Paradigm Switch Research Articles

Topology optimization-driven design of added rib architecture system for enhanced free vibration response of thin-wall plastic components used in the automotive industry

A relentless paradigm switch in the automotive industry is being witnessed, where traditional combustion engines are progressively replacing with electric counterparts. In order to compensate for heavy electric engine technology, plastic components used in the interior parts of electric vehicles seems to be a reasonable strategy aligned with the lightweight trend as the automotive industry’s top priority. Extremely thin plastic components (ultra-lightweight) attached to ribs-based architectures have been identified as an adequate solution offering a good balance between lightweight and structural/vibrational response of the overall composition. Still, they may yield detrimental features regarding thermal-induced deformations (i.e., warpage and shrinkage) associated with the typical mold injection process for their manufacturing. This paper uses topology optimization to determine the precise location of the added rib architecture system for enhanced vibration response of the overall plastic component (thin original plastic part and ribs architecture). Following a constant mass criterion, the topology optimization-driven design of the additional material is replaced with a more convenient ribs-based architecture component, showing a reasonable similarity from a vibration standpoint. The component in its initial state (without some ribs-based architecture) shows a vibration response of 16.69 Hz. Once the topology optimization is applied, a significant improvement is observed since a value of 26.05 Hz is obtained. At a postprocessing stage, the design is analyzed and subjected to typical static loading cases to verify its stiffness properties, getting a significant displacement reduction from 7.68 to 3.51 mm. Finally, the design implementation of a warpage and shrinkage analysis confirmed that the final design was not adversely affected according to standard considerations.

Evolution of a Paradigm Switch in Diagnosis and Treatment of HPV-Driven Head and Neck Cancer-Striking the Balance Between Toxicity and Cure.

More than a decade after the discovery of p16 immunohistochemistry (IHC) as a surrogate for human papilloma virus (HPV)-driven head and neck squamous cell carcinoma (HNSCC), p16-IHC has become a routinely evaluated biomarker to stratify oropharyngeal squamous cell carcinoma (OPSCC) into a molecularly distinct subtype with favorable clinical prognosis. Clinical trials of treatment de-escalation frequently use combinations of biomarkers (p16-IHC, HPV-RNA in situ hybridization, and amplification of HPV-DNA by PCR) to further improve molecular stratification. Implementation of these methods into clinical routine may be limited in the case of RNA by the low RNA quality of formalin-fixed paraffin-embedded tissue blocks (FFPE) or in the case of DNA by cross contamination with HPV-DNA and false PCR amplification errors. Advanced technological developments such as investigation of tumor mutational landscape (NGS), liquid-biopsies (LBx and cell-free cfDNA), and other blood-based HPV immunity surrogates (antibodies in serum) may provide novel venues to further improve diagnostic uncertainties. Moreover, the value of HPV/p16-IHC outside the oropharynx in HNSCC patients needs to be clarified. With regards to therapy, postoperative (adjuvant) or definitive (primary) radiochemotherapy constitutes cornerstones for curative treatment of HNSCC. Side effects of chemotherapy such as bone-marrow suppression could lead to radiotherapy interruption and may compromise the therapy outcome. Therefore, reduction of chemotherapy or its replacement with targeted anticancer agents holds the promise to further optimize the toxicity profile of systemic treatment. Modern radiotherapy gradually adapts the dose. Higher doses are administered to the visible tumor bulk and positive lymph nodes, while a lower dose is prescribed to locoregional volumes empirically suspected to be invaded by tumor cells. Further attempts for radiotherapy de-escalation may improve acute toxicities, for example, the rates for dysphagia and feeding tube requirement, or ameliorate late toxicities like tissue scars (fibrosis) or dry mouth. The main objective of current de-intensification trials is therefore to reduce acute and/or late treatment-associated toxicity while preserving the favorable clinical outcomes. Deep molecular characterization of HPV-driven HNSCC and radiotherapy interactions with the tumor immune microenvironment may be instructive for the development of next-generation de-escalation strategies.

Thyroid testing paradigm switch from thyrotropin to thyroid hormones\u2014Future directions and opportunities in clinical medicine and research

PurposeRecently published papers have demonstrated that particularly in untreated individuals, clinical parameters more often associate with thyroid hormone, particularly free thyroxine (FT4), levels than with thyrotropin (TSH) levels. Clinical and research assessments of the thyroid state of peripheral tissues would therefore be more precise if they were based on FT4 levels rather than on TSH levels. In this paper we describe implications of, and opportunities provided by, this discovery.ConclusionsThe FT4 level may be the best single test of thyroid function. The addition of free triiodothyronine (FT3) and TSH levels would further enhance test sensitivity and distinguish primary from secondary thyroid dysfunction respectively. There are opportunities to reconsider testing algorithms. Additional potential thyroidology research subjects include the peripheral differences between circulating FT4 and FT3 action, and outcomes in patients on thyroid replacement therapy in terms of thyroid hormone levels. Previously performed negative studies of therapy for subclinical thyroid dysfunction could be repeated using thyroid hormone levels rather than TSH levels for subject selection and the monitoring of treatment. Studies of outcomes in older individuals with treatment of high normal FT4 levels, and pregnant women with borderline high or low FT4 levels would appear to be the most likely to show positive results. There are fresh indications to critically re-analyse the physiological rationale for the current preference for TSH levels in the assessment of the thyroid state of the peripheral tissues. There may be opportunities to apply these research principles to analogous parameters in other endocrine systems.

The Challenges of Hospitals' Planning & Control Systems: The Path toward Public Value Management.

In the last decades, public management has been subjected to a shift from the New Public Management (NPM) paradigm to the Public Value Management (PVM) one. Thus, management practices such as Planning and Control (P&C) systems have been called to evolve accordingly. The health care sector has not escaped this process. This paper focuses on the evolution of hospitals’ P&C systems to support the paradigm shift from the NPM paradigm to the PVM one. In particular, the paper aims at exploring whether hospitals’ P&C systems in Italy evolved, or are evolving, consistently with PVM and what are the expected benefits related to such a paradigm switch. To address the research aim, the paper is based on a review of scientific and grey literature and the case study of the diabetic-foot pathway in an Italian Regional Healthcare System. The results of this study show that the current P&C systems in Italian hospitals are not yet designed to support the shift toward the PVM approach and are still mainly focused on financial aspects and intra-organizational dynamics. Combining traditional P&Cs with performance measures assessing the system’s outcomes may support hospitals in aligning their goals with the health system they are operating within and, therefore, P&C systems may represent an important driving force toward change. Such results provide suggestions for both practitioners and academics on how to adapt P&C systems to better support the implementation of current strategies of the public sector.

Visual Literacy Intervention for Improving Undergraduate Student Critical Thinking of Global Sustainability Issues

The promotion of global sustainability within environmental science courses requires a paradigm switch from knowledge-based teaching to teaching that stimulates higher-order cognitive skills. Non-major undergraduate science courses, such as environmental science, promote critical thinking in students in order to improve the uptake of scientific information and develop the rational decision making used to make more informed decisions. Science, engineering, technology and mathematics (STEM) courses rely extensively on visuals in lectures, readings and homework to improve knowledge. However, undergraduate students do not automatically acquire visual literacy and a lack of intervention from instructors could be limiting academic success. In this study, a visual literacy intervention was developed and tested in the face-to-face (FTF) and online sections of an undergraduate non-major Introduction to Environmental Science course. The intervention was designed to test and improve visual literacy at three levels: (1) elementary—identifying values; (2) intermediate—identifying trends; and (3) advanced—using the data to make projections or conclusions. Students demonstrated a significant difference in their ability to answer elementary and advanced visual literacy questions in both course sections in the pre-test and post-test. Students in the face-to-face course had significantly higher exam scores and higher median assessment scores compared to sections without a visual literacy intervention. The online section did not show significant improvements in visual literacy or academic success due to a lack of reinforcement of visual literacy following the initial intervention. The visual literacy intervention shows promising results in improving student academic success and should be considered for implementation in other general education STEM courses.

“Oil is the New Data”: Energy Technology Innovation in Digital Oil Fields

Digital oil fields (DOFs) are built on data produced from energy technology innovation during the application of new technologies to oil resource development. In this study, this conversion is examined through the paradigm switch to “oil is the new data”. An analysis of related patents shows that DOF technology is developing through convergence and close links with other industries, specifically the equipment, parts, and material industries. Additionally, it is conjectured that the strategic preemption of standards will emerge as an important policy issue because a standard must be established for the interoperability of the elemental technologies of DOFs. Furthermore, with the expansion of DOF-related technologies, device-related technologies have also been developed. Of these device-related technologies, sensor technology specifically provides new possibilities for the development of DOFs. The significance of this study is that it explains the evolution of DOFs over the course of 10 years, which is illustrative of technological innovation in the field of energy-related development and data collection.

The new public health imposed and its missing links - people, cultures, anthropology, health for all

Critical medical anthropology has been active throughout the decades (Baer, Susser, Singer 1986; Lock, Nichter, 2002; Lupton, 1995. 2000, 2015) in proving that public health is not only an addition to equations of equity in health care but rooted in cultures of people globally (Špoljar Vržina 2003, 2007, 2008; 2011, 2013, 2021; Špoljar Vržina, Rudan, 2009). Italian anthropologist codified the postmodern 'doing good only in states of emergencies' (Pandolfi, 2010). In times of Corona Covid 19 -2020 epidemiological freights we are urged to take this further into account, especially since witnessing racial stigmatizing on the basis of ethnicity and nationality. Paradoxically, Italy as one of the cradles of quarantines is facing the potential permanent closure of neighbouring borders rather than experiencing a historically practiced cooperation, as in the case with Croatia, over centuries (Blažina, Blažina 2015). If there should be a New Public Health (Baum 2016, 2019; Lupton 1997, 2000) it should be recalibrated by anthropological findings that re- focus towards the good of people, cultures and their cooperation. The work of this paper presents this urgent challenge. This anthropological research is a long-term follow up of Croatian medicine system dismantling (Špoljar Vržina, 2008 onwards) through a continuous analyses of micro (people), intermediary (governmental) and macro (international) changes (Bear et al. 1986), departures from functioning for the benefit of people and finding entry points for ethical corrective interventions. The analysis proved an existing switch of the public health paradigm from global health into states of neoliberal sickness, with clear possibilities of returning to 'health for all' if disengaging from the politics of culture/public health. Public health enhancements need to be based on the recalibration towards knowledges of populational and cultural realities.Key messages Reintroducing the ‘innovative’ wisdom of doing good for all regardless of emergencies is the core of a new public health agenda.The new public health agenda is based on recognizing cultures as pillars of communities and global societies that matter.

The Paradigm of Reciprocity: How to Radically Respect Spontaneity in Clinical Practice

AbstractThis article explores how the concept of radical respect, crucial in Gestalt therapy, has changed over the years. Novel contemporary social situations challenge our organism/environment balance and call for new professional values. Today, clinical sufferings (i.e., desensitization, fragile sense of self, increase in impulsive behaviors) require that Gestalt therapists focus on the support of the ground experience rather than the figure. Examples of how to work on the ground are given, along with research results. The author then proposes a switch of paradigm in psychotherapy: to support the reciprocity and its dance in meaningful contacts. The aesthetic relational knowledge of the field is described as a new tool through which the therapist may draw upon her resonance in the field.

Deciphering host immunity to malaria using systems immunology.

A century of conceptual and technological advances in infectious disease research has changed the face of medicine. However, there remains a lack of effective interventions and a poor understanding of host immunity to the most significant and complex pathogens, including malaria. The development of successful interventions against such intractable diseases requires a comprehensive understanding of host-pathogen immune responses. A major advance of the past decade has been a paradigm switch in thinking from the contemporary reductionist (gene-by-gene or protein-by-protein) view to a more holistic (whole organism) view. Also, a recognition that host-pathogen immunity is composed of complex, dynamic interactions of cellular and molecular components and networks that cannot be represented by any individual component in isolation. Systems immunology integrates the field of immunology with omics technologies and computational sciences to comprehensively interrogate the immune response at a systems level. Herein, we describe the system immunology toolkit and report recent studies deploying systems-level approaches in the context of natural exposure to malaria or controlled human malaria infection. We contribute our perspective on the potential of systems immunity for the rational design and development of effective interventions to improve global public health.

Credit Valuation Adjustment Compression by Genetic Optimization

Since the 2008–2009 financial crisis, banks have introduced a family of X-valuation adjustments (XVAs) to quantify the cost of counterparty risk and of its capital and funding implications. XVAs represent a switch of paradigm in derivative management, from hedging to balance sheet optimization. They reflect market inefficiencies that should be compressed as much as possible. In this work, we present a genetic algorithm applied to the compression of credit valuation adjustment (CVA), the expected cost of client defaults to a bank. The design of the algorithm is fine-tuned to the hybrid structure, both discrete and continuous parameter, of the corresponding high-dimensional and nonconvex optimization problem. To make intensive trade incremental XVA computations practical in real-time as required for XVA compression purposes, we propose an approach that circumvents portfolio revaluation at the cost of disk memory, storing the portfolio exposure of the night so that the exposure of the portfolio augmented by a new deal can be obtained at the cost of computing the exposure of the new deal only. This is illustrated by a CVA compression case study on real swap portfolios.

Envisioning data sharing for the biocomputing community.

The scientific community is facing a revolution in several aspects of its modus operandi, ranging from the way science is done-data production, collection, analysis-to the way it is communicated and made available to the public, be that an academic audience or a general one. These changes have been largely determined by two key players: the big data revolution or, less triumphantly, the impressive increase in computational power and data storage capacity; and the accelerating paradigm switch in science publication, with people and policies increasingly pushing towards open access frameworks. All these factors prompt the undertaking of initiatives oriented to maximize the effectiveness of the computational efforts carried out worldwide. Taking the moves from these observations, we here propose a coordinated initiative, focusing on the computational biophysics and biochemistry community but general and flexible in its defining characteristics, which aims at addressing the growing necessity of collecting, rationalizing, sharing and exploiting the data produced in this scientific environment.

Myositis-specific autoantibodies, a cornerstone in immune-mediated necrotizing myopathy.

Over the past few years, myositis-specific autoantibodies played an increasing role in the inflammatory idiopathic myositis definition. They became the critical immunological marker for immune-mediated necrotizing myopathy diagnosis (IMNM) since the paradigm switch from histological to serological criteria. This review is focused on the key role of the anti-signal recognition particle (anti-SRP) and the anti-3-Hydroxy-3-MethylGlutaryl-Coenzyme A Reductase (anti-HMGCR) antibodies in immune-mediated necrotizing myopathy. Anti-SRP and anti-HMGCR antibodies are robust diagnostic tools in case of both the classical subacute form and the slowly progressive form of IMNM that may mimic muscular dystrophy. Anti-SRP and anti-HMGCR patients share clinical, biological and histological features with some antibody-associated specificity. Anti-SRP patients harbour more severe muscle weakness and atrophy with severe muscle damage on magnetic resonance imaging study. Approximately 10-20% of anti-SRP patients develop extramuscular symptoms, especially lung interstitial disease. Conversely, anti-HMGCR patients are often associated with statin exposure. In both cases, patients have a poor outcome with frequent relapse and the use of combined immunotherapy. Of note, various data suggest a direct pathogenic role of these antibodies reinforcing the interest in targeted therapeutic strategy.

ORPHEUS: THE SYMBOL OF A NEW MUSIC ERA

The purpose of the article is to analyse the philosophical and aesthetical processes, which at the beginning of Modern Times had led to the formation of new musical-aesthetical paradigm, thereby changing the world of music and resulting in creating of the emotionally colored music as we know it. This belated Renaissance in music is inextricably linked to the emergence of opera and to the reconstructions of the antique musical-aesthetical philosophical ideas, attitudes and values in Northern Italy at the end of the 16th and beginning of the 17th century. One of the first scholars who appealed to the long-abandoned ancient Greek philosophical doctrine of ethos was Nicola Vicentino (1511-1572). In his magnum opus L’antica musica ridotta alla moderna prattica (1555) he insisted that music should be connected to the lyrics (i.e. to the passions and ideas contained in it). The same position defended Girolamo Mei (1519-1594), who clearly states on it in his multiple letters to Vincenzo Galilei (1520-1591). Vincenzo Galilei, in turn, was the mastermind and inspirer of famous Florentine Camerata (also known as Camerata de’ Bardi) – the club of thinkers, poets and composers, which was founded in 1573 in order to put into practice ancient Greek musical aesthetical principles. The most famous members of Camerata – Giulio Caccini, Jacopo Peri, Vincenzo Galilei, Giovanni Battista Doni, Ottavio Rinuccini, Piero Strozzi. Of course, the most visible result of the activity of Camerata was creating the first works of dramma per musica – “Dafne” (1598), “Euridice” (1600) by Jacopo Peri and “Euridice” (1602) by Giulio Caccini. But the most important and widely disseminated at the time experimenting in the field of new musical art was concentrated in the genre of madrigal. Due to such activity at the late XVI – early XVII centuries arises new musical-aesthetical paradigm, which on the external level has revealed itself in emerging of the new, mostly homophonic representative stile (stile rappresentativo) as opposition to the old polyphonic stile (stile antico, stile grave, stile osservato). In this new representative style musical content is subordinate to lyrics. Most clearly the switch of musical-aesthetical paradigm was manifested in the MonteverdiArtusi controversy between the greatest composer of the time Claudio Monteverdi and the scholar Giovanni Artusi, who was criticizing new music. Monteverdi, as an apologist of a new musicalaesthetical principles described his famous concept of Seconda pratica (the Second Practice) in the following texts: Afterword for the 5th Book of Madrigals (1605), Forward for the 8th Book of Madrigals, The Letters to Unknown, 22 October 1633 and 2 February 1634. But the most complete statement of his ideas can be found in Dichiarazione of his brother Giulio Monteverdi, which was published in the collection of pieces Scherzi musicali by Claudio Monteverdi (1607). As the result of such philosophical and practical activity at the late XVI – early XVII centuries, the emotionally neutral consonant church polyphony was replaced by new affective musical material based not on the perfect ratios and proportions, but on the affect as a reflection of the human nature. The article focused on the reflection of this transitional period in the history of music, which conditionally ends with the creation of the first-ever true musical drama – “L’Orfeo” by Claudio Monteverdi (1607).

Growing Old and Keep Mobile in Italy. Active Ageing and the Importance of Urban Mobility Planning Strategies.

The world is facing a series of changes that will modify the way we envisage urban transport planning. The demographic switch coupling higher life expectancy and lower fertility rates is occurring all around the world. While ageing is indeed a triumph of development and increased longevity is perceived as one of humanity’s greatest achievements, the phenomenon and its transition in society need to be managed. The rapid increase of the elderly group means profound changes which require solutions at various levels. The World Health Organization has established a path towards Active ageing, and it is within this strategy that this paper aims at analyzing the role of mobility as an enabler of active ageing. While mobility in general is very important, it was decided to concentrate on urban mobility, as cities are, by definition, the place where people benefit from urbanization economies and where transport plans are put in place. An increase of age, health and economic conditions determine the possibility to enjoy urbanization economics more and for longer time. Yet such fruition is determined by the accessibility to such places or services. It is for this reason, among others, that urban mobility planning is such a relevant tool that could lead towards a switch of paradigm towards more friendly and inclusive (for seniors and not only) urban environments.

Targeting One-Hour Postmeal Glucose: Is It Time for a Paradigm Switch in Diabetes Management?

In the management of diabetes, postprandial glycemia (PPG) is usually targeted 2 h after the start of meal. Recent evidences, however, suggest that the value of glycemia at 1 h during an oral glucose tolerance test (OGTT) is a stronger predictor for developing diabetes than the value at 2 h and that it is an independent risk factor for cardiovascular disease. Studies in cells, animals, and humans suggest that 1-h high glucose is a sufficient stimulus for increasing several cardiovascular risk factors, such as inflammation, thrombosis, and endothelial dysfunction, with oxidative stress generation as the possible pathogenetic factor. One-hour glucose might be more dangerous than that at 2 h simply because glycemia is higher at 1 h, during an OGTT and postmeal. The new drugs, able to target better 1 h glycemia and the new noninvasive technologies for glucose monitoring, nowadays may help to change the therapeutic paradigm of targeting PPG at 2 h.

Functional neuro-imaging with magnetic resonance elastography

Evaluate changes in the shear modulus of brain tissue as a new measure of localized brain function. A spin-echo magnetic resonance elastography (MRE) sequence was modified to allow two interleaved paradigms: stimulus ON/OFF. To avoid neuronal habituation, a paradigm was active for 9s before switching to the other paradigm. After each paradigm switch, a period of 1.8 s was allowed for hemodynamic equilibrium. Seven healthy black mice were studied. An electrical current to the hind limb, ~1 mA, 3 Hz, pulse width ~250 ms, was used as the functional stimulus. A separate control scan was also performed where no stimulus was applied for either paradigm. Vibration frequency = 1kHz. In six of the seven animals, a localized increase in G’ was observed in the somatosensory and motor cortex areas, whereas no difference was observed in the control scan. The average increase of G’ = 14%. Two potential mechanisms were considered: (i) a vascular effect similar to BOLD in fMRI and (ii) calcium influx into the neurons. The first mechanism was ruled out based on results from an additional experiment where hypercapnia was induced to cause vasodilation. This implies the mechanism responsible is a primary measure of neuronal activation.

Asymptotic theory of time varying networks with burstiness and heterogeneous activation patterns

The recent availability of large-scale, time-resolved and high quality digital datasets has allowed for a deeper understanding of the structure and properties of many real-world networks. The empirical evidence of a temporal dimension prompted the switch of paradigm from a static representation of networks to a time varying one. In this work we briefly review the framework of time-varying-networks in real world social systems, especially focusing on the activity-driven paradigm. We develop a framework that allows for the encoding of three generative mechanisms that seem to play a central role in the social networks’ evolution: the individual’s propensity to engage in social interactions, its strategy in allocate these interactions among its alters and the burstiness of interactions amongst social actors. The functional forms and probability distributions encoding these mechanisms are typically data driven. A natural question arises if different classes of strategies and burstiness distributions, with different local scale behavior and analogous asymptotics can lead to the same long time and large scale structure of the evolving networks. We consider the problem in its full generality, by investigating and solving the system dynamics in the asymptotic limit, for general classes of ties allocation mechanisms and waiting time probability distributions. We show that the asymptotic network evolution is driven by a few characteristics of these functional forms, that can be extracted from direct measurements on large datasets.

P.2.019 - Anterior cingulate cortex hypersensitivity to serotonergic challenge in migraine patients: an fMRI study

Peripheral nerve field stimulation (PNfS) is a new and exciting area of neurostimulation. It belongs to the general category of electrical stimulation of the peripheral nervous system. However, instead of stimulating a well-defined nerve trunk, the stimulation is applied to the small terminal branches of one or more peripheral nerves. The target area for the stimulation is the subcutaneous tissue, where the small nervous endings of the nerves arborize in a widespread network. The use of PNfS is a paradigm switch from previous neurostimulation modalities, where stimulation is applied to a large well-defined neural structure such as a large peripheral nerve, the nerve roots, or the spinal cord. Most common indications include intractable axial pain (lumbar, thoracic, and cervical areas), abdominal pain, and inguinal pain.The main advantages of the technique are low invasiveness, extreme selectivity of stimulation, guaranteed coverage of the painful area, and low risks and complications. PNfS can also be utilized in conjunction with spinal cord stimulation, with good synergistic and additive results. The clinical results are similar to those for other common neurostimulation modalities for chronic pain syndromes.

A new approach in Supply Chain Processes – Smart Logistics

Globalization is progressing steadily and cannot be stopped. Through existing technologies, this process will be accelerated further. Entire professions and industries, as well as government and politics, must constantly adapt to this process. Many things can be created quickly, which, in turn, creates more vulnerability. These changes are supported by different technologies, which also change rapidly, not to mention the perception of time influencing people’s awareness. Things are faster and sometimes more fragile. In this context, supply chain is perceived as a mean of expressing globalization. The present paper emphasizes the switch of paradigm from classic logistics to smart logistics. The authors analysed several prestigious reports (released by World Economic Forum, Oxford Martin Commission for Future Generations, IEEE Computer Society, etc.) to highlight the global trends in supply chain processes. The main objective of the research is to shape the near future of logistics to prepare the production and transportation industry for change.

International cooperation. Where are we, and where are we heading to?

Unmet needs in global health are important issues, not yet solved by the international community. A variety of individuals, non-governmental organizations (NGO) and government institutions have tried to address this situation, developing multiple types of international cooperation (IC), such as humanitarian aid (HA), cooperation for development (CD) and medical missions (MM). In the last decades, we have witnessed an exponential growth in the creation and participation of these projects. Moreover, in the last 20 years, Chile has experimented a real paradigm switch, from a receiver to a provider of IC. Due to the recent surge in interest and relevance of the topic, we performed a narrative revision of the literature related with IC. In the present article, we characterize the different types of IC, with emphasis in MM: we address the risks, controversies and ethical problems associated with these activities. We finally propose some guidelines for the future development and promotion of MM.