IntroductionThe addiction to heroin is a severe disorder and its treatment represents a complicated, long-lasting process, which includes a series of various interventions which have to be constantly adjusted to patients' present state and his abilities to accept the therapy. The addiction is very resistant to treatment and if the program is not at the same time, enough influential and persistent, but also acceptable to the addict to stick to it for months or even years, the expected results will not be achieved. Retention to the program, abstinence from the illicit drugs, reduction of illegal activities and improving the aspects of socially acceptable behaviour are the best indicators of therapeutic efforts [1-5].Already thirty years ago, the most of western-European countries and USA, Canada and Australia have accepted the use of methadone as a recognized method for treatment of opiate addicts and a useful tool in the frame of 'harm-reduction' approach for helping the not-motivated or incurable heroin addicts. Methadone enables those patients to stop or significantly reduce taking heroin. Although methadone does not create the feeling of euphoria similar to the effect of heroin, it replaces the biological lack of endorphins at the opioid receptors in brain and, with its help, the patient can achieve a psychophysical balance and control the pathological addict's craving. The use of methadone is the best way to attract the addicts from the street to the process of treatment and, if it is well organized and spread, can ultimately direct many addicts towards the programs that would help them in stabilizing the permanent abstinence [1-5].In the evaluation study carried out by the American National Institute for Drugs (NIDA) it has been found that the substitution therapy reduces users' heroin intake for 70%, and their criminal activity by 57 %. [6]. It has also been reported that the countries which use methadone attract up to 75% of opiate addicts to their programs, while those that do not use it, achieve less than 20 %, making the mortality of addicts due to overdose very high. A large number of addicts included in substitution programs function better socially, i.e. better fulfill their duties at the workplace and in families and display significantly less dealings with criminal activities, particularly with selling drugs, thus reducing the risk of initial drug abuse among the healthy population. Application of methadone improves the physical and mental health of the addict, his life gets longer and the risk for early sudden death is reduced. By using methadone, physical and mental health of addicts is improved, their lifespan prolonged i.e. the risk of sudden death is reduced. The addicts in substitution programs are less dangerous concerning the spread of HIV infection, hepatitis and encouraging others to take drugs. The use of methadone in pregnancy is absolutely indicated: it reduces the risk of unwanted pregnancy termination and the risk of damaging the fetus. [1]."Drug free" residential treatment of addictions in the frame of therapeutic communities (TZ) started in early sixties as groups of self and mutual help, as an alternative to the existing conventional programs. The mean duration of stay differs from TZ to TZ (18-60 months). The staff consists mostly of former addicts, while the rest of the staff consists of medical professionals from the field of mental health, psychologists, defectologists, and pedagogues and similar. The aim of staying in TZ is a global change of lifestyle, including abstinence from the illegal substances, elimination of anti-social activities, gathering skills for job-finding and the development of pro-social efforts and values. In TZ, detoxification is the condition to enter the treatment and not the goal of it. Most of the patients who enter TZ already have histories of multiple drug abuse, significantly disturbed psychosocial functioning and consequently, significantly lower quality of life. …

Motivated by additional experimental hints of Lepton Flavour Universality violation in B decays, both in charged- and in neutral-current processes, we analyse the ingredients necessary to provide a combined description of these phenomena. By means of an Effective Field Theory (EFT) approach, based on the hypothesis of New Physics coupled predominantly to the third generation of left-handed quarks and leptons, we show how this is possible. We demonstrate, in particular, how to solve the problems posed by electroweak precision tests and direct searches with a rather natural choice of model parameters, within the context of a U(2)q ×U(2)ℓ flavour symmetry. We further exemplify the general EFT findings by means of simplified models with explicit mediators in the TeV range: coloured scalar or vector leptoquarks and colour-less vectors. Among these, the case of an SU(2)L-singlet vector leptoquark emerges as a particularly simple and successful framework.

This paper explores the potential methods for evaluating a healing system for asphalt pavements. The healing system under investigation involves compartmented calcium-alginate fibres encapsulating an asphalt binder healing agent (rejuvenator). This system presents a novel method of incorporating rejuvenators into asphalt pavement mixtures. The compartmented fibres are used to distribute the rejuvenator throughout the pavement mixture, thereby overcoming some of the problems associated with alternate asphalt pavement healing methods, i.e., spherical capsules and hollow fibres. The asphalt healing efficiency methods to be evaluated in this paper include: (i) standard test methods for asphalt pavements, such as the Indirect Tensile Strength test and the 4 Point Bending Fatigue test; and (ii) alternative fracture tests such as the Semi Circular Bend test. The study employs fracture theory in order to evaluate the efficiency of the damage repair. The research findings demonstrate that including compartmented calcium-alginate fibres encapsulating a rejuvenator into an asphalt pavement mix does not significantly improve the healing properties of the asphalt pavement. Nevertheless, the findings indicate that, with further enhancement, compartmented calcium alginate fibres may present a promising new approach for the development of self-healing asphalt pavement systems. Additionally, the test results indicate that the 4 point bend fatigue test is the most suitable test for evaluating the performance of self healing asphalt pavements.

An LCL filter utilized in an active front end (AFE) converter can generate significant resonance, which can affect quality and stability of the system. Thus, a proper active or passive damping technique and/or a suitable controller is required to be designed for the converter. The duty cycle constraint—though inevitable in practical inverter systems—is often ignored in most of the existing literature. The effects of measurement noise on filter control system performance must be considered and evaluated under different conditions. Finally, almost all inverter control systems are implemented digitally using microcontrollers. Consequently, the effects of sampling on control system stability and performance should be evaluated as well. Thus, this paper presents stability analysis of an AFE converter-based filter design with a complete practical system configuration, including saturation and sampling blocks and measurement noises. Mathematical analysis and simulations have been carried out to validate the proposed method.

We introduce two light scalar leptoquarks to accomodate the recent hints of lepton universality violation in $B$ meson decays. Scalar leptoquark $S_3 (\overline{3},3,1/3)$ with left-handed couplings to 2nd and 3rd generations of charged leptons and down-type quarks addresses both $R_{K^{(*)}}$ and $R_{D^{(*)}}$. The second state, $\tilde R_2(3,2,1/6)$, ensures compatibility with additional flavor constraints and secures unification of gauge couplings in the context of an $SU(5)$ GUT model without any conflict with the stringent limits from observed proton stability. We present the global fit of the flavor couplings and identify $B \to K \bar\nu\nu$ as the most sensitive channel to probe this model. Large couplings to $\tau$ leptons are confronted with the experimental searches for $\tau$ final states at the Large Hadron Collider. These searches comprise a study of decay products of the leptoquark pair production, as well as, and more importantly, an analysis of the high-mass $\tau\tau$ final states.

M1 and M2 activated macrophages (Mϕs) have different roles in inflammation. Because pathogens may first encounter resting cells, we investigated lipid mediator profiles prior to full activation. Human monocytes were differentiated with granulocyte Mϕ colony‐stimulating factor (GM‐CSF) or Mϕ colony‐stimulating factor (M‐CSF), which are known to prime toward M1 or M2 phenotypes, respectively. Lipid mediators released during resting conditions and produced in response to bacterial stimuli (LPS/N‐formylmethionyl‐leucyl‐phenylalanine or peptidoglycan) were quantified by liquid chromatography‐mass spectrometry. In resting conditions, both Mϕ phenotypes released primarily proresolving lipid mediators (prostaglandin E2 metabolite, lipoxin A4, and 18‐hydroxyeicosapentaenoic acid). A striking shift toward proinflammatory eicosanoids was observed when the same cells were exposed (30 min) to bacterial stimuli: M‐CSF Mϕs produced considerably more 5‐lipoxygenase products, particularly leukotriene C4, potentially linked to M2 functions in asthma. Prostaglandins were formed by both Mϕ types. In the M‐CSF cells, there was also an enhanced release of arachidonic acid and activation of cytosolic phospholipase A2. However, GM‐CSF cells expressed higher levels of 5‐lipoxygenase and 5‐lipoxygenase–activating protein, and in ionophore incubations these cells also produced the highest levels of 5‐hydroxyeicosatetraenoic acid. In summary, GM‐CSF and M‐CSF Mϕs displayed similar proresolving lipid mediator formation in resting conditions but shifted toward different proinflammatory eicosanoids upon bacterial stimuli. This demonstrates that preference for specific eicosanoid pathways is primed by CSFs before full M1/M2 activation.—Lukic, A., Larssen, P., Fauland, A., Samuelsson, B., Wheelock, C.E., Gabrielsson, S., Radmark, O. GM‐CSF– and M‐CSF–primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures. FASEB J. 31, 4370–4381 (2017). www.fasebj.org

Every long bone fracture in orthopedic surgery represents a possible scenario for devel- opment of embolism complication, especially the fat embolism. There is no scientific explanation why fat embolism occurs and what are the hypotheses for development of fat embolism or the proper way of prevention, but just speculations and possible theories in the evolution of the clinical picture of fat embolism syndrome. Throughout this chap- ter, the authors will explain the possible theories of development of fat embolism, risk factors, pathology, and pathophysiology during progress of the clinical picture and signs of the fat embolism syndrome and therapy.