New approaches to the management of adult acute lymphoblastic leukemia

Traditional treatment regimens for adult acute lymphoblastic leukemia, including allogeneic hematopoietic cell transplantation, result in an overall survival of about 40%, a figure hardly comparable with the extraordinary 80-90% cure rate currently reported in children. When translated to the adult setting, modern pediatric-type regimens improve the survival to about 60% in young adults. The addition of tyrosine kinase inhibitors for patients with Philadelphia chromosome positive disease and the measurement of minimal residual disease to guide risk stratification and post-remission approaches has led to further improvements in outcomes. Relapsed disease and treatment toxicity - sparing no patient but representing a major concern especially in the elderly - are the most critical current issues awaiting further therapeutic advancement. Recently, there has been considerable progress in understanding the disease biology, specifically the Philadelphia-like signature as well as other high-risk subgroups. In addition, there are several new agents that will undoubtedly contribute to further improvement in the current outcomes. The most promising agents are new the monoclonal antibodies, immunomodulators, and chimeric antigen receptor T cells and, to a lesser extent, several new drugs targeting key molecular pathways involved in leukemic cell growth and proliferation. This review examines the evidence supporting the increasing role of the new therapeutic tools and treatment options in different disease subgroups, including frontline and relapsed/refractory disease. It is now possible to define the best individual approach based on to the emerging concepts of precision medicine

Swimming using surface acoustic waves

Microactuation of free standing objects in fluids is currently dominated by the rotary propeller, giving rise to a range of potential applications in the military, aeronautic and biomedical fields. Previously, surface acoustic waves (SAWs) have been shown to be of increasing interest in the field of microfluidics, where the refraction of a SAW into a drop of fluid creates a convective flow, a phenomenon generally known as SAW streaming. We now show how SAWs, generated at microelectronic devices, can be used as an efficient method of propulsion actuated by localised fluid streaming. The direction of the force arising from such streaming is optimal when the devices are maintained at the Rayleigh angle. The technique provides propulsion without any moving parts, and, due to the inherent design of the SAW transducer, enables simple control of the direction of travel

The high-intensity hyperon beam at CERN

A high-intensity hyperon beam was constructed at CERN to deliver Sigma- to experiment WA89 at the Omega facility and operated from 1989 to 1994. The setup allowed rapid changeover between hyperon and conventional hadron beam configurations. The beam provided a Sigma-flux of 1.4 x 10^5 per burst at mean momenta between 330 and 345 Gev/c, produced by about 3 x 10^10 protons of 450 GeV/c . At the experiment target the beam had a Sigma-/pi- ratio close to 0.4 and a size of 1.6 x 3.7 cm^2. The beam particle trajectories and their momenta were measured with a scintillating fibre hodoscope in the beam channel and a silicon microstrip detector at the exit of the channel. A fast transition radiation detector was used to identify the pion component of the beam.Comment: 20 pages, 13 figures. Submitted to Nucl. Instr. Meth.

Extremely Low Loss Phonon-Trapping Cryogenic Acoustic Cavities for Future Physical Experiments

Low loss Bulk Acoustic Wave devices are considered from the point of view of the solid state approach as phonon-confining cavities. We demonstrate effective design of such acoustic cavities with phonon-trapping techniques exhibiting extremely high quality factors for trapped longitudinally-polarized phonons of various wavelengths. Quality factors of observed modes exceed 1 billion, with a maximum $Q$-factor of 8 billion and $Q\times f$ product of $1.6\cdot10^{18}$ at liquid helium temperatures. Such high sensitivities allow analysis of intrinsic material losses in resonant phonon systems. Various mechanisms of phonon losses are discussed and estimated

Location-independent and location-linked representations of sound objects.

For the recognition of sounds to benefit perception and action, their neural representations should also encode their current spatial position and their changes in position over time. The dual-stream model of auditory processing postulates separate (albeit interacting) processing streams for sound meaning and for sound location. Using a repetition priming paradigm in conjunction with distributed source modeling of auditory evoked potentials, we determined how individual sound objects are represented within these streams. Changes in perceived location were induced by interaural intensity differences, and sound location was either held constant or shifted across initial and repeated presentations (from one hemispace to the other in the main experiment or between locations within the right hemispace in a follow-up experiment). Location-linked representations were characterized by differences in priming effects between pairs presented to the same vs. different simulated lateralizations. These effects were significant at 20-39 ms post-stimulus onset within a cluster on the posterior part of the left superior and middle temporal gyri; and at 143-162 ms within a cluster on the left inferior and middle frontal gyri. Location-independent representations were characterized by a difference between initial and repeated presentations, independently of whether or not their simulated lateralization was held constant across repetitions. This effect was significant at 42-63 ms within three clusters on the right temporo-frontal region; and at 165-215 ms in a large cluster on the left temporo-parietal convexity. Our results reveal two varieties of representations of sound objects within the ventral/What stream: one location-independent, as initially postulated in the dual-stream model, and the other location-linked

Neural plasticity associated with recently versus often heard objects.

In natural settings the same sound source is often heard repeatedly, with variations in spectro-temporal and spatial characteristics. We investigated how such repetitions influence sound representations and in particular how auditory cortices keep track of recently vs. often heard objects. A set of 40 environmental sounds was presented twice, i.e. as prime and as repeat, while subjects categorized the corresponding sound sources as living vs. non-living. Electrical neuroimaging analyses were applied to auditory evoked potentials (AEPs) comparing primes vs. repeats (effect of presentation) and the four experimental sections. Dynamic analysis of distributed source estimations revealed i) a significant main effect of presentation within the left temporal convexity at 164-215ms post-stimulus onset; and ii) a significant main effect of section in the right temporo-parietal junction at 166-213ms. A 3-way repeated measures ANOVA (hemisphere×presentation×section) applied to neural activity of the above clusters during the common time window confirmed the specificity of the left hemisphere for the effect of presentation, but not that of the right hemisphere for the effect of section. In conclusion, spatio-temporal dynamics of neural activity encode the temporal history of exposure to sound objects. Rapidly occurring plastic changes within the semantic representations of the left hemisphere keep track of objects heard a few seconds before, independent of the more general sound exposure history. Progressively occurring and more long-lasting plastic changes occurring predominantly within right hemispheric networks, which are known to code for perceptual, semantic and spatial aspects of sound objects, keep track of multiple exposures

SU(3) Breaking in Hyperon Beta Decays: a Prediction for Xi^0 -> Sigma^+ e nu-bar

On the basis of a previous analysis of hyperon semi-leptonic decay data, a prediction is presented for g_1/f_1 in the Xi^0 -> Sigma^+ e nu-bar beta-decay. The analysis takes into account SU(3) breaking in this sector via the inclusion of mass-driven corrections. A rather precise measurement of the above channel by the KTeV experiment at Fermilab will shortly be available. Since the dependence on the SU(3) parameters, F and D, is identical to that of the neutron beta-decay, such a measurement will provide a rather stringent test of SU(3) and the models used to describe its violation in these decays. The prediction given here for the above decay is g_1/f_1=1.17, which leads to a rate of 0.80 x 10^6 s^-1 and thus a branching fraction of 2.3 x 10^-4.Comment: LaTeX, 7 pages, uses acromake, cite and topcapt packages. Non-printing extended ascii characters replaced plus minor correction

Patient perspectives on an intervention after suicide attempt: The need for patient centred and individualized care.

Many types of intervention exist for suicide attempters, but they tend not to sufficiently consider patient's views. To identify useful components of a previously evaluated intervention after a suicide attempt from the patient's views and to better understand the process of recovery. Forty-one interviews with suicide attempters were qualitatively analysed. Views of participants (i) on the components of the intervention (nurse case-management, joint crisis plan, meetings with relatives/network and follow-up calls) and (ii) their recovery were explored. The material was analysed by means of thematic analysis with a deductive-inductive approach. Participants valued the human and professional qualities of the nurse case-manager, and appreciated follow-up calls and meetings. However, their views diverged regarding for instance frequency of phone calls, or disclosing information or lack thereof. Interpersonal relationship, suicide attempters' own resources and life changes emerged as core recovery factors. The study highlights the figure of an engaged clinician, with both professional and human commitment, aware that some suicide attempters put more emphasis on their own resources than on delivered health care. Interventions should consider the clinician as the cornerstone of the tailored care valued by suicide attempters

Calling situated: a survey among medical students supplemented by a qualitative study and a comparison with a surveyed sample of physicians.

Calling within the medical context receives growing academic attention and empirical research has started to demonstrate its beneficial effects. The purpose of this study is to investigate what motivates students to enter medical school and what role calling may play (i), to evaluate if calling influences the way in which they experience their studies (ii), and to compare medical students' experience of calling with those of physicians. A questionnaire survey was distributed among medical students (N = 1048; response rate above 60%) of the University of Lausanne in Switzerland. It was supplemented by a group discussion between bachelor medical students (N = 8) and senior physicians (N = 4), focusing on different facets of calling. An existing data set of a survey among physicians, addressing calling with the same questionnaire, was used to compare students' and physicians' attitudes towards calling. Survey data were analyzed with the habitual statistical procedures for categorical and continuous variables. The group discussion was analyzed with thematic analysis. The survey showed that experiencing calling is a motivational factor for study choice and influences positively choice consistency. Students experiencing calling differed from those who did not: they attributed different definitions to calling, indicated more often prosocial motivational factors for entering medical school and perceived the learning context as less burdensome. The analysis of the group discussion revealed that the concept of calling has a fluid definition. It was conceived as having the characteristics of a double-edged sword and as originating from within or outside or from a dialectic interplay between the inner and outer world. Finally, calling is experienced less often by physicians than by medical students, with a decreasing prevalence as the immersion in the clinical years of the study of medicine progresses. Calling plays an important role in study choice and consistency of medical students. Given its relevance for medical students and its ramifications with the learning context, calling should become a topic of the reflexive parts of the medical curriculum. We critically discuss the role played by calling for medical students and provide some perspectives on how calling could be integrated in the reflection and teaching on physicianhood