections (IFIs) pose significant morbidity and are often life-threatening to many high-risk patients. Timely diagnosis and treatment of these infections with optimal therapy is imperative. Areas covered: Advances have been made in diagnostic biomarkers such as peptide nucleic acid fluorescent in situ hybridization, β-D-glucan and galactomannan, although more research is needed in this area to assist with both diagnosis and monitoring for improvement of IFI management. Novel antifungal agents (azole antifungals and echinocandins) are being investigated that have activity against Candida spp. and Aspergillus spp. Optimizing the pharmacodynamics (PD) of our current antifungal therapies through such strategies as continuous infusion of amphotericin B and dose escalation of echinocandins and liposomal formulations of amphotericin B have also been investigated with mixed results. Therapeutic drug monitoring (TDM) shows promise as evident from data with such agents as flucytosine, itraconazole, voriconazole and posaconazole. Expert opinion: The goal for the future of biomarkers in IFIs will be to have excellent sensitivity and specificity to ideally identify a particular fungus causing the infection or eliminate its existence to prevent unnecessary costs, resistance and antifungal usage. In addition, further developments of new antifungals are needed and judicious use of the current regimens needs to be optimized through antifungal PD properties and TDM.
Postmarketing surveillance of the safety of cimetidine: 15‐year mortality report

The pattern of mortality after 15 years of observation is reported among almost 10,000 patients who were taking cimetidine when they were first recruited between 1977 and 1980. Many took the drug for a number of years, some switching to other antisecretory agents as the study progressed. The findings are reassuring and provide no evidence of any long‐term adverse effects of cimetidine which might be detected by monitoring mortality rates. The data have also been used to examine the possible positive relationships between aluminium ingestion and Alzheimer's disease and H. pylori infection and ischaemic heart disease. No significant evidence was obtained in support of the existence of these relationships. © 1998 John Wiley & Sons, Ltd.