Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study.

BACKGROUND Temsirolimus (CCI-779) is a small-molecule inhibitor of the mammalian target of rapamycin (mTOR) and represents a rational therapeutic target against glioblastoma multiforme (GBM). METHODS Recurrent GBM patients with < or = 1 chemotherapy regimen for progressive disease were eligible. Temsirolimus was administered in a 250-mg intravenous dose weekly. RESULTS Sixty-five patients were treated. The incidence of grade 3 or higher nonhematologic toxicity was 51%, and consisted mostly of hypercholesterolemia (11%), hypertriglyceridemia (8%), and hyperglycemia (8%). Grade 3 hematologic toxicity was observed in 11% of patients. Temsirolimus peak concentration (Cmax), and sirolimus Cmax and area under the concentration-time curve were decreased in patients receiving p450 enzyme-inducing anticonvulsants (EIACs) by 73%, 47%, and 50%, respectively, but were still within the therapeutic range of preclinical models. Twenty patients (36%) had evidence of improvement in neuroimaging, consisting of decrease in T2 signal abnormality +/- decrease in T1 gadolinium enhancement, on stable or reduced steroid doses. Progression-free survival at 6 months was 7.8% and median overall survival was 4.4 months. Median time to progression (TTP) for all patients was 2.3 months and was significantly longer for responders (5.4 months) versus nonresponders (1.9 months). Development of grade 2 or higher hyperlipidemia in the first two treatment cycles was associated with a higher percentage of radiographic response (71% v 31%; P = .04). Significant correlation was observed between radiographic improvement and high levels of phosphorylated p70s6 kinase in baseline tumor samples (P = .04). CONCLUSION Temsirolimus is well tolerated in recurrent GBM patients. Despite the effect of EIACs on temsirolimus metabolism, therapeutic levels were achieved. Radiographic improvement was observed in 36% of temsirolimus-treated patients, and was associated with significantly longer TTP. High levels of phosphorylated p70s6 kinase in baseline tumor samples appear to predict a patient population more likely to derive benefit from treatment. These findings should be validated in other studies of mTOR inhibitors.
The clinical management in familial adenomatous polyposis deserves continuous monitoring for thyroid carcinoma

Papillary thyroid carcinoma is an extraintestinal manifestation of patients with familial adenomatous polyposis, mainly occurring in young women. Recent publications highlight that familial adenomatous polyposis-associated papillary thyroid carcinoma represents a distinct type of follicular cell neoplasm histologically characterised by cribriform-morular aspects, the incidence of which has probably been underestimated so far. We report a case history of familial adenomatous polyposis-associated papillary thyroid carcinoma occurring in a 55-year-old man with Gardner syndrome, underscoring the importance of careful ultrasound screening examination of the thyroid gland in this condition.
Australian disability reform and political participation

The dynamics of disability social policy, political participation and communication rights are complex. Overview An epochal social policy reform in Australia is the National Disability Insurance Scheme (NDIS). Much is to unfold concerning the realities of what the NDIS will offer Australians with disabilities, and society at large, and to what extent the NDIS will deliver on its promise of being a transformational change. This paper engages with the complex dynamics of disability social policy, with a focus on political participation and its close relationship to communication rights. The right to political and public participation is a key article in the United Nations Convention on the Rights of Persons with Disabilities (article 29). Crucially, it interacts with article 21, which deals with freedom of expression and opinion, and access to information. From this vantage point, what does the unfolding case of the NDIS tell us about communication, social policy and political participation? How did—and does—communication evolve concerning NDIS? What kinds of voice and what types of listening does the NDIS afford for people with disabilities, in relation to the transformation of disability in Australia? How do new digital technologies and media cultures offer new relationships between communication and political participation? What are the implications of the NDIS for political participation for people with disabilities? Gerard Goggin and Dinesh Wadiwel’s paper was presented at the Reform and Rhetoric in Australian Social Policy Symposium which brought together researchers at The University of Sydney on 19 September 2014 to discuss how contemporary social policy is being talked about, designed and debated, and is published in the Australian Review of Public Affairs.
Programmed cell death in the regenerating deer antler

Antlers are the only mammalian appendages capable of epimorphic regeneration and thus provide a unique model for investigating the mechanisms that underlie mammalian regeneration. Antlers elongate by a modified endochondral ossification process while intramembranous ossification takes place concurrently around the antler shaft. In this study, sites of apoptosis in the growing antler tip were identified by TUNEL staining and related to cell proliferation, as determined by PCNA staining. Bcl‐2 and bax were identified by RT‐PCR and bax was also immunolocalized in tissue sections. The apoptotic index was high in perichondrium, undifferentiated mesenchymal cells and cellular periosteum but was low in skin. The proliferation index was high in mesenchyme, skin (specifically in hair follicles) and cellular periosteum; it was low in fibrous perichondrium and periosteum, and barely detectable in cartilage. Both bcl‐2 and bax were found to be more highly expressed in the perichondrium/mesenchyme and non‐mineralized cartilage than in skin and mineralized cartilage. Bax was immunolocalized in mesenchyme cells, chondroprogenitors, chondrocytes, osteoblasts, osteocytes and osteoclasts. In conclusion, this study shows that programmed cell death plays a necessary role in regenerating antlers, as it does during skeletal development, bone growth and bone remodelling. The high level of apoptosis and proliferation in mesenchymal progenitor cells confirms that this represents the antler ‘growth zone’. In fact, the percentage of TUNEL‐positive cells in the mesenchymal growth zone (up to 64%) is higher than that recorded in any other adult tissue. This extensive cell death probably reflects the phenomenal rate of morphogenesis and tissue remodelling that takes place in a growing antler. The local and/or systemic factors that control the balance between cell growth and apoptosis in antler tissues now need to be determined.
INTRAPOPULATIONAL VARIATION IN POLLEN‐MEDIATED GENE FLOW IN PLANTAGO LANCEOLATA L.

The extent of genetic variation in pollen‐mediated gene flow distance was measured for a population of the wind‐pollinated herb, Plantago lanceolata. Twenty‐nine genotypes were collected from a natural population, clonally replicated, and grown to reproductive maturity in a greenhouse. Relative gene flow distances were measured for each replicate and genotype in a wind tunnel. Approximately five percent of the total variation in gene flow distance was attributable to variation among genotypes. Most of the remaining variation was attributable to differences between the early part of the growing season, when most of the flowering occurs, and the remainder of the season, when flowering is sparse. The rankings of the genotypes' gene flow distances showed significant concordance between the early‐season measures and measures from later in the summer.
The epidemiology of eating disorders in Fyn County, Denmark, 1977–1986

The occurrence of anorexia nervosa and bulimia in Fyn County, Denmark is described. Incidence was estimated from national and local registers. The DSM‐III‐R criteria of one or both eating disorders were met by 104 patients. The incidence of anorexia nervosa for females 10 to 24 years of age was 11.0 per 100,000 per year. In the same population, the incidence of bulimia was 5.5 per 100,000 per year. Prevalence was estimated from questionnaires to and interviews with general practitioners. There were 193 cases; the prevalence of anorexia nervosa was estimated at 1:780 (patient years/total population years), and the prevalence of bulimia at 1:1480, in the high‐risk population: females 15–19 years of age. Sixty percent of the anorexia nervosa patients, but only 30% of the bulimia patients, were admitted to hospital; this is an important difference in regard to estimation of occurrence from registers.
Timing is everything: Anticipatory stress dynamics among cortisol and blood pressure reactivity and recovery in healthy adults

Psychological states of anticipation modulate biological stress responsivity. While researchers generally investigate how subjective distress corresponds to the magnitude of stress reactivity, physiological recovery after acute stressors must also be considered when investigating disease vulnerabilities. This study assessed whether anticipatory stress would correspond to stress reactivity and recovery of salivary cortisol and blood pressure levels in response to a well-validated psychosocial stressor. Thirty participants (63% female; mean ± SEM age 45.4 ± 2.12 years) were exposed to the Trier Social Stress Test (TSST) consisting of a public speech and mental arithmetic. Ten salivary cortisol samples and systolic and diastolic blood pressure recordings were collected at time points spanning 50 min before and up to 50 min after stress exposure. These data were transformed into parameters representing stress reactivity (area under the curve) and stress recovery (percent change). The Primary Appraisal Secondary Appraisal scale assessed anticipatory stress before exposure to the TSST. Our results revealed that increased anticipatory stress predicted increased stress reactivity for cortisol (p = 0.009) but not blood pressure. For stress recovery, increased anticipatory stress predicted greater decrements of cortisol concentration (p = 0.015) and blood pressure (p = 0.039), even when controlling for total systemic “output” by incorporating baseline activity. This efficient shutdown of stress responses would have otherwise been ignored by solely investigating reactive increases. These findings underscore the importance of measuring multiple dynamic parameters such as recovery when investigating physiological stress response patterns as a function of psychosocial factors.
Effect of ionic strength in immunocytochemical detection of the proliferation associated nuclear antigens p120, PCNA, and the protein reacting with Ki-67 antibody.

This study was aimed at revealing whether or not ionic interactions between the epitope of the antigen detected by Ki-67 antibody, or the proliferation-associated proteins PCNA or p120, and neighboring cellular constituents impede detectability of these antigens in HL-60 cells by indirect immunofluorescence assay. To this end, the ionic strength (NaCl concentration) of the solutions in which cells were suspended during their fixation with 0.5% paraformaldehyde was increased, to up to 1.65 M NaCl, to weaken the intra- and/or intermolecular ionic interactions during the process of crosslinking, and the cells were then immunostained. Fluorescence of cells reacting with Ki-67 antibody was maximally increased after their treatment with 1.15 M NaCl; the average increase was nearly 110% above the level seen with the standard methodology utilizing 0.15 M NaCl. The increase was greater for cells in the G1 phase of the cell cycle compared to cells in S or G2. Fluorescence of cells stained with the PCNA antibody was maximally enhanced after cell treatment with 0.65 M NaCl. The enhancement, however, varied depending on the source of the antibody; it was nearly 200% in the case of the antibody provided by Boehringer and over 100% by DAKO. Detection of the nucleolar antigen p120 was not significantly affected by 0.65-1.65 M NaCl. The data indicate that ionic interactions between cellular constituents indeed play a role in masking the epitope of PCNA and the antigen detected by Ki-67. (ABSTRACT TRUNCATED AT 250 WORDS)
Environmental manipulations early in development alter seizure activity, Ih and HCN1 protein expression later in life

Although absence epilepsy has a genetic origin, evidence from an animal model (Wistar Albino Glaxo/Rijswijk; WAG/Rij) suggests that seizures are sensitive to environmental manipulations. Here, we show that manipulations of the early rearing environment (neonatal handling, maternal deprivation) of WAG/Rij rats leads to a pronounced decrease in seizure activity later in life. Recent observations link seizure activity in WAG/Rij rats to the hyperpolarization‐activated cation current (Ih) in the somatosensory cortex, the site of seizure generation. Therefore, we investigated whether the alterations in seizure activity between rats reared differently might be correlated with changes in Ih and its channel subunits hyperpolarization‐activated cation channel HCN1, 2 and 4. Whole‐cell recordings from layer 5 pyramidal neurons, in situ hybridization and Western blot of the somatosensory cortex revealed an increase in Ih and HCN1 in neonatal handled and maternal deprived, compared to control rats. The increase was specific to HCN1 protein expression and did not involve HCN2/4 protein expression, or mRNA expression of any of the subunits (HCN1, 2, 4). Our findings provide the first evidence that relatively mild changes in the neonatal environment have a long‐term impact of absence seizures, Ih and HCN1, and suggest that an increase of Ih and HCN1 is associated with absence seizure reduction. Our findings shed new light on the role of Ih and HCN in brain functioning and development and demonstrate that genetically determined absence seizures are quite sensitive for early interventions.
High age-adjusted prevalence of Parkinson’s disease among Inuits in Greenland

Abstract—The prevalence of PD among Inuits in Greenland has not been determined. The authors found 40 patients with PD at the prevalence date January 1, 2000. The crude prevalence of PD was estimated to be 81.0 per 100.000 inhabitants born in Greenland. However, owing to the low proportion of 50+ year old Inuits (16.5 vs 33.5% in Denmark) the age-adjusted prevalence was much higher—187.5 per 100,000 persons.
English-only Instruction in Post-secondary Education in Taiwan: Voices from Students

The internationalization of higher education in Taiwan has become a trend since Taiwan entered the World Trade Organization (WTO). One of the most popular internationalizing mechanisms for Taiwan is to provide English-taught courses in postsecondary education. Despite its proliferation, we rarely have empirical studies on its effectiveness, which 15 particularly important since Vinke et al. (1998) found that the effects of using English as the only medium of teaching to facilitate one' s language abilities and international understanding were not totally positive. This paper thus aims to report student voices regarding English-Only instruction in one department in a comprehensive, private university in Taiwan. Ten student interviews were conducted. Data were analyzed by Carspecken's (1996) reconstructive analysis. The results showed delicate complexity between positive and negative learning effects. The students perceived English improvement in terms of listening, vocabulary and confidence, while they expressed worries about a loss in their acquisition of professional knowledge. In addition to teachers' clarity and expressiveness, students' language ego, intrinsic motivation, proficiency levels and time for adjustment also account for learning effectiveness. Although the results are inconclusive, the complicated factors emerging from student data, I believe, function as a preliminary step for an in-depth understanding of the effectiveness of English-only instruction and the anticipated future internationalization of higher education in Taiwan.
Repeat adverse drug reactions causing hospitalization in older Australians: a population-based longitudinal study 1980-2003.

AIM To examine trends in the rate of repeat adverse drug reactions (ADRs) causing hospitalization in older Australians and to identify the most common ADRs and drugs most often implicated in repeat and first-time ADRs. METHODS Analysis of routinely collected hospital record administrative data, with International Classification of Diseases external cause codes for ADRs extracted from the Western Australia (WA) Hospital Morbidity Data System and WA Death Register, for people aged > or =60 years in 1980-2003. RESULTS A total of 37 296 people aged > or =60 years with an ADR-related hospitalization were identified. Among them, 6853 (18.4%) patients had 10 212 repeat ADRs. Repeat ADRs consistently increased from 1980 and reached 30.3% of all ADRs by 2003. The mean time interval declined with each successive repeat ADR (810, 606 and 299 days for the first, second and higher ranked repeat episodes, respectively). The most common repeat ADRs were nausea/vomiting (8.0%), haemorrhage due to anticoagulants (5.5%), drug-induced osteoporosis (4.8%) and poisoning by cardiovascular agents (3.9%). The drugs most often involved in repeat ADRs were cardiovascular agents (15.6%), antineoplastic drugs (11.0%), corticoids (10.1%), anticoagulants (8.6%), antirheumatics/nonsteroidal anti-inflammatory drugs (5.1%) and opioids (4.9%). The trends of anticoagulants and antineoplastic drugs implicated in repeat ADRs were still rising at the end of the study. The specific drug classes involved in repeat ADRs differed in relative importance from first-time ADRs. CONCLUSIONS Repeat ADR-related hospitalizations have consistently increased in elderly Australians from 1980 to 2003. Strategies to ensure the safer use of medicines, in particular anticoagulants, in this population are warranted.
The Composition of Government Spending and Economic Growth in Developing Countries: The Case of Latin America

This paper aims to identify the effects of the two economic components of government spending, namely, capital and current spending, on the per capita economic growth rate in a set of Latin American countries over the period 1975-2000. Within the neoclassical framework (Solow, 1956; Swan, 1956), government spending, and public policy in general, has no role in determining the long-run economic growth rate, since this is determined by the exogenous population growth and technological progress rates. On the other hand, in some endogenous growth models developed mainly since the early 1990s, such as Easterly (1990), Barro (1990), Barro and Sala-i-Martin (1992, and 2004), Cashin (1995), Bajo-Rubio (2001), and Milbourne et al. (2003), fiscal policy affects the long-term growth rate through decisions on either taxes or expenditures.The empirical literature tends to reject the predictions of the neoclassical model, in the sense that according to this model, fiscal policy cannot affect growth in the long term. However, results are far from conclusive and it seems they depend on various aspects such as methods or techniques used, assumptions, country or set of countries analyzed, and so on. As long as theoretical models about the influence of public spending on growth is concerned, some of them such as Barro (1990), Cashin (1995), Bajo-Rubio (2000), and Milbourne et al. (2003) predict that a positive effect is expected to be found in countries where the size of government is smaller than a certain threshold, and a negative one in countries where the size of government is bigger than that. Therefore, since generally speaking, with few exceptions, one finds very large public sectors only in developed countries (DCs), studies evaluating the impact of public expenditure on growth should analyze DCs and less developed countries (LDCs) separately. In line with recent growth literature, the study uses a generalized method of moments as suggested by Arellano and Bond (1991) in order to obtain consistent and efficient estimates for a dynamic model, such as an economic growth model.This paper’s findings suggest that neither government capital nor current expenditures have any impact on the per capita economic growth rate. The positive effect of government capital spending reported in some literature was not found here. Statistically insignificant estimated effects of these kinds of spending could be due to inefficiency. Perhaps they are vulnerable to rent seeking. In addition, inefficiency of government spending has widely been associated in the literature with poor governance and corruption, which are, typically, some characteristics of developing countries.
Genetic susceptibility to ulcerative colitis in the Chinese Han ethnic population: association with TNF polymorphisms.

BACKGROUND Tumor necrosis factor alpha (TNFalpha) is an important proinflammatory cytokine that has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Recent studies have evaluated the role of TNF promoter polymorphisms in IBD, whereas the data are inconsistent. Trans-racial mapping in an ethnically distinct but homogenous population may help clarify these associations. We investigate the association between TNF promoter polymorphisms and susceptibility to ulcerative colitis (UC) in the Chinese Han ethnic population. METHODS We studied 110 unrelated UC patients and 292 healthy controls from Zhejiang Province, China. Genotyping for 6 common TNF promoter polymorphisms (TNF -1031T/C, -863C/A, -857C/T, -380G/A, -308G/A, -238G/A) was carried out by polymerase chain reaction sequence-specific primers (PCR-SSP). RESULTS TNF -308A was associated with disease (allele frequency patients 14.6% vs controls 8.9%, P = 0.02). TNF -857T was increased in patients but without statistical significance (allele frequency 17.3% vs 12.2%, P = 0.06). Haplotype analysis revealed 6 haplotypes including two (H5 and H3), which contained TNF -308A. H5 was associated with disease (haplotype frequency patients -12.3% vs controls 7.5%, P = 0.03). Of note the rare haplotype H3 has not previously been identified in Caucasian populations. Homozygosity for the haplotype H4 comprising the common alleles at each TNF promoter single-nucleotide polymorphism (SNP) was negatively associated with disease (patients vs controls 24.5% vs 34.9%, P < 0.05). CONCLUSIONS We report the association with TNF -308A polymorphisms in Chinese patients with ulcerative colitis. The functional study in Chinese Han ethnic population is now required.
Hearing Impairment and Tinnitus Pitch in Patients With Unilateral Tinnitus: Comparison of Sudden Hearing Loss and Chronic Tinnitus

Objectives The objectives were to analyze the results of pitch‐matching and loudness‐balance testing in patients with unilateral tinnitus and to evaluate the relationship between audiological findings based on the tinnitus‐affected and tinnitus‐unaffected threshold differences and tinnitus pitch by using linear interpolation methods. In addition, the effects of the duration of the tinnitus on this relationship were investigated. Sudden sensorineural hearing loss with tinnitus was selected for the “acute tinnitus” group, and unilateral tinnitus with unknown disease and a duration of more than 3 months was selected for the “chronic tinnitus” group.