Showing papers by "University of Milano-Bicocca published in 2007"

Matching NLO QCD computations with Parton Shower simulations: the POWHEG method

Abstract: The aim of this work is to describe in detail the POWHEG method, first suggested by one of the authors, for interfacing parton-shower generators with NLO QCD computations. We describe the method in its full generality, and then specify its features in two subtraction frameworks for NLO calculations: the Catani-Seymour and the Frixione-Kunszt-Signer approach. Two examples are discussed in detail in both approaches: the production of hadrons in e+e− collisions, and the Drell-Yan vector-boson production in hadronic collisions.

2007 ESH-ESC guidelines for the management of arterial hypertension - The task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the European society of cardiology (ESC)

Abstract: Authors/Task Force Members: Giuseppe Mancia, Co-Chairperson (Italy), Guy De Backer, Co-Chairperson (Belgium), Anna Dominiczak (UK), Renata Cifkova (Czech Republic) Robert Fagard (Belgium), Giuseppe Germano (Italy), Guido Grassi (Italy), Anthony M. Heagerty (UK), Sverre E. Kjeldsen (Norway), Stephane Laurent (France), Krzysztof Narkiewicz (Poland), Luis Ruilope (Spain), Andrzej Rynkiewicz (Poland), Roland E. Schmieder (Germany), Harry A.J. Struijker Boudier (Netherlands), Alberto Zanchetti (Italy)

A Positive-weight next-to-leading-order Monte Carlo for heavy flavour hadroproduction

Abstract: We present a next-to-leading order calculation of heavy flavour production in hadronic collisions that can be interfaced to shower Monte Carlo programs. The calculation is performed in the context of the POWHEG method [1]. It is suitable for the computation of charm, bottom and top hadroproduction. In the case of top production, spin correlations in the decay products are taken into account.

Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data.

Abstract: Most modern treatment protocols for acute lymphoblastic leukaemia (ALL) include the analysis of minimal residual disease (MRD). To ensure comparable MRD results between different MRD-polymerase chain reaction (PCR) laboratories, standardization and quality control are essential. The European Study Group on MRD detection in ALL (ESG-MRD-ALL), consisting of 30 MRD-PCR laboratories worldwide, has developed guidelines for the interpretation of real-time quantitative PCR-based MRD data. The application of these guidelines ensures identical interpretation of MRD data between different laboratories of the same MRD-based clinical protocol. Furthermore, the ESG-MRD-ALL guidelines will facilitate the comparison of MRD data obtained in different treatment protocols, including those with new drugs.

Optimizing the photocatalytic properties of hydrothermal TiO2 by the control of phase composition and particle morphology. a systematic approach.

Abstract: The possibility of controlling the photocatalytic activity of TiO2 nanoparticles by tailoring their crystalline structure and morphology is a current topic of great interest. In this study, a broad variety of well-faceted particles with different phase compositions, sizes, and shapes have been obtained from concentrated TiOCl2 solutions by systematically changing temperature, pH, and duration of the hydrothermal treatment. The guide to select the suitable experimental conditions was provided by thermodynamic modeling based on available thermochemical data. By combining the results of TEM, HRTEM, XRD, density, and specific surface area measurements, a complete structural and morphological characterization of the particles was performed. Correlation between the photocatalytic activity in the UV photodegradation of phenol solutions and the particle size was established. Prismatic rutile particles with length/width ratio around 5 and breadth of 60−100 nm showed the highest activity. The surface chemistry of t...

The sympathetic nervous system and the metabolic syndrome.

Abstract: Studies performed in the past two decades have unequivocally shown that several of the components of the metabolic syndrome are associated with indirect and direct markers of adrenergic overdrive. This is the case for hypertension and obesity, in which resting tachycardia, elevated plasma norepinephrine values, increased sympathetic nerve traffic, as well as augmented levels of total and regional norepinephrine spillover have been reported. This is also the case for insulin resistance, i.e. a metabolic condition frequently complicating the various components of the pathological condition identified as the 'metabolic syndrome'. After briefly describing the epidemiological and the cardiovascular risk profile of the disease, this paper will examine the behaviour of the sympathetic nervous system in the metabolic syndrome as well as the mechanisms potentially responsible for this neurogenic abnormality. This will be followed by an analysis of the role played by neuroadrenergic factors in disease progression as well as in the pathogenesis of its complications. Finally, the therapeutic implications of these findings will be highlighted.

Long-Term Prognostic Value of Blood Pressure Variability in the General Population. Results of the Pressioni Arteriose Monitorate e Loro Associazioni Study

Abstract: The hypothesis has been advanced that cardiovascular prognosis is related not only to 24-hour mean blood pressure but also to blood pressure variability. Data, however, are inconsistent, and no long-term prognostic study is available. In 2012 individuals randomly selected from the population of Monza (Milan), 24-hour ambulatory blood pressure (Spacelabs 90207) was measured via readings spaced by 20 minutes. Systolic and diastolic blood pressure variability was obtained by calculating the following: (1) the SD of 24-hour, day, and night mean values; (2) the day-night blood pressure difference; and (3) the residual or erratic blood pressure variability (Fourier spectral analysis). Fatal cardiovascular and noncardiovascular events were registered for 148 months. When adjusted for age, sex, 24-hour mean blood pressure, and other risk factors, there was no relationship between the risk of death and 24-hour, day, and night blood pressure SDs. In contrast, the adjusted risk of cardiovascular death was inversely related to day-night diastolic BP difference (beta coefficient=-0.040; P<0.02) and showed a significant positive relationship with residual diastolic blood pressure variability (beta coefficient=0.175; P<0.002). Twenty-four-hour mean blood pressure attenuation of nocturnal hypotension and erratic diastolic blood pressure variability all independently predicted the mortality risk, with the erratic variability being the most important factor. Our data show that the relationship of blood pressure to prognosis is complex and that phenomena other than 24-hour mean values are involved. They also provide the first evidence that short-term erratic components of blood pressure variability play a prognostic role, with their increase being accompanied by an increased cardiovascular risk.

Matching NLO QCD computations with Parton Shower simulations: the POWHEG method

Abstract: The aim of this work is to describe in detail the POWHEG method, first suggested by one of the authors, for interfacing parton-shower generators with NLO QCD computations. We describe the method in its full generality, and then specify its features in two subtraction frameworks for NLO calculations: the Catani-Seymour and the Frixione-Kunszt-Signer approach. Two examples are discussed in detail in both approaches: the production of hadrons in e+e- collisions, and the Drell-Yan vector-boson production in hadronic collisions.

Control of the charge state of metal atoms on thin MgO films.

Abstract: The identification of concepts which allow understanding and subsequently tuning the catalytic properties of heterogeneous catalysts is still one of the key issues of research in catalysis. A variety of different strategies have been put forward over the last decades in the effort to compass and establish a rational design of heterogeneous catalysts [1]. Most of these strategies are based on structure reactivity relationships, taking different aspects of the exceedingly complex systems into account. To this end model systems using metal particles supported on well ordered thin oxide films of appropriate thickness, which allow investigations with the rigor of modern surface science while grasping essential aspects of the complexity of real systems, have proven to give valuable insight into the details of geometric and electronic structure, as well as adsorption and reaction properties [2–6]. It has been recognized that the thickness of the oxide films, as they are grown on metal substrates, may be used as a design principle to create materials of potential in catalysis. A concept to control the catalytic activity of a dispersed metal by the thickness of an insulating oxide layer was introduced some 20 years ago by Cogen et al. using silica layers covering Pt [7]. In this case the catalytic performance for dehydrogenation of cycloalkenes depends significantly on the thickness of the silica films, which was explained by the decreasing transport of hydrogen atoms produced at the Pt surface through the silica film. The main experimental challenge, however, is to provide undisputable prove for the proposed mechanisms which is usually hampered either by the complexity of the samples investigated and/or the lack of appropriate methodology to exclude interference with alternative mechanisms. Having ultimate control, as available today, over the thickness and structure of the oxide films, these properties may be used to control the charge state and, thus, the catalytic properties of a metal deposited onto them, an idea related to those proposed by Cabrera and

Unexpected impacts of climate change on alpine vegetation

Abstract: The vegetation in a high alpine site of the European Alps experienced changes in area between 1953 and 2003 as a result of climate change. Shrubs showed rapid expansion rates of 5.6% per decade at altitudes between 2400 m and 2500 m. Above 2500 m, vegetation coverage exhibited unexpected patterns of regression associated with increased precipitation and permafrost degradation. As these changes follow a sharp increase in both summer and annual temperatures after 1980, we suggest that vegetation of the alpine (2400–2800 m) and nival (above 2800 m) belts respond in a fast and flexible way, contradicting previous hypotheses that alpine and nival species appear to have a natural inertia and are able to tolerate an increase of 1–2°C in mean air temperature.

GRB Radiative Efficiencies Derived from the Swift Data: GRBs versus XRFs, Long versus Short

Abstract: We systematically analyze the prompt emission and the early afterglow data of a sample of 31 GRBs detected by Swift before 2005 September and estimate the GRB radiative efficiency. BAT's narrow band inhibits a precise determination of the GRB spectral parameters, and we have developed a method to estimate these parameters with the hardness ratio information. The shallow decay component commonly existing in early X-ray afterglows, if interpreted as continuous energy injection in the external shock, suggests that the GRB efficiencies previously derived from the late-time X-ray data were not reliable. We calculate two radiative efficiencies using the afterglow kinetic energy E(K) derived at the putative deceleration time (t(dec)) and at the break time (t(b)), when the energy injection phase ends, respectively. At tb XRFs appear to be less efficient than normal GRBs. However, when we analyze the data at tdec, XRFs are found to be as efficient as GRBs. Short GRBs have similar radiative efficiencies to long GRBs despite of their different progenitors. Twenty-two bursts in the sample are identified to have the afterglow cooling frequency below the X-ray band. Assuming epsilon(e) 0:1, we find eta(gamma)(t(b)) usually 90%. Nine GRBs in the sample have the afterglow cooling frequency above the X-ray band for a very long time. This suggests a very small epsilon(B) and/or a very low ambient density n.

Comparative analysis of alcohol control policies in 30 countries.

Abstract: Background Alcohol consumption causes an estimated 4% of the global disease burden, prompting goverments to impose regulations to mitigate the adverse effects of alcohol. To assist public health leaders and policymakers, the authors developed a composite indicator—the Alcohol Policy Index—to gauge the strength of a country's alcohol control policies. Methods and Findings The Index generates a score based on policies from five regulatory domains—physical availability of alcohol, drinking context, alcohol prices, alcohol advertising, and operation of motor vehicles. The Index was applied to the 30 countries that compose the Organization for Economic Cooperation and Development and regression analysis was used to examine the relationship between policy score and per capita alcohol consumption. Countries attained a median score of 42.4 of a possible 100 points, ranging from 14.5 (Luxembourg) to 67.3 (Norway). The analysis revealed a strong negative correlation between score and consumption (r ¼� 0.57; p ¼0.001): a 10-point increase in the score was associated with a one-liter decrease in absolute alcohol consumption per person per year (95% confidence interval, 0.4-1.5 l). A sensitivity analysis demonstrated the robustness of the Index by showing that countries' scores and ranks remained relatively stable in response to variations in methodological assumptions.

Intraoperative subcortical language tract mapping guides surgical removal of gliomas involving speech areas.

Abstract: Objective Subcortical stimulation can be used to identify functional language tracts during resection of gliomas located close to or within language areas or pathways. The objective of the present study was to investigate the feasibility of the routine use of subcortical stimulation for identification of language tracts in a large series of patients with gliomas and to determine the influence that subcortical language tract identification exerted on the extent of surgery and on the appearance of immediate and definitive postoperative deficits. Methods Subcortical stimulation for language tract identification was systematically used during surgical removal of 88 gliomas (44 high-grade and 44 low-grade gliomas) involving language pathways. Procedures were performed during asleep/awake craniotomy. Subcortical stimulation was continuously alternated with surgical resection in a back-and-forth fashion. Language performances were tested by neuropsychological language evaluation preoperatively and at 3, 30, and 90 days after surgery. Results Language tracts were identified in 59% of patients, with differences according to tumor location but not according to histological grade. Language tract identification influenced the ability to reach a complete tumor removal in low-grade gliomas, in which tracts were documented inside the peripheral mass of the tumor. Identification of language tracts was associated with a higher occurrence of transient postoperative deficits (67.3% of cases), but a low occurrence of definitive morbidity (2.3% of cases). A pattern of typical language disturbances related to the phonological and semantic system can be identified according to tumor location, with preservation being important for the maintenance of language integrity. Conclusion Our study supports the routine use of subcortical stimulation for language tract identification as a reliable tool for guiding surgical removal of gliomas in or in close proximity to language areas or pathways.

Trends in oesophageal cancer incidence and mortality in Europe.

Abstract: To monitor recent trends in mortality from oesophageal cancer in 33 European countries, we analyzed the data provided by the World Health Organization over the last 2 decades, using also joinpoint regression. For selected European cancer registration areas, we also analyzed incidence rates for different histological types. For men in the European Union (EU), age-standardized (world population) mortality rates were stable around 6/100,000 between the early 1980s and the early 1990s, and slightly declined in the last decade (5.4/100,000 in the early 2000s, annual percent change, APC = −1.1%). In several western European countries, male rates have started to level off or decline during the last decade (APC = −3.4% in France, and −3.0% in Italy). Also in Spain and the UK, which showed upward trends in the 1990s, the rates tended to level off in most recent years. A levelling of rates was observed only more recently in countries of central and eastern Europe, which had had substantial rises up to the late 1990s. Oesophageal cancer mortality rates remained comparatively low in European women, and overall EU female rates were stable around 1.1–1.2/100,000 over the last 2 decades (APC = −0.1%). In northern Europe a clear upward trend was observed in the incidence of oesophageal adenocarcinoma, and in Denmark and Scotland incidence of adenocarcinoma in men is now higher than that of squamous-cell carcinoma. Squamous-cell carcinoma remained the prevalent histological type in southern Europe. Changes in smoking habits and alcohol drinking for men, and perhaps nutrition, diet and physical activity for both sexes, can partly or largely explain these trends. © 2007 Wiley-Liss, Inc.

Metabolic Syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) Study: Daily Life Blood Pressure, Cardiac Damage, and Prognosis

Abstract: The prevalence of the metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III criteria) and its relationships with daily life blood pressures, cardiac damage, and prognosis were determined in 2013 subjects from a Northern Italian population aged 25 to 74 years. Home blood pressure, 24-hour blood pressure, and left ventricular mass index (echocardiography) were also measured. Cardiovascular and noncardiovascular deaths were registered over 148 months. Metabolic syndrome was found in 16.2% of the sample, an office blood pressure elevation being the most frequent (95.4%) and the blood glucose abnormality the least frequent (31.5%) component. There was in metabolic syndrome a frequent elevation in home and/or 24-hour average blood pressure, as well as a greater left ventricular mass index and prevalence of left ventricular hypertrophy, which was manifest even when data were adjusted for between-group differences, including blood pressure. The adjusted risk of cardiovascular and all-cause mortality was greater in metabolic syndrome subjects (+71.0% and +37.0%; P<0.05), a further marked increase being observed with left ventricular hypertrophy or "in-office" and "out-of-office" blood pressure elevations. The increased risk was related to the blood pressure and the blood glucose component of metabolic syndrome, with no contribution of the remaining components. Thus, metabolic syndrome is common in a Mediterranean population in which it significantly increases the long-term risk of death. Cardiac abnormalities and increases in home and 24-hour blood pressure are common in metabolic syndrome, and their occurrence further enhances the risk. The contribution of metabolic syndrome components to the risk, however, is unbalanced and mainly related to blood pressure and glucose abnormalities.

Population trends of widespread woodland birds in Europe

Abstract: We explore population trends of widespread and common woodland birds using data from an extensive European network of ornithologists for the period 1980–2003. We show considerable differences exist in the European trends of species according to the broad habitat they occupy and the degree to which they specialize in habitat use. On average, common forest birds are in shallow decline at a European scale; common forest birds declined by 13%, and common forest specialists by 18%, from 1980 to 2003. In comparison, populations of common specialists of farmland have declined moderately, falling on average by 28% from 1980 to 2003. These patterns contrast with that shown by generalist species whose populations have been roughly stable over the same period, their overall index increasing by 3%. There was some evidence of regional variation in the population trends of these common forest species. The most obvious pattern was the greater stability of population trends in Eastern Europe compared with other regions considered. Among common forest birds, long-distance migrants and residents have on average declined most strongly, whereas short-distance migrants have been largely stable, or have increased. There was some evidence to suggest that ground- or low-nesting species have declined more strongly on average, as have forest birds with invertebrate diets. Formal analysis of the species trends confirmed the influence of habitat use, habitat specialization and nest-site; the effects of region and migration strategy were less clear-cut. There was also evidence to show that year-to-year variation in individual species trends at a European scale was influenced by cold winter weather in a small number of species. We recommend that the species trend information provided by the new pan-European scheme should be used alongside existing mechanisms to review the conservation status of European birds. The analysis also allows us to reappraise the role of common forest bird populations as a potential barometer of wider forest health. The new indicator appears to be a useful indicator of the state of widespread European forest birds and might prove to be a useful surrogate for trends in forest biodiversity and forest health, but more work is likely to be needed to understand the interaction between bird populations and their drivers in forest.

Duodenal levodopa infusion for advanced Parkinson's disease: 12‐month treatment outcome

Abstract: We assessed prospectively clinical and quality of life changes in 9 patients with Parkinson's disease (PD; HY P < 0.05). Two patients withdrew for adverse events. Our results demonstrate that a satisfactory therapeutic window can be achieved and maintained for several months in advanced PD patients. © 2007 Movement Disorder Society

Bcr-Abl stabilizes β-catenin in chronic myeloid leukemia through its tyrosine phosphorylation

Abstract: Self-renewal of Bcr-Abl+ chronic myeloid leukemia (CML) cells is sustained by a nuclear activated serine/threonine-(S/T) unphosphorylated β-catenin. Although β-catenin can be tyrosine (Y)-phosphorylated, the occurrence and biological relevance of this covalent modification in Bcr-Abl-associated leukemogenesis is unknown. Here we show that Bcr-Abl levels control the degree of β-catenin protein stabilization by affecting its Y/S/T-phospho content in CML cells. Bcr-Abl physically interacts with β-catenin, and its oncogenic tyrosine kinase activity is required to phosphorylate β-catenin at Y86 and Y654 residues. This Y-phospho β-catenin binds to the TCF4 transcription factor, thus representing a transcriptionally active pool. Imatinib, a Bcr-Abl antagonist, impairs the β-catenin/TCF-related transcription causing a rapid cytosolic retention of Y-unphosphorylated β-catenin, which presents an increased binding affinity for the Axin/GSK3β complex. Although Bcr-Abl does not affect GSK3β autophosphorylation, it prevents, through its effect on β-catenin Y phosphorylation, Axin/GSK3β binding to β-catenin and its subsequent S/T phosphorylation. Silencing of β-catenin by small interfering RNA inhibited proliferation and clonogenicity of Bcr-Abl+ CML cells, in synergism with Imatinib. These findings indicate the Bcr-Abl triggered Y phosphorylation of β-catenin as a new mechanism responsible for its protein stabilization and nuclear signalling activation in CML.

Sleep apnea: epidemiology, pathophysiology, and relation to cardiovascular risk

Abstract: Several studies have shown the occurrence of an independent association between obstructive sleep apnea syndrome (OSAS) and cardiovascular disease, including arterial hypertension, ischemic heart disease, and stroke. The pathogenesis of the cardiovascular complications of OSAS is still poorly understood, however. Several mechanisms are likely to be involved, including sympathetic overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormality in the process of coagulation, and metabolic dysregulation. The latter may involve insulin resistance and disorders of lipid metabolism. The aim of this review, which reports the data presented at a workshop jointly endorsed by the European Society of Hypertension and by the European Union COST action on OSAS (COST B26), is to critically summarize the evidence available to support an independent association between OSAS and cardiovascular disease.

A new method for assessing 24-h blood pressure variability after excluding the contribution of nocturnal blood pressure fall

Abstract: ObjectivesTo assess quantitatively the relationship between nocturnal blood pressure (BP) fall and 24-h BP variability; to propose a new method for computing 24-h BP variability, devoid of the contribution from nocturnal BP fall; and to verify the clinical value of this method.Methods and resultsWe

A Model-Based Deconvolution Approach to Solve Fiber Crossing in Diffusion-Weighted MR Imaging

Abstract: A deconvolution approach is presented to solve fiber crossing in diffusion magnetic resonance imaging. In order to provide a direct physical interpretation of the signal generation process, we started from the classical multicompartment model and rewrote this in terms of a convolution process, identifying a significant scalar parameter alpha to characterize the physical system response. Deconvolution is performed by a modified version of the Richardson-Lucy algorithm. Simulations show the ability of this method to correctly separate fiber crossing, even in the presence of noisy data, with lower signal-to-noise ratio, and imprecision in the impulse response function imposed during deconvolution. The in vivo data confirms the efficacy of this method to resolve fiber crossing in real complex brain structures. These results suggest the usefulness of our approach in fiber tracking or connectivity studies

Rigorous Derivation of the Cubic NLS in Dimension One

Abstract: We derive rigorously the one-dimensional cubic nonlinear Schrodinger equation from a many-body quantum dynamics. The interaction potential is rescaled through a weak-coupling limit together with a short-range one. We start from a factorized initial state, and prove propagation of chaos with the usual two-step procedure: in the former step, convergence of the solution of the BBGKY hierarchy associated to the many-body quantum system to a solution of the BBGKY hierarchy obtained from the cubic NLS by factorization is proven; in the latter, we show the uniqueness for the solution of the infinite BBGKY hierarchy.

Blood Pressure Control and Improved Cardiovascular Outcomes in the International Verapamil SR-Trandolapril Study

Abstract: Uncontrolled blood pressure (BP) increases cardiovascular risk, independent of type of treatment. In this posthoc International Verapamil SR-Trandolapril Study analysis, we determined whether adverse outcomes are related to consistency of BP control, defined as the proportion of visits in which BP was in control. A total of 22 576 patients with hypertension and coronary artery disease were divided into 4 groups according to the proportion of visits in which BP was in control ( or=75%. Risk of primary outcome (first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke), myocardial infarction, and stroke decreased progressively from the group with or=75% of visits with BP control. Adjusted risks of primary outcome (heart rate: 0.60; 95% CI: 0.53 to 0.67), myocardial infarction (heart rate: 0.58; 95% CI: 0.48 to 0.70), and stroke (heart rate: 0.50; 95% CI: 0.37 to 0.67) were less in the group with >or=75% of visits with BP control compared with the group with <25% of visits with BP control. Baseline BP was not predictive of outcomes. Proportion of visits with BP control was associated with mean follow-up systolic BP (r(2)=0.64), both being independently related to primary outcome. As proportion of visits with BP control increases, there is an associated steep reduction in cardiovascular risk, independent of baseline characteristics and mean on-treatment BP. Consistency of BP control during treatment provides additional information on the protective effect of antihypertensive treatment. Physicians need to be concerned at each visit if BP is not controlled.

Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy

Abstract: Duchenne muscular dystrophy is a relatively common disease that affects skeletal muscle, leading to progressive paralysis and death. There is currently no resolutive therapy. We have developed a treatment in which we combined the effects of nitric oxide with nonsteroidal antiinflammatory activity by using HCT 1026, a nitric oxide-releasing derivative of flurbiprofen. Here, we report the results of long-term (1-year) oral treatment with HCT 1026 of two murine models for limb girdle and Duchenne muscular dystrophies (α-sarcoglycan-null and mdx mice). In both models, HCT 1026 significantly ameliorated the morphological, biochemical, and functional phenotype in the absence of secondary effects, efficiently slowing down disease progression. HCT 1026 acted by reducing inflammation, preventing muscle damage, and preserving the number and function of satellite cells. HCT 1026 was significantly more effective than the corticosteroid prednisolone, which was analyzed in parallel. As an additional beneficial effect, HCT 1026 enhanced the therapeutic efficacy of arterially delivered donor stem cells, by increasing 4-fold their ability to migrate and reconstitute muscle fibers. The therapeutic strategy we propose is not selective for a subset of mutations; it provides ground for immediate clinical experimentation with HCT 1026 alone, which is approved for use in humans; and it sets the stage for combined therapies with donor or autologous, genetically corrected stem cells.