Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized Phase II Trial of Erlotinib Beyond Progression in Advanced Erlotinib-Responsive Non-Small Cell Lung Cancer.

BACKGROUND Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is clearly beneficial in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance develops uniformly and the benefit of continuation of EGFR TKI therapy beyond progression remains unclear. MATERIALS AND METHODS This was a randomized phase II study of chemotherapy (arm A: pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) (arm B) in patients with progressive NSCLC following clinical benefit from erlotinib. In arm B, chemotherapy was given with erlotinib at an oral daily dose of 150 mg on days 2-19 of each cycle to minimize negative pharmacodynamic interactions. The primary endpoint was that continuation of erlotinib in this patient population could extend progression-free survival (PFS) by 50%. RESULTS A total of 46 patients were randomized (arm A: 24; arm B: 22). Patient characteristics were well balanced except there were more female patients in arm A (p = .075). The median PFS of patients in arm A was 5.5 months and for those in arm B, 4.4 months (p = .699). The response rates were 13% and 16% in arms A and B, respectively (p = .79). EGFR status data were available for 39 of the 46 patients and no significant difference in PFS was seen for continuing ERL beyond progression in mutation-positive patients. Substantially more toxicity was seen in arm B than arm A. CONCLUSION There was added toxicity but no benefit with the continuation of ERL beyond progression along with chemotherapy as compared with chemotherapy alone. IMPLICATIONS FOR PRACTICE The benefits of continuing erlotinib upon progression alongside conventional chemotherapy are unclear. This randomized phase II study, initiated prior to the establishment of routine epidermal growth factor receptor (EGFR) mutation testing, addressed this clinically relevant issue through randomizing patients with prior clinical benefit from erlotinib (thereby enriching for EGFR-mutated tumors) upon progression in the second- or third-line setting to conventional chemotherapy (single-agent pemetrexed or docetaxel) with or without continued erlotinib. The results showed no benefit to continuing erlotinib beyond progression, while significantly more side effects were noted in the combination arm. Along with other recently presented study findings, these results argue against the routine practice of continuing erlotinib in this setting.
Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation

Mastocytosis is a rare neoplastic disease characterized by a pathologic accumulation of tissue mast cells (MCs). Mastocytosis is often associated with a somatic point mutation in the Kit protooncogene leading to an Asp/Val substitution at position 816 in the kinase domain of this receptor. The contribution of this mutation to mastocytosis development remains unclear. In addition, the clinical heterogeneity presented by mastocytosis patients carrying the same mutation is unexplained. We report that a disease with striking similarities to human mastocytosis develops spontaneously in transgenic mice expressing the human Asp816Val mutant Kit protooncogene specifically in MCs. This disease is characterized by clinical signs ranging from a localized and indolent MC hyperplasia to an invasive MC tumor. In addition, bone marrow–derived MCs from transgenic animals can be maintained in culture for >24 mo and acquire growth factor independency for proliferation. These results demonstrate a causal link in vivo between the Asp816Val Kit mutation and MC neoplasia and suggest a basis for the clinical heterogeneity of human mastocytosis.
Age differences in recall and recognition

An experiment is reported in which young and elderly adults performed cued-recall and recognition tests while carrying out a choice reaction-time task. An analysis of covariance, with recognition performance as the covariate, showed a reliable age decrement in recall. It was therefore concluded that older people perform more poorly on recall tasks than they do on recognition tasks. Performance on the secondary (reaction time) task showed that recall was associated with greater resource "costs" than was recognition and that this effect was amplified by increasing age. The results are in line with the suggestion that recall requires more processing resources than does recognition and that such resources are depleted as people grow older. The literature on age differences in human memory includes a large number of studies comparing the performance of young and old adults on tests of recall and recognition memory. The results of these studies have consistently shown an age decrement in recall performance (see Botwinick, 1978; Burke &
NAEP and No Child Left Behind: Technical Challenges and Practical Solutions

The National Assessment of Educational Progress (NAEP) is the only nationally representative and continuing assessment of what U.S. students know and can do in various subject areas. The No Child Left Behind Act of 2001 requires that all U.S. states, jurisdictions, and territories submit plans to the Secretary of Education that demonstrate that the state has adopted challenging academic content and student achievement standards. As part of that plan, states and school districts that receive Title I funds must participate in NAEP assessments in reading and math at grades 4 and 8 every two years. The purpose of NAEP has always been to survey what students know and can do and to monitor changes over time. Now, NAEP has a new role, to act as a serious discussion tool in evaluating results of state assessments and in providing a common base for comparison between states. This role brings new challenges and opportunities for the NAEP program.
How far are we in understanding the cause of Parkinson's disease?

the writer will repine at no censure which the precipitate publication of mere conjectural suggestions may incur: but shall think himself fully rewarded by having excited the attention of those, who may point out the most appropriate means of relieving a tedious and most distressing malady. James Parkinson' It is almost 180 years since James Parkinson described his series of patients with what is now known as Parkinson's disease. His own astute clinical observations were unable to discern any obvious aetiology. "On the subject indeed of remote causes, no satisfactory account has yet been obtained from any of the sufferers. "' He noted an indulgence in alcohol, lying on damp ground, and the possibility of trauma. He also reported the occupations of three of his patients; one was a gardener, another a sailor, and the third a magistrate. Even in 1817, the disease affected a broad social range of society. We have made some progress in elucidating the cause of Parkinson's disease over this period but this has been limited. For instance, the role of trauma in the aetiology of Parkinson's disease remains uncertain and disputed.2 4 Epidemiological research has steadily increased, particularly over the past 10 years, and more research has been directed towards analytical rather than just descriptive studies. More recently, work in the area of genetic epidemiology5 has begun and researchers are now focusing on both molecular and environmental risk factors. This review interprets the existing evidence and provides a personal view on what we definitively know about the epidemiology of Parkinson's disease, what remains speculative, and what questions remain to be answered.
Self optimizing ABS control algorithm with application

A self optimizing control algorithm is applied to the ABS control problem where the algorithm accomplishes to maximize friction potential of the tires during braking in unknown road conditions. Simulation studies are conducted to show effectiveness of the controller. The algorithm is also tested in an experimental setup. In order to control a real electromechanical braking system, necessary observers are designed and integrated with the algorithm. Experimental study shows the performance of the control algorithm.
Playing with Ideas and Games in Early Mathematics

This article investigates learning in an out-of-school informal computer club. Particularly, it sought to elucidate information about mathematical learning and understandings that were displayed when children played and interacted in computer-based contexts. It was also concerned with the social processes inherent to game playing and the design features of computer games which appealed to children. The data revealed that mathematical understandings can be promoted and practised in computer games and that the structure and design of the game determined the amount and quality of the interactions that children engage in. Children of all ages preferred games that had a design element and catered for different levels of participation. Additionally, they liked games that had a narrative and adventure context in which activities were situated with some purpose.
Chinese a Nti鄄 Cancer a Ssociation

Insulin鄄 like growth factor鄄 binding proteins (IGFBPs) are critical regulators of the mitogenic activity of insulin鄄 like growth factors (IGFs). IGFBP5, one of these IGFBPs, has special structural features, including a nuclear transport domain, heparin鄄 binding motif, and IGF/extracellular matrix/acid鄄 labile subunit鄄 binding sites. Furthermore, IGFBP5 has several functional effects on carcinogenesis and even normal cell processes, such as cell growth, death, motility, and tissue remodeling. These biological effects are sometimes related with IGF (IGF鄄 dependent effects) and sometimes not (IGF鄄 independent effects). The functional role of IGFBP5 is most likely determined in a cell鄄 type and tissue鄄 type specific manner but also depends on cell context, especially in terms of the diversity of interacting proteins and the potential for nuclear localization. Clinical findings show that IGFBP5 has the potential to be a useful clinical biomarker for predicting response to therapy and clinical outcome of cancer patients. In this review, we summarize the functional diversity and clinical importance of IGFBP5 in different types of cancers.
Sex differences in perceived competence

Consideration of the literature on self-concept indicates the necessity for a multidimensional model of self-perceived competence. The Perceived Competence Scale for Children (PCSC) was completed by 102 boys and 88 girls aged 11 years. Girls were significantly lower on physical and general competence than boys. Intercorrelations of the PCSC for girls demonstrate significantly stronger associations between physical and cognitive competence, and physical and general competence, than for boys. It is concluded that combining data for boys and girls, as if their self-construals of competence were similar, does not represent a picture of perceived competence that is necessarily true for either sex.
The Role of Ethnic Real Estate Agents in the Residential Relocation Process: A Case Study of Portuguese Homebuyers in Suburban Toronto.

This paper examines the search behavior of a sample of Portuguese and Canadian-born homebuyers in suburban Toronto, Canada. Attention is focused on the extent to which Portuguese homebuyers rely upon real estate agents from the same ethnic background and how this source can influence the homebuyer's housing search and ultimate choice of a residence. Data were obtained from a questionnaire survey that was administered to a sample of 110 Portuguese and 90 Canadian-born recent homebuyers in the city of Mississauga, a western suburb of Toronto. All were nonresidents of Mississauga at the time of purchasing the house. The evidence indicates that Portuguese homebuyers differ significantly from the Canadian-born in their housing search by relying more extensively on ethnic sources of information, particularly real estate agents from the same ethnic background. However, almost equal numbers of Portuguese purchased houses in Portuguese and non-Portuguese neighborhoods in Mississauga. In this respect, the evidence .
Generalised improvement in speech production for a subject with reproduction conduction aphasia

Background: Reproduction conduction aphasia is a disorder of phonological production characterised by phonological errors occurring particularly with longer words in all tasks requiring spoken output. There have been few previous studies of therapy for subjects with this disorder. Aims: The study investigates the effects of a treatment procedure involving the detection and correction of the errors in speech production with a single subject, MB. We also seek to establish the nature of MB's underlying deficit, and show how it changes as a result of treatment. Methods & Procedures: Treatment effects were investigated in a single case study using multiple baselines over tasks, materials, and time. An in-depth cognitive neuropsychological case study was used to investigate the nature of MB's speech production deficit. Outcomes & Results: MB had impaired naming, repetition, and oral reading particularly with longer words, but good word comprehension. Her errors were primarily phonological, with many repeated attempts (“conduite d'approche”). Production of non-words was less accurate than real words. The treatment improved production in all modalities and across a variety of tasks (including non-word reading). Further analysis of assessment results suggested that MB's impairment was at the level of phonological encoding and that therapy had improved phoneme production across all word positions. Conclusions: Treatment was successful and generalised across items and to connected speech. MB's deficit could be characterised as a difficulty in the process of phoneme retrieval, and this improved as a result of the treatment.
Prosthesis-Patient Mismatch Predicts Structural Valve Degeneration in Bioprosthetic Heart Valves

Background— Prosthesis-patient mismatch (P-PtM) after aortic valve replacement results in disturbed valve performance associated with increased pressure gradients. However, it is unknown whether this can be related to future structural valve deterioration (SVD) of the bioprosthesis. Methods and Results— In 564 patients (mean age, 74±5 years) receiving an aortic valve bioprosthesis, clinical follow-up (median, 6.1 years; maximum, 16.4 years) was analyzed including echocardiography. SVD was diagnosed in 40 patients (7%) as substantially increased stenosis (n=24) or regurgitation (n=16) of the operated valve over time. When patients with P-PtM (effective orifice area index <0.85 cm2/m2; n=285) developed SVD, it was preferentially of the stenosis type, whereas when patients without P-PtM (n=279) developed SVD, the majority was of the incompetence type (P<0.05). Multivariable analysis including patient- and valve-related variables revealed that P-PtM and label size ≤21 were independent predictors of SVD (P=0.04 and P=0.02, respectively). A nonparametric Turnbull estimate analysis showed that SVD is virtually nonexistent for up to 9 years in patients without P-PtM. Thereafter, SVD starts to occur and is mainly of the incompetence-type SVD (79% of cases). In patients with P-PtM, SVD starts to occur after 2 to 3 years after implantation and is mainly of the stenosis-type SVD (81% of cases). Conclusions— These data suggest that stenosis-type SVD is an early, P-PtM–related, and thus preventable phenomenon. Incompetence-type SVD is a time-dependent, nonspecific wear damage to bioprosthetic valves, which is not related to P-PtM.
Practice and policy in the UK with children and young people who display harmful sexual behaviours: an analysis and critical review

Abstract This article considers the trajectory and effectiveness of policy, procedures and practice in the UK since the early 1990s in responding to young people who display problematic and harmful sexual behaviours. It draws on data from three publications in which research, policy and practice in the last 20 years have been reviewed. Key themes raised by Masson and Hackett are revisited including: denial and minimisation; terminology and categorisation; similarities with other young offenders; the child protection and youth justice systems; and assessment and interventions. The authors find that there is improvement in recognition of, and practice in response to, this group of young people, but good practice standards are inconsistently applied. With devolution of political powers, Scotland and Northern Ireland are now embarking on a more strategic response than England. The absence of a public debate and prioritising of primary prevention of child sexual abuse is noted.
Sexual Hypnotherapy for Couples and Family Counselors

This article presents the utilization of Ericksonian hypnotic techniques in conjunction with cognitive behavioral techniques collectively labeled the New Hypnosis, as they apply to the treatment of male and female sexual dysfunction within a counseling setting. The basic principles of the New Hypnosis (as they apply to sexual dysfunction) include processing of internal states of perceived realities, in vitro reexperiencing of the sexual problem, inward directedness of the client by the counselor via careful observation and feedback of the client’s/couple’s psychosematics and somatopsychic expressions, and the presence of both members of the couple in the session whenever possible. Subjective biofeedback, activation of personality parts, and mental rehearsal are techniques reviewed as they apply to sexual identity, orientation, preference, role, and functioning. Specific techniques to improve functioning throughout the five stages of sexual response (desire, arousal, foreplay, orgasm, and processing) are presented. The New Hypnosis is an effective means of helping clients develop new insights into their sexual functioning and overcome debilitating or limiting sexual dysfunctions.
Invisible and special: young women’s experiences as undergraduate mathematics students

This paper reports on young women students’ participation in their undergraduate mathematics degree programme: their gendered trajectory is characterized in terms of their being both ‘invisible’ in the dominant university mathematics community and yet ‘special’ in their self‐conception. It draws on data collected from a three‐year longitudinal project investigating students’ experiences of undergraduate mathematics at two comparable traditional universities in England. Specifically, students’ narratives are interpreted as providing insights into their defensive investments in their particular ways of participating. An interpretive feminist perspective is used to claim that these young women are involved in the ongoing redefining of the gendering of participation in mathematics, and conveys how they manage to choose mathematics, and achieve in university mathematics, whilst in many respects adhering to everyday views of femininity. Leitmotif No one could see [the witch] Serafina from where she was; but if she wanted to see any more, she would have to leave her hiding place. …There was one thing she could do; she was reluctant because it was desperately risky, and it would leave her exhausted; but it seemed there was no choice. It was a kind of magic she could work to make herself unseen. True invisibility was impossible, of course: this was mental magic, a kind of fiercely held modesty that could make the spell worker not invisible but simply unnoticed. Holding it with the right degree of intensity, she could pass through a crowded room, or walk beside a solitary traveller, without being seen. (Pullman, 1998, p. 35)
Geometry eigenvalues and the scalar product from recoupling theory in loop quantum gravity.

We summarize the basics of the loop representation of quantum gravity and describe the main aspects of the formalism, including its latest developments, in a reorganized and consistent form. Recoupling theory, in its graphical tangle-theoretic Temperley-Lieb formulation, provides a powerful calculation tool in this context. We describe its application to the loop representation in detail. Using recoupling theory, we derive general expressions for the spectrum of the quantum area and the quantum volume operators. We compute several volume eigenvalues explicitly. We introduce a scalar product with respect to which area and volume are symmetric operators, and (the trivalent expansions of) the spin network states are orthonormal.
A long-term siRNA strategy regulates fibronectin overexpression and improves vascular lesions in retinas of diabetic rats

Purpose A sustained gene modulatory strategy is necessary for regulating abnormal gene expression in diabetic retinopathy, a long-term complication. We investigated the efficacy of a small interference RNA (siRNA) strategy in mediating the long-term downregulatory effect of fibronectin (FN) overexpression in vivo. Methods Streptozotocin-induced diabetic rats were intravitreally injected with 3 µM of FN-siRNA at six week intervals over a period of 4.5 months. Retinal FN protein expression, vascular basement membrane (BM) thickness, and retinal vascular cell loss were assessed by western blot, electron microscopy, and retinal trypsin digest, respectively. Results Retinal FN expression and BM thickness were significantly increased in diabetic rat retinas compared to those in non-diabetic control rats (188±14.2% of control versus 100±7.4% of control, p<0.002; 72.5±5.0 nm versus 51.5±4.8 nm, p<0.001, respectively). FN-siRNA treatment reduced FN overexpression and BM thickening (145±19.9% of control and 56.4±2.8 nm, respectively) and significantly reduced the number of acellular capillaries (35%) and pericyte loss (55%) compared to those of untreated diabetic eyes. Conclusions These findings suggest that BM thickening is an important target for preventing vascular cell loss in a diabetic retina, and that the siRNA approach could be useful for long-term gene modulation in diabetic retinopathy.
Local and Systemic Immune Mechanisms Underlying the Anti-Colitis Effects of the Dairy Bacterium Lactobacillus delbrueckii

Several probiotic bacteria have been proposed for treatment or prevention of inflammatory bowel diseases (IBD), showing a protective effect in animal models of experimental colitis and for some of them also in human clinical trials. While most of these probiotic bacteria are isolated from the digestive tract, we recently reported that a Lactobacillus strain isolated from cheese, L. delbrueckii subsp. lactis CNRZ327 (Lb CNRZ327), also possesses anti-inflammatory effects in vitro and in vivo, demonstrating that common dairy bacteria may be useful in the treatment or prevention of IBD. Here, we studied the mechanisms underlying the protective effects of Lb CNRZ327 in vivo, in a mouse dextran sodium sulfate (DSS) colitis model. During colitis, Lb CNRZ327 modulated the production of TGF-β, IL-6, and IL-12 in colonic tissue and of TGF-β and IL-6 in the spleen, and caused an expansion of CD4+Foxp3+ regulatory T cells in the cecal lymph nodes. Moreover, a strong tendency to CD4+Foxp3+ expansion was also observed in the spleen. The results of this study for the first time show that orally administered dairy lactobacilli can not only modulate mucosal but also systemic immune responses and constitute an effective treatment of IBD.
Identification of Novel ARF Binding Proteins by Two-Hybrid Screening

The ARF tumor suppressor protects us against cancer through protein-protein interactionsin partially defined p53-dependent and p53-independent pathways. We performed a two-hybridscreen using ARF as bait and present the identification of several new ARF partners that mayregulate its growth inhibitory signaling. The potential physiological roles of these novel ARFbinding proteins in regulating ARF signaling are discussed.