No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication.

HIV persistence during combination antiretroviral therapy (cART) is the principal obstacle to cure. Mechanisms responsible for persistence remain uncertain; infections may be maintained by persistence and clonal expansion of infected cells or by ongoing replication in anatomic locations with poor antiretroviral penetration. These mechanisms require different strategies for eradication, and determining their contributions to HIV persistence is essential. We used phylogenetic approaches to investigate, at the DNA level, HIV populations in blood, lymphoid, and other infected tissues obtained at colonoscopy or autopsy in individuals who were on cART for 8 to 16 years. We found no evidence of ongoing replication or compartmentalization of HIV; we did detect clonal expansion of infected cells that were present before cART. Long-term persistence, and not ongoing replication, is primarily responsible for maintaining HIV. HIV-infected cells present when cART is initiated represent the only identifiable source of persistence and is the appropriate focus for eradication.

Quality of life in long-term survivors treated for metastatic medulloblastoma with a hyperfractionated accelerated radiotherapy (HART) strategy.

PURPOSE: An intensive therapeutic strategy for metastatic medulloblastoma was launched in 1998 in our Institution. The aim of this study was to examine the long-term quality of life (QoL) in survivor patients at least 3 years after the end of the treatment. METHODS: Patients were asked to complete self-administered QoL questionnaires. An index of physical impairment (IPI) was scored (range 0-100; the lower the score the better) based on clinical objective observations. Patients were divided into two groups (lower IPI group, and higher IPI group) and descriptively compared accordingly. RESULTS: The study was completed by 25/33 eligible patients. Despite patients with a higher IPI reported worse perceived health condition, they had better emotional and psychological scores than those with a lower IPI in all QoL questionnaires. CONCLUSION: In our sample, patients with more severe objective and perceived physical impairments reported a better psychosocial QoL, possibly because the greater attention paid to them by society and family contributes to a better adjustment in long-term survivors. On this base, it should be recommended that all survivors receive a strong support as the most impaired patients.

Recovering from chronic myeloid leukemia: the patients' perspective seen through the lens of narrative medicine.

PURPOSE: The main objective of this study is to gain a deeper understanding of how patients suffering from chronic myeloid leukemia (CML) cope with their illness. The study aims to reconstruct the subjective meaning-making process related to CML in order to gain insights into the impact the disease has on patients' emotions and everyday lives, as well as to explore the psychological impact of their being presented with the chance to suspend their therapy and recover from the disease. METHODS: Data were gathered from a qualitative study conducted in Italy on 158 Italian CML patients. Basing the study on the narrative inquiry approach, the patients were required to describe their patient journey in a qualitative narrative diary. These contained prompts to elicit the free expression of their needs, expectations, and priorities. A lexicographic analysis was carried out with T-LAB software and in particular a thematic analysis of elementary contexts (TAECs) and a word association analysis (WAA). RESULTS: The TAEC detected four thematic clusters related to two factors (temporal frame and contextual setting) that explained the variance among the narratives. The WAA evidenced a wide variety of emotions, both positive and negative, as patients reacted to the possibility of interrupting their therapy. CONCLUSIONS: A better understanding of patients' experiences can offer insights into promoting the development of more sustainable healthcare services and into therapeutic innovation aimed at improving patients' quality of life and at engaging them more in their treatment. The findings of this study can also help make medical professionals more aware of the patient's burden and help them identify potential interactions and emotional levers to improve clinical relationships.

HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells.

The persistence of HIV-infected cells in individuals on suppressive combination antiretroviral therapy (cART) presents a major barrier for curing HIV infections. HIV integrates its DNA into many sites in the host genome; we identified 2410 integration sites in peripheral blood lymphocytes of five infected individuals on cART. About 40% of the integrations were in clonally expanded cells. Approximately 50% of the infected cells in one patient were from a single clone, and some clones persisted for many years. There were multiple independent integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. Our findings show that HIV integration sites can play a critical role in expansion and persistence of HIV-infected cells.

[Psycho-organic diseases in children and adolescents affected by pediatric neoplasms]. / Disturbi psico-organici in bambini e adolescenti affetti da neoplasie pediatriche.

At Pediatric Oncology Centers, psychological intervention and psychotherapy are generally offered to children and adolescents for supporting their adjustment to disease and treatment. The clinical practice, however, point out that cognitive and emotional symptoms, such as psychic distortions, fatigue, anxiety, irritability and depression, are sustained by biological mechanisms connected with disease and treatment and not respondent to psychological consultation and to other psychosocial resources. These manifestations could interfere with treatment or with the long-term adjustment and call for psychopharmacological treatments. Biological factors able to cause these alterations are not yet studied in depth in clinical tradition and scientific literature on the integration of psychological and psychopharmacological intervention in pediatric oncology is still poor. In this paper organic components of psychic and behavioral alterations in the course of disease are illustrated, considering the symptoms, causes and possible remedies in the light of the most recent interdisciplinary views. The main mechanism connected with oncologic treatments - chemotherapy, surgery, radiotherapy - and responsible for psycho-organic alterations in children and adolescent with cancer are also described.

Rayleigh wave scattering from sessile droplets.

Radiation of energy by large-amplitude leaky Rayleigh waves is regarded as one of the key physical mechanisms regulating the actuation and manipulation of droplets in surface acoustic wave (SAW) microfluidic devices. The interaction between a SAW and a droplet is highly complex and is presently the subject of extensive research. This paper investigates the existence of an additional interaction mechanism based on the propagation of quasi-Stoneley waves inside sessile droplets deposited on a solid substrate. In contrast with the leaky Rayleigh wave, the energy of the Stoneley wave is confined within a thin fluid layer in contact with the substrate. The hypothesis is confirmed by three-dimensional finite element simulations and ultrasonic scattering experiments measuring the reflection of Rayleigh waves from droplets of different diameters. Moreover, real-time monitoring of the droplet evaporation process reveals a clear correlation between the droplet contact angle and the spectral information of the reflected Rayleigh signal, thus paving the way for ultrasonic measurements of surface tension.

Combining time of flight and diffraction tomography for high resolution breast imaging: initial in vivo results (L).

Ultrasound tomography (UST) is being developed to address the limitations of mammography in breast cancer detection. Central to the success of UST is the possibility of obtaining high-resolution images of tissue mechanical properties across the whole breast. A recent paper [Huthwaite and Simonetti, J. Acoust. Soc. Am. 130, 1721-1734 (2011)] made use of a numerical phantom to demonstrate that sufficient image resolution can be obtained by simply treating refraction and diffraction effects in consecutive steps through the combination of ray-based time of flight and diffraction tomography. This letter presents the first experimental demonstration of the method using phantom and invivo data from a cancer patient.

High-resolution imaging without iteration: a fast and robust method for breast ultrasound tomography.

Breast ultrasound tomography has the potential to improve the cost, safety, and reliability of breast cancer screening and diagnosis over the gold-standard of mammography. Vital to achieving this potential is the development of imaging algorithms to unravel the complex anatomy of the breast and its mechanical properties. The solution most commonly relied upon is time-of-flight tomography, but this exhibits low resolution due to the presence of diffraction effects. Iterative full-wave inversion methods present one solution to achieve higher resolution, but these are slow and are not guaranteed to converge to the correct solution. Presented here is HARBUT, the hybrid algorithm for robust breast ultrasound tomography, which utilizes the complementary strengths of time-of-flight and diffraction tomography resulting in a direct, fast, robust and accurate high resolution method of reconstructing the sound speed through the breast. The algorithm is shown to produce accurate reconstructions with realistic data from a complex three-dimensional simulation, with masses as small as 4 mm being clearly visible.

Diffraction and coherence in breast ultrasound tomography: a study with a toroidal array.

Ultrasound is commonly used as an adjunct to mammography for diagnostic evaluation of suspicions arising from breast cancer screening. As an alternative to conventional sonography that uses hand-held transducers, toroidal array probes that encircle the breast immersed in a water bath have been investigated for ultrasound tomography. In this paper, two sets of experiments performed with a prototype ultrasound scanner on a phantom and a human breast in vivo are used to investigate the effects of diffraction and coherence in ultrasound tomography. Reconstructions obtained with transmission diffraction tomography (TDT) are compared with conventional reflection imaging and computerized ultrasound tomography showing a substantial improvement. The in vivo tests demonstrate that TDT can image the complex boundary of a cancer mass and suggest that it can reveal the anatomy of milk ducts and Cooper's ligaments.

Imaging beyond the Born approximation: an experimental investigation with an ultrasonic ring array.

The classical diffraction limit excludes the possibility of resolving features of an object which are spaced less than half a wavelength apart when scattering experiments are performed from the far field. However, recently it has been shown that this limit could be a consequence of the Born approximation that neglects the distortion of the probing wave as it travels through the object to be imaged. Such a distortion, which is due to the multiple scattering phenomenon, can encode unlimited resolution in the radiating component of the scattered field thus leading to super resolution. In this context, a resolution better than lambda/3 has been reported in the case of elastic wave probing [F. Simonetti, Phys. Rev. E 73, 036619 (2006)], lambda being the wavelength of the wave illuminating the object. This paper demonstrates a resolution better than lambda/4 and approaching lambda/6 for objects immersed in a water bath probed by means of a ring transducer array that excites and detects ultrasonic pressure waves in a full view configuration. This is achieved despite the presence of a high level of noise in the measurements (the signal to noise ratio was below 0 dB). Moreover, while previous papers have provided experimental evidence of super resolution for objects small compared to the wavelength, here the case of extended objects is also investigated.

Transitory, spontaneously recovering, peripheral facial nerve palsy after vinorelbine administration.

Childhood intrinsic brain-stem gliomas have a dismal prognosis. Different treatment strategies have been adopted over the years without changing the final outcome of this ominous disease. Due to this grim prognosis, experimental therapeutic designs are worthwhile. Vinorelbine is a semi-synthetic vinca alkaloid that has demonstrated a broad spectrum of activity both in in vitro and in vivo experimental systems. By adopting vinorelbine during and after focal radiotherapy in the last two years, we have tried to evocate its known synergistic effect in brain-stem tumour control. Vinorelbine was administered intravenously before, during and after radiotherapy on tumour bed for a total duration of 10 months. All the consecutive patients whose clinical and radiological features corresponded to the diagnosis of an intrinsic brain-stem tumour, i.e., diffuse pontine glioma, have been accrued to this treatment protocol since July 2002. A histological assessment was not required. All patients were treated during hospital stay or in the outpatient clinic at the Istituto Nazionale Tumori of Milan (n=12) and at the Pediatric Clinic of Policlinico in Catania (n=1). Two of the thirteen patients so far treated have developed multiple subsequent, and transitory, episodes of monolateral peripheral facial nerve palsy during vinorelbine administration. The palsy always completely and spontaneously resolved at a short interval-around 30 min-after the end of the drug infusion. Obvious tumour progression was excluded by means of MRI; therefore the drug was administered as scheduled until the end of the treatment. We describe possible neurological and oncological implications of this unusual side effect, until now not reported in any other series dealing with vinorelbine as adjuvant treatment.

[Application of the legislation on safety occupational hygiene in the Military Navy]. / Applicazione delle norme di sicurezza e d'igiene del lavoro in ambito Marina Militare.

The paper analyses the consequences of the promulgation legislative decree 626/94 on the sanitary organization of the Armed Forces and, particularly, of the Italian Military Navy. In this context, the authors describe the current safety and occupational hygiene organization, the tasks of the vigilance organs, and the actuative modalities of preventive measures on the ships (during navigation and in shipyard).

Multiple scattering: the key to unravel the subwavelength world from the far-field pattern of a scattered wave.

For more than a century the possibility of imaging the structure of a medium with diffracting wave fields has been limited by the tradeoff between resolution and imaging depth. While long wavelengths can penetrate deep into a medium, the resolution limit precludes the possibility of observing subwavelength structures. Near-field microscopy has recently demonstrated that the resolution limit can be overcome by bringing a probing sensor within one wavelength distance from the surface to be imaged. This paper extends the scope of near-field microscopy to the reconstruction of subwavelength structures from measurements performed in the far-field. It is shown that the distortion undergone by a wave field as it travels through an inhomogeneous medium and the subsequent generation of local evanescent fields encode subwavelength information in the far-field due to multiple scattering within the medium. This argument is proved theoretically and supported by a limited view experiment performed with elastic waves in which an image with a resolution better than a third of the wavelength is achieved.

On the meaning of Lamb mode nonpropagating branches.

The modes of vibration of an elastic plate are usually divided into propagating and nonpropagating kinds. While nonpropagating modes characterize local vibration nearby a perturbation source, which can be either an external force or a geometrical discontinuity, propagating modes carry energy along the waveguide and account for the vibration far away from the perturbation source. In this paper, by considering that the modes of an absorbing plate are always propagating, it is shown that each elastic mode consists of propagating and nonpropagating branches, which turn into a single propagating mode as soon as internal absorption is considered. Moreover, it is shown how introducing a little material damping leads to a rigorous differentiation of elastic modes when they are connected. A similar result can be obtained by loading the plate with a light fluid [Rokhlin et al., J. Acoust. Soc. Am. 85, 1074-1080 (1989)].

Ultrasonic interferometry for the measurement of shear velocity and attenuation in viscoelastic solids.

A method for the measurement of the shear properties of solid viscoelastic materials is presented. The viscoelastic material is cut into a cylindrical sample which is clamped between two rods. The transmission and reflection coefficient spectra of the fundamental torsional mode through the sample are measured by means of two pairs of piezoelectric transducers placed at the free ends of the rod-sample-rod system. Such spectra exhibit maxima and minima which occur approximately at the resonance frequencies of the free viscoelastic cylinder. Therefore, the shear velocity can be obtained by measuring the frequency interval between two consecutive maxima or minima. The shear attenuation is derived by best fitting the analytical expression of the reflection and transmission coefficients to the experimental spectra. The test is very quick to set up as the sample is simply clamped between the two rods.

A guided wave technique for the characterization of highly attenuative viscoelastic materials.

The measurement of the acoustic properties of highly attenuative materials such as bitumen is very difficult. One possibility is to use measurements of the extent to which filling a cylindrical waveguide with the material affects the dispersion relationship of the cylinder. Torsional modes have been excited using piezoelectric transducers placed at one end of the cylinder, while the phase velocity and attenuation spectra have been measured by means of laser scanning. At each frequency, under the hypothesis of linear viscoelasticity, the phase velocity and attenuation of the fundamental torsional mode have been calculated as a function of the bulk shear velocity and the bulk shear attenuation of the inner core at that frequency. The resulting phase velocity and guided wave attenuation contour plots have been employed for deriving the unknown shear properties from the measured velocity and attenuation of the guided wave. The monochromaticity of the approach has not required a particular frequency dependence of the material properties to be assumed. Results for bitumen are given.

Efecto de la maniobra inspiratoria y de la hiperinsuflación pulmonar en los flujos espiratorios máximos en pacientes con fibrosis quística / Effect of inspiratory maneuver and lung hyperinflation on maximal expiratory flow-volume curves in cystic fibrosis patients

El tiempo inspiratorio previo a la realización de una maniobra espiratoria forzada máxima (FEM) es una variable que no ha sido completamente estudiada en Fibrosis Quística (FQ). El objetivo de este estudio fue evaluar la hipótesis que niños con FQ tendrían mayores volúmenes y flujos espiratorios forzados al disminuir la duracion del tiempo inspiratorio. Se estudiaron 16 niños con FQ, en etapa estable, sin haber presentado una exacerbación respiratoria en los ultimos dos meses, (10 hombres), de edad 11,9 ñ 0,7 años (promedio ñ ES), con un FEV1 de 62,8 ñ 6,4 porciento predicho. Las pruebas de función pulmonar consistieron en la medición de volúmenes pulmonares estáticos y resistencia de la vía aérea, seguido de evaluación dinámica de la función pulmonar. Esta última medición fue precedida de 3 maniobras inspiratorias diferentes en forma aleatoria[inspiración y detención de 0 segundos (M0), 2 segundos (M2) o 5 segundos (M5)]. El grupo se dividió en pacientes con hiperinsuflación pulmonar detectada por VR/CPT > 30 porciento, (n=9) y sin hiperinsuflación pulmonar RV/CPT menor o igual 30 porciento (n=7). Los resultados demostraron que, en los pacientes con hiperinsuflación, VEF1 y CVF fueron 8,9 ñ 3,4 porciento (p<0,02) y 9,3 ñ 2,1 porciento (p > 0,001) mayores respectivamente, después de M0 en comparación a después de M2 y 2,4 ñ 2,8 porciento (p = ns) menor respectivamente después de M5 en relación a después de M2 (M0 vs M5:p<0,01 para ambos, VEF1 y CVF). En resumen, en pacientes portadores de fibrosis quística e hiperinsuflación, VEF1 y CVF son significativamente mayores luego de realizar una espiración sin detención de inspiración de 2 ó 5 segundos. Sugerimos que los mecanismos de relajación de la musculatura lisa del árbol bronquial pueden ser los responsables de este hallazgo

Intravascular lymphomatosis (IL) in a child mimicking a posterior fossa tumor.

Intravascular lymphomatosis (IL) is a rare entity only recently included in lymphoma classification, whose main feature is the exclusive or predominant growth of neoplastic cells within blood vessels. The vast majority of the patients affected by IL belong to the 7th or 8th decade of life and present with skin rash or CNS diffuse necrotic or demyelinating lesions. Case report. SS, a 13-year-old girl, was admitted to a Neurosurgery Unit because of endocranic hypertension, where, after CT and MRI documenting a IV ventricle 3 cm diameter tumor, she was submitted to complete tumor excision: extemporary diagnosis was suggestive of medulloblastoma. When referred to us she had persistent fever with normal blood and spinal fluid cultures. Whole CNS MRI did not give evidence of residual or metastatic disease while CSF cytology showed only pleiocytosis. Treatment was started according to our ongoing protocol for medulloblastoma with pre-radiation chemotherapy. Before delivering radiotherapy (RT), upon review of histologic specimens, the definitive diagnosis of IL B-phenotype was made. The girl was re-admitted and, after a complete re-staging, chemotherapy was intensified according to our schedule for high-grade B-cell lymphoma and CNS was irradiated up to a total dose of 25 Gy. She remained alive in continuous complete remission at 21 months after diagnosis. The case here reported is unique for age, tumor presentation, and, so far, favourable outcome, in spite of the delayed histological diagnosis.