Art for improving skills in medical education: the validation of a scale for measuring the Visual Thinking Strategies method.

BACKGROUND: The skills needed in the medical and nursing field are considered both for the cognitive and the personal and interpersonal aspects. There are many studies that suggest using artistic practices and pedagogical methods such as Visual Thinking Strategies (VTS) or Artful Thinking in the medical education. The main aim of this research is to validate a grid to evaluate impact of art activities for improving skills in medical education sector. METHODS: The VTSkill grid was created by research group of Sapienza University, selecting the relevant dimension on the basis of literature analysis. To evaluate the validity and reliability, the grid was used in a quasi-experimental study involving the pediatric ward personnel, the nursing and medicine course students of Sapienza University of Rome. This analytic rubric was used to evaluate the written assessment form, composed by open-ended basic question related to the VTS method, administered in association with two images, a work of art and a clinical image. The Number of responders of the validation study was 105. RESULTS: Although obtained from a small sample, both construct validity and reliability analysis showed coherent and statistically significant results. On one hand, the construct validity results showed a relationship path consistent with the hypothesised one derived from previous literature, with relevant p-values (n = 78). On the other hand, the VTSkill reliability was first analysed through the inter-rater evaluation data. This reliability coefficient showed a high degree of convergence of judgments between different evaluators on both image data (n = 55), with statistically significant values ranging from good (r = .77) up to excellent for objectively observable items (r = 1). Similarly, the test-retest reliability coefficients calculated for both clinical and artwork image data resulted statistically significant (n = 95), although ranging from weak to adequate entity (up to r = .77). CONCLUSIONS: Taking into account the high degree of coherence and the stability of measurement of VTSkill in combination with its consistent construct validity, this study suggest the opportunity to implement this measurement tool to research the effect of VTS protocol in future investigations on the field. Therefore, the results of this study will constitute the basis to collect further evidences on how arts-based learning methods can contribute in medical education to improve skills suitable to the health professionals.

Proposed design and optimization of a higher harmonic cavity for ALS-U.

Higher harmonic cavities (HHCs), also known as Landau cavities, have been proposed to increase the beam lifetime and Landau damping by lengthening the bunch and increasing the synchrotron tune spread. Here, we present an optimized 1.5 GHz normal conducting HHC design for the Advanced Light Source Upgrade project at Lawrence Berkeley National Lab with a superconducting-like geometry for lower R/Q. The optimization goal is to reach the required shunt impedance while maintaining a relatively high Q value of the cavities. A multi-objective genetic algorithm (MOGA)-based optimization process is applied to optimize the radio frequency (RF) design. This study serves as an example of how a genetic algorithm can be used to optimize RF cavities. Detailed exploration and characterization of the MOGA-based RF cavity optimization have been demonstrated from the aspects of minimizing the coupled bunch instabilities and analyzing the higher-order modes and the corresponding impedance of the HHC.

Hyper-activation of Aurora kinase a-polo-like kinase 1-FOXM1 axis promotes chronic myeloid leukemia resistance to tyrosine kinase inhibitors.

BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the constitutive tyrosine kinase (TK) activity of the BCR-ABL1 fusion protein. Accordingly, TK inhibitors have drastically changed the disease prognosis. However, persistence of the transformed hematopoiesis even in patients who achieved a complete response to TK inhibitors and the disease relapse upon therapy discontinuation represent a major obstacle to CML cure. METHODS: Thiostrepton, Danusertib and Volasertib were used to investigate the effects of FOXM1, AKA and Plk1 inhibition in K562-S and K562-R cells. Apoptotic cell death was quantified by annexin V/propidium iodide staining and flow cytometry. Quantitative reverse transcription (RT)-PCR was used to assess BCR-ABL1, FOXM1, PLK1 and AURKA expression. Protein expression and activation was assessed by Western Blotting (WB). Clonogenic assay were performed to confirm K562-R resistance to Imatinib and to evaluate cells sensitivity to the different drugs. RESULTS: Here we proved that BCR-ABL1 TK-dependent hyper-activation of Aurora kinase A (AURKA)-Polo-like kinase 1 (PLK1)-FOXM1 axis is associated with the outcome of Imatinib (IM) resistance in an experimental model (K562 cell line) and bone marrow hematopoietic cells. Notably, such a biomolecular trait was detected in the putative leukemic stem cell (LSC) compartment characterized by a CD34+ phenotype. Constitutive phosphorylation of FOXM1 associated with BCR-ABL1 TK lets FOXM1 binding with ß-catenin enables ß-catenin nuclear import and recruitment to T cell factor/lymphoid enhancer-binding factor (TCF/LEF) transcription complex, hence supporting leukemic cell proliferation and survival. Lastly, the inhibition of single components of AURKA-PLK1-FOXM1 axis in response to specific drugs raises the expression of growth factor/DNA damage-inducible gene a (GADD45a), a strong inhibitor of AURKA and, as so, a critical component whose induction may mediate the eradication of leukemic clone. CONCLUSIONS: Our conclusion is that AURKA, PLK1 and FOXM1 inhibition may be considered as a promising therapeutic approach to cure CML.

TNFα deficiency results in increased IL-1ß in an early onset of spontaneous murine colitis.

Inflammatory bowel disease (Crohn's disease (CD) and ulcerative colitis (UC)) is a multifactorial disease resulting from immune dysregulation in the gut. The underlying colitis is characterized by high levels of inflammatory cytokines, including TNFα. Biological intervention for IBD patients using anti-TNFα antibodies is often an effective therapeutic solution. However, TNFα neutralization fails to induce remission in a subgroup of IBD patients, primarily in UC patients. There is a dearth of suitable animal models representing TNFα non-responders. Here we have combined one of the best UC models currently available, namely Winnie and the TNFαKO mouse to generate a TNFα-deficient Winnie to study early onset colitis. The induced TNFα deficiency with underlying colitis does not influence general health (viability and body weight) or clinical parameters (colon weight, colon length and histological colitis) when compared with the Winnie genotype alone. The molecular characterization resulted in identification of Il1ß as the major elevated cytokine during early phases of colitis. Further, in vitro functional assay using bone marrow-derived dendritic cells confirmed IL-1ß as the major cytokine released in the absence of TNFα. This study has generated a successful model of colitis that remains TNFα non-responsive and has demonstrated that IL-1ß expression is a major pathway for the progression of colitis in this system. These data also suggest that IL-1ß can be a potential target for clinical intervention of UC patients who fail to respond to TNFα neutralization.

Oropharyngeal squamous cell carcinoma and HPV. Systematic review on overall management.

INTRODUCTION: Oral human papillomavirus infection amplifies the risk for oropharyngeal cancer. Human papillomavirus-associated cancers in otorhinolaryngology have typical characteristics. PATIENTS AND METHODS: To improve understanding of management, therapy and prognosis of patients with oropharyngeal human papillomavirus-associated cancers a systematic review of the literature was reported. Medline, The Cochrane Library, Embase and Scielo electronic databases were searched. The search included published articles up to December 2006. A wide search strategy was employed in order to avoid publication biases and to assess studies in which the main aspects concerning oropharyngeal squamous cell carcinoma and human papillomavirus management are analyzed. RESULTS: A total of 120 articles were identified, of which 16 matched the inclusion criteria. DISCUSSION: Patients with human papillomavirus-associated oropharyngeal cancers have distinctive risk factors such as a high number of sex partners. They are typically younger, nonusers of tobacco and alcohol and have a better prognosis.

Supramolecular assembly of a thermoresponsive steroidal surfactant with an oppositely charged thermoresponsive block copolymer.

Supramolecular rearrangements are crucial in determining the response of stimuli sensitive soft matter systems such as those formed by mixtures of oppositely charged amphiphiles. Here mixtures of this kind were prepared by mixing the cationic block copolymer pAMPTMA30-b-pNIPAAM120 and an anionic surfactant obtained by the modification of the bile salt sodium cholate. As pure components, the two compounds presented a thermoresponsive self-assembly at around 30-35 °C; a micelle formation in the case of the copolymer and a transition from fibers to tubes in the case of the bile salt derivative. When both were present in the same solution they associated into mixed aggregates that showed complex thermoresponsive features. At room temperature, the core of the aggregate was comprised of a supramolecular twisted ribbon of the bile salt derivative. The block copolymers were anchored on the surface of this ribbon through electrostatic interactions between their charged blocks and the oppositely charged heads of the bile salt molecules. The whole structure was stabilized by a corona of the uncharged blocks that protruded into the surrounding solvent. By increasing the temperature to 30-34 °C the mixed aggregates transformed into rods with smooth edges that associated into bundles and clusters, which in turn induced clouding of the solution. Circular dichroism allowed us to follow progressive rearrangements of the supramolecular organization within the complex, occurring in the range of temperature of 20-70 °C.

RAPID: a routine assurance pipeline for imaging of diffusion.

Despite the widespread adoption of diffusion MRI techniques, there is still no consensus on a comprehensive quality assurance routine specific for diffusion acquisitions. We propose here a routine assurance pipeline for imaging of diffusion. The routine simply comprises diffusion-weighted acquisitions on a phantom; each repetition lasts less than 5 min and can be performed using a variety of isotropic test liquids. The proposed QA script checks for the linearity of G, the uniformity of Gmax across the field-of-view, the mutual agreement of gradient power across the three logical axes and the temporal stability. Optionally, the routine can correct for the mutual agreement of gradient power along the three axes, returning a set of gradient orientations to be used in data analysis. The effectiveness of the scheme in the presence of mismatched gradient amplitudes is reported using both simulations and in vivo data. The script is freely available online.

DAΦNE operation with electron-cloud-clearing electrodes.

The effects of an electron cloud (e-cloud) on beam dynamics are one of the major factors limiting performances of high intensity positron, proton, and ion storage rings. In the electron-positron collider DAΦNE, namely, a horizontal beam instability due to the electron-cloud effect has been identified as one of the main limitations on the maximum stored positron beam current and as a source of beam quality deterioration. During the last machine shutdown in order to mitigate such instability, special electrodes have been inserted in all dipole and wiggler magnets of the positron ring. It has been the first installation all over the world of this type since long metallic electrodes have been installed in all arcs of the collider positron ring and are currently used during the machine operation in collision. This has allowed a number of unprecedented measurements (e-cloud instabilities growth rate, transverse beam size variation, tune shifts along the bunch train) where the e-cloud contribution is clearly evidenced by turning the electrodes on and off. In this Letter we briefly describe a novel design of the electrodes, while the main focus is on experimental measurements. Here we report all results that clearly indicate the effectiveness of the electrodes for e-cloud suppression.

BCR/ABL1 fusion transcripts generated from alternative splicing: implications for future targeted therapies in Ph+ leukaemias.

Philadelphia (Ph+) positive leukaemias are an example of haematological malignant diseases where different chromosomal rearrangements involving both BCR and ABL1 genes generate a variety of chimeric proteins (BCR/ABL1 p210, p190 and p230) which are considered pathological "biomarkers". In addition to these three, there is a variety of fusion transcripts whose origin may depend either on diverse genetic rearrangement or on alternative/atypical splicing of the main mRNAs or on the occurrence of single-point mutations. Although the therapy of Ph+ leukaemias based on Imatinib represents a triumph of medicine, not all patients benefit from such drug and may show resistance and intolerance. Furthermore, interruption of Imatinib administration is often followed by clinical relapse, suggesting a failure in the eradication of residual leukaemic stem cells. Therefore, while the targeted therapy is searching for new and implemented pharmacological inhibitors covering all the possible mutations in the kinase domain, there is urge to identify alternative molecular targets to develop other specific and effective therapeutic approaches. In this review we discuss the importance of recent advances based on the discovery of novel BCR/ABL1 variants and their potential role as new targets/biomarkers of Ph+ leukaemias in the light of the current therapeutic trends. The limits of the pharmacological inhibitors used for treating the disease can be overcome by considering other targets than the kinase enzyme. Our evaluations highlight the potential of alternative perspectives in the therapy of Ph+ leukaemias.

Syndromic surveillance of epidemic-prone diseases in response to an influx of migrants from North Africa to Italy, May to October 2011.

Following civil unrest in North Africa early in 2011, there was a large influx of migrants in Italy. A syndromic surveillance system was set up in April to monitor the health of this migrant population and respond rapidly to any health emergency. In the first six months, the system produced 67 alerts across all syndromes monitored and four alarms. There were no health emergencies, however, indicating that this migration flow was not associated with an increased risk of communicable disease transmission in Italy.

Spatio-temporal anomalous diffusion in heterogeneous media by nuclear magnetic resonance.

In this paper, we describe nuclear magnetic resonance measurements of water diffusion in highly confined and heterogeneous colloidal systems using an anomalous diffusion model. For the first time, temporal and spatial fractional exponents, α and µ, introduced within the framework of continuous time random walk, are simultaneously measured by pulsed gradient spin-echo NMR technique in samples of micro-beads dispersed in aqueous solution. In order to mimic media with low and high level of disorder, mono-dispersed and poly-dispersed samples are used. We find that the exponent α depends on the disorder degree of the system. Conversely, the exponent µ depends on both bead sizes and magnetic susceptibility differences within samples. The new procedure proposed here may be a useful tool to probe porous materials and microstructural features of biological tissue.

Anisotropic anomalous diffusion assessed in the human brain by scalar invariant indices.

A new method to investigate anomalous diffusion in human brain, inspired by the stretched-exponential model proposed by Hall and Barrick, is proposed here, together with a discussion about its potential application to cerebral white matter characterization. Aim of the work was to show the ability of anomalous diffusion indices to characterize white matter structures, whose complexity is only partially accounted by diffusion tensor imaging indices. MR signal was expressed as a stretched-exponential only along the principal axes of diffusion; whereas, in a generic direction, it was modeled as a combination of three stretched-exponentials. Indices to quantify the tissue anomalous diffusion and its anisotropy, independently of the experiment reference frame, were derived. Experimental results, obtained on 10 healthy subjects at 3T, show that the new parameters are highly correlated to intrinsic local geometry when compared with Hall and Barrick indices. Moreover, they offer a different contrast in white matter regions when compared with diffusion tensor imaging. Specifically, the new indices show a higher capability to discriminate among areas of the corpus callosum associated to different distribution in axonal densities, thus offering a new potential tool to detect more specific patterns of brain abnormalities than diffusion tensor imaging in the presence of neurological and psychiatric disorders.

Response to the 2009 influenza A(H1N1) pandemic in Italy.

In Italy, the arrival of the 2009 pandemic influenza A(H1N1) virus triggered an integrated response that was mainly based on the 2006 National Pandemic Preparedness and Response Plan. In this article we analyse the main activities implemented for epidemiological surveillance, containment and mitigation of the pandemic influenza and the lesson learned from this experience. Overall, from week 31 (27 July ­ 2 August) of 2009 to week 17 (26 April ­ 2 May) of 2010, we estimate that there were approximately 5,600,000 cases of influenza-like illness (ILI) who received medical attention (with almost 2,000 laboratory-confirmed cases of pandemic influenza from May to October 2009). A total of 1,106 confirmed cases were admitted to hospital for serious conditions, of whom 532 were admitted to intensive care units. There were 260 reported deaths due to pandemic influenza. Approximately 870,000 first doses of the pandemic vaccine were administered, representing a vaccine coverage of 4% of the target population. One of the possible reasons for the low uptake of the pandemic vaccine in the target population could be the communication strategy adopted, for both the general population and healthcare workers, which turned out to be a major challenge. Active involvement of all health professionals (at local, regional and national level) in influenza pandemic preparedness and response should be encouraged in the future.

In vitro and in vivo MR evaluation of internal gradient to assess trabecular bone density.

Here we propose a new magnetic resonance (MR) strategy based on the evaluation of internal gradient (G(i)) to assess the trabecular bone (TB) density in spongy bone. Spongy bone is a porous system characterized by a solid trabecular network immersed in bone marrow and characterized by a different relative percentage of water and fats. Using a 9.4 T MR micro-imaging system, we first evaluated the relative water and fat G(i) as extracted from the Spin-Echo decay function in vitro of femoral head samples from calves. Indeed, the differential effects of fat and water diffusion result in different types of G(i) behavior. Using a clinical MR 3T scanner, we then investigated in vivo the calcanei of individuals characterized by different known TB densities. We demonstrate, on these samples, that water is more prevalent in the boundary zone, while fats are rearranged primarily in the central zone of each pore. In vitro experiments showed that water G(i) magnitude from the samples was directly proportional to their TB density. Similar behavior was also observed in the clinical measures. Conversely, fat G(i) did not provide any information on spongy-bone density. Our results suggest that water G(i) may be a reliable marker to assess the status of spongy bone.

Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats.

RATIONALE: Methamphetamine is a highly addictive psychostimulant, and chronic methamphetamine users show high rates of relapse. Furthermore, prolonged methamphetamine abuse can lead to psychiatric symptoms and has been associated with various cognitive dysfunctions. However, the impact of self-administered methamphetamine on cognitive dysfunction and relapse has not been concurrently examined in an animal model. OBJECTIVES: The present study determined the effects of short- vs. long-access contingent methamphetamine on self-administration, extinction responding, reinstatement of methamphetamine seeking, and cognitive performance on an object exploration task. MATERIALS AND METHODS: Long-Evans rats self-administered methamphetamine i.v. (0.02 mg/infusion) or received saline during daily sessions (1 or 2 h) for 10 days, followed by either maintained short- (1 or 2 h) or long-access (6 h) self-administration for 14 days. Lever responding was extinguished prior to reinstatement, which consisted of presentation of drug-paired cues or a priming injection of methamphetamine (1.0 mg/kg). Animals were also tested on an object exploration task prior to self-administration and at 10-12 days after cessation of self-administration, thus providing a comparison of pre-methamphetamine exposure with post-methamphetamine exposure. RESULTS: Long-access methamphetamine self-administration resulted in escalation of daily intake. Furthermore, animals in both short- and long-access groups showed robust conditioned-cued and drug-primed reinstatement, with long access resulting in enhanced methamphetamine-primed reinstatement. Methamphetamine self-administration also led to access-dependent impairments on novel object recognition but failed to impair recognition of spatial reconfiguration. CONCLUSIONS: Extended methamphetamine self-administration enhances drug-primed reinstatement and decreases novel object recognition, indicating that prolonged contingent methamphetamine increases motivation for drug seeking following withdrawal while increasing cognitive deficits.

Measurement of electron clouds in large accelerators by microwave dispersion.

Clouds of low energy electrons in the vacuum beam pipes of accelerators of positively charged particle beams present a serious limitation for operation at high currents. Furthermore, it is difficult to probe their density over substantial lengths of the beam pipe. We have developed a novel technique to directly measure the electron cloud density via the phase shift induced in a TE wave transmitted over a section of the accelerator and used it to measure the average electron cloud density over a 50 m section in the positron ring of the PEP-II collider at the Stanford Linear Accelerator Center.

Second-line chemotherapy for non-small cell lung cancer.

Despite being considered a standard of care, administration of second-line chemotherapy for non-small cell lung cancer is limited to patients in good performance status (ECOG PS 0-1) and to selected patients with PS 2. Drugs currently approved by FDA in this setting are docetaxel, gefitinib, erlotinib and pemetrexed, while in Europe those registered with this indication are only docetaxel and pemetrexed. This short review will focus on the role of pemetrexed, from the controlled phase II trial, to the development of the vitamin supplementation strategy to decrease toxicity, to the large phase III registration trial undertaken vs. the standard docetaxel. Moreover, the huge patient material collected during this latter trial has lead to further analyses to clarify several aspects of second-line treatment, from toxicity to quality of life assessment, to its role in elderly patients and to the direct translation in terms of costs. Finally, we will give a brief overview on current trials, that mainly explore the possibility to raise pemetrexed dose, and thus to increase its activity while maintaining an acceptable toxicity.

Locally advanced non-small cell lung cancer: role of induction chemotherapy in resectable N2 disease.

Patients with resectable stage IIIA-N2 non-small cell lung cancer should receive induction chemotherapy before surgery. The aim is to early control systemic disease, eventually cure the mediastinal tumor spread and improve patients' survival. A recent metanalysis of randomized trials with second-generation platinum-based combinations has reinforced the evidence concerning the benefit of induction chemotherapy followed by surgery versus surgery alone in resectable disease. Moreover a large number of phase II trials have explored the activity and feasibility of platinum-based combinations with third-generation drugs in the same setting. Still opened questions to address with current clinical research are the eventual role of radiotherapy as induction treatment, the impact of definite chemoradiation versus induction treatment followed by surgical resection on local control and survival and finally the non-easy choice between neo-adjuvant and adjuvant chemotherapy.

Correlation between anemia and functional/cognitive capacity in elderly lung cancer patients treated with chemotherapy.

BACKGROUND: Elderly cancer patients are often excluded from clinical trials and no data are available on the impact of chemotherapy-related anemia on their functional status and cognitive functions. This observational study investigates the association between hemoglobin (Hb) level and comprehensive geriatric assessment (CGA) variables (MMSE, ADL/IADL, GDS, CIRS and VAS). PATIENTS AND METHODS: We enrolled 42 consecutive lung cancer elderly patients undergoing chemotherapy that were evaluated at baseline and after each CT cycle at least until cycle 2. Hb association with CGA indexes was expressed using Spearman's non-parametric coefficient r. RESULTS: Higher Hb values were significantly associated with more favourable values of all indexes measuring mental and functional capacity, depression and comorbidities. For all indexes except IADL, improvements from baseline were significantly related with concomitant Hb increases. In 14 patients given erythropoietin during the first two cycles, mean Hb increased from 9.2 to 10.8 g/dl, and the mean values of all CGA indexes were improved. On the contrary, in 18 patients not given erythropoietin, Hb varied from 13.0 to 11.2 g/dl and a parallel worsening in all CGA indexes was observed. CONCLUSIONS: Chemotherapy-related anemia is associated with impairment of functional status and cognitive functions. In elderly cancer patients anemia correction or maintenance could be useful to preserve functional independency and protect from mental decay. However, the study results need to be confirmed on a larger series of patients within a controlled clinical trial.

Diabetic rats treated by low molecular weight heparin OP 2123/parnaparin: morphological changes in the kidney and heart.

AIM: Early morphological alterations in the rat kidney and heart due to experimentally induced diabetes are described in order to evaluate the possible therapeutic role of low molecular weight heparin (LMWH; OP 2123/parnaparin). METHODS: Our findings concern the alterations observed in the rat kidney and heart because these are the organs (together with the retina) mainly involved in the early morphological angiopathic modifications associated with diabetic damage of organs and tissues. In diabetic animals treated with LMWH, the Periodic Acid-Schiff (PAS) reaction showed a slight decrease when compared with the diabetic control group. Photographs were submitted to the quantitative analysis of images using a Quantimet 500 Image Analyzer (Leica) equipped with specific software. The following parameters were measured: (1) total area occupied by alkaline phosphatase (AP)-positive capillaries; (2) number and diameter of AP-positive capillaries; (3) distribution and total area occupied by PAS-positive structures (related to the intensity of the reaction resulting from the different amount of mucopolysaccharides). RESULTS: LMWH treatment is efficient in preventing these modifications, above all in the kidney. The histological study of the heart and kidney shows no significant, relevant alterations. However, the histological study of the mucopolysaccharides in diabetic animals highlighted a tendency for the heart to accumulate these substances. LMWH treatment only modestly reduced this accumulation. CONCLUSIONS: Previous evidence demonstrating a beneficial effect of therapy based on heparan sulphate proteoglycans and/or other heparin-like substances in insulin-dependent diabetes mellitus seems to be confirmed by our experimental results in different organs of adult rats. In fact, parnaparin treatment is effective (in our experience) for ameliorating the morphological pattern observed early in some diabetic tissues of rats and, above all, in the kidney.