ORGANISATION, COOPERATION AND REDUCTION: A SOCIO-ECONOMIC ANALYSIS OF ILLEGAL MARKET ACTORS FACILITATING IRREGULAR MIGRATION AT EU-INTERNAL TRANSIT POINTS

The facilitation of irregular migration by organised criminal groups [OCGs] at EU-internal transit points represents a specific illegal market type. This PhD thesis uses a mixed methodology approach to study this market with a focus on Italy, one of the main entry and transit countries for irregular migrants aiming to reach Central and Northern Europe, as well as the pulsating heart of intense EU-public and political debate around issues of mismanaged, undocumented immigration. While the debate has concentrated on the organised smuggling of irregular migrants via sea routes, less attention has been paid to EU-inland routes. What is known about the latter is mainly restricted to sporadic cases in which smuggling journeys have ended tragically. This has led to the rather uninformed and sensationalist notion that the market for human smuggling is monopolised by highly structured and sophisticated transnational OCGs. However, existing empirical evidence rather suggests OCGs to be weakly-tied and fragmented in structure. Considering that these OCGs operate on a highly uncertain market, which lacks in institutional control and formal contracts, it becomes not only interesting, but vital to understand how these OCGs nevertheless execute their business successfully. The purpose of this thesis is to shed light on the organisational structure of OCGs operating on this illegal market type, to elucidate how its decentralised structure influences the market\u2019s operation, and to analyse relational mechanisms that induce cooperative rather than opportunistic behaviour by illegal market actors. In doing so, the specificities and parallels of this distinct illegal market actor are compared to human smuggling organisations operating at EU-external borders. On the basis of these results, novel market reduction measures are pointed out, which are context-tailored, as well as more generally applicable to countering human smuggling into and within the EU. The study aims to achieve its purpose through a context-specific socio-economic analysis of organised human smuggling at transit points internally to the EU by means of: (i) a critical review of the literature on EU-related human smuggling; (ii) a thematic analysis of secondary sources as well as expert interviews on EU-internal organised human smuggling, and finally, (iii) a social network analysis of a selected, large-scale human smuggling organisation in Northern Italy. Together, these three different analyses lead to significant conclusions. OCGs involved in EU-internal human smuggling exhibit a decentralised organsational structure, which includes at most a two-tier level, including resourceful smugglers at the top and precarious individuals at the bottom. These OCGs are constituted not only by foreign- but also largely by European actors. Common ethnicity appears to facilitate cooperation between smugglers, as well as the criminal experience of a few. Compared to increasingly structured OCGs operating at the borders of Europe, the EU-internal human smuggling market appears still less organised and less violent and/or life-threatening for migrants. The latter is exhibited by a shift from physical transport to the progressive use of fraudulent documents on the EU-internal human smuggling market, which however might indicate increased involvement of resourcesful smugglers. It is argued that such a highly resilient illegal market structure can only be countered through (i) the improved targeting of high-tier smugglers but more importantly, necessitates (ii) recruitment prevention strategies that target the marginalisation and socio-economic precarity of smugglers, which are measures that notably overlap with the aim to reduce the demand of irregular migrants for smuggling services in the first place

Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle

The human hair follicle (HF) exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1) prolonging active hair growth (anagen) and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4) also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM) treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2) were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease

What have We Learned from “Perturbing” the Human Cortical Motor System with Transcranial Magnetic Stimulation?

The purpose of this paper is twofold. First, we will review different approaches that one can use with transcranial magnetic stimulation (TMS) to study both its effects on motor behavior and on neural connections in the human brain. Second, we will present evidence obtained in TMS-based studies showing that the dorsal premotor area (PMd), the ventral premotor area (PMv), the supplementary motor area (SMA), and the pre-supplementary motor area (pre-SMA) each have different roles to play in motor behavior. We highlight the importance of the PMd in response selection based on arbitrary cues and in the control of arm movements, the PMv in grasping and in the discrimination of bodily actions, the SMA in movement sequencing and in bimanual coordination, and the pre-SMA in cognitive control. We will also discuss ways in which TMS can be used to chart “true” cerebral reorganization in clinical populations and how TMS might be used as a therapeutic tool to facilitate motor recovery after stroke. We will end our review by discussing some of the methodological challenges and future directions for using this tool in basic and clinical neuroscience

Testosterone Trajectories and Reference Ranges in a Large Longitudinal Sample of Male Adolescents

Pubertal dynamics plays an important role in physical and psychological development of children and adolescents. We aim to provide reference ranges of plasma testosterone in a large longitudinal sample. Furthermore, we describe a measure of testosterone trajectories during adolescence that can be used in future investigations of development.We carried out longitudinal measurements of plasma testosterone in 2,216 samples obtained from 513 males (9 to 17 years of age) from the Avon Longitudinal Study of Parents and Children. We used integration of a model fitted to each participant's testosterone trajectory to calculate a measure of average exposure to testosterone over adolescence. We pooled these data with corresponding values reported in the literature to provide a reference range of testosterone levels in males between the ages of 6 and 19 years.The average values of total testosterone in the ALSPAC sample range from 0.82 nmol/L (Standard Deviation [SD]: 0.09) at 9 years of age to 16.5 (SD: 2.65) nmol/L at 17 years of age; these values are congruent with other reports in the literature. The average exposure to testosterone is associated with different features of testosterone trajectories such as Peak Testosterone Change, Age at Peak Testosterone Change, and Testosterone at 17 years of age as well as the timing of the growth spurt during puberty.The average exposure to testosterone is a useful measure for future investigations using testosterone trajectories to examine pubertal dynamics

A practical guide for the study of human and murine sebaceous glands in situ

The skin of most mammals is characterised by the presence of sebaceous glands (SGs), whose predominant constituent cell population is sebocytes, that is, lipid-producing epithelial cells, which develop from the hair follicle. Besides holocrine sebum production (which contributes 90% of skin surface lipids), multiple additional SG functions have emerged. These range from antimicrobial peptide production and immunomodulation, via lipid and hormone synthesis/metabolism, to the provision of an epithelial progenitor cell reservoir. Therefore, in addition to its involvement in common skin diseases (e.g. acne vulgaris), the unfolding diversity of SG functions, both in skin health and disease, has raised interest in this integral component of the pilosebaceous unit. This practical guide provides an introduction to SG biology and to relevant SG histochemical and immunohistochemical techniques, with emphasis placed on in situ evaluation methods that can be easily employed. We propose a range of simple, established markers, which are particularly instructive when addressing specific SG research questions in the two most commonly investigated species in SG research, humans and mice. To facilitate the development of reproducible analysis techniques for the in situ evaluation of SGs, this methods review concludes by suggesting quantitative (immuno-)histomorphometric methods for standardised SG evaluation

Responding to Climate Change: The Economy and Economics - Part of the Problem and Solution

The Climate Change Starter’s Guide provides an introduction and overview for education planners and practitioners on the wide range of issues relating to climate change and climate change education, including causes, impacts, mitigation and adaptation strategies, as well as some broad political and economic principles. The aim of this guide is to serve as a starting point for mainstreaming climate change education into school curricula. It has been created to enable education planners and practitioners to understand the issues at hand, to review and analyse their relevance to particular national and local contexts, and to facilitate the development of education policies, curricula, programmes and lesson plans. The guide covers four major thematic areas: 1. the science of climate change, which explains the causes and observed changes; 2. the social and human aspects of climate change including gender, health, migration, poverty and ethics; 3. policy responses to climate change including measures for mitigation and adaptation; and 4. education approaches including education for sustainable development, disaster reduction and sustainable lifestyles. A selection of key resources in the form of publication titles or websites for further reading is provided after each of the thematic sections

Neural Mechanisms of Hair Growth Control

Clinical and experimental observations have long suggested that skin nerves have “trophic” functions in hair follicle development, growth and/or cycling, even though the molecular and cellular basis of the underlying neuroepithelial interactions has remained obscure. Here, we critically review currently available evidence arguing in favor of or against the existence of neural mechanisms of hair growth control, and outline why the murine hair cycle provides an excellent experimental system for characterizing and manipulating piloneural interactions. Summarizing relevant, recent data from the C57BL/6 mouse model, it is pointed out that the sensory and autonomic innervation of normal pelage hair follicles, the substance P skin content, and cutaneous mast cell-nerve contacts show striking changes during synchronized hair follicle cycling. Furthermore, the murine hair follicle appears to be both a source and a target of neurotrophins, whereas neuropharmacologic manipulations alter murine hair follicle cycling in vivo. For example, anagen is induced by substance P or adrenocorticotropin (ACTH), and by the experimentally triggered release of neuropeptides from sensory nerves and of neurotransmitters from adrenergic nerves. Taken together, this argues in favor of neuroepithelial interactions as regulatory elements in hair growth control and suggests that the study of piloneural interactions promises important insights into general principles of neuroepithelial communication, namely during epithelial morphogenesis and remodeling. We delineate a hypothetical working model of piloneural interactions and propose that targeted manipulations deserve systematic exploration as a novel strategy for managing hair growth disorders. Journal of Investigative Dermatology Symposium Proceedings 2:61–68, 199

Hair-Cycle-Associated Remodeling of the Peptidergic Innervation of Murine Skin, and Hair Growth Modulation by Neuropeptides

As the neuropeptide substance P can manipulate murine hair growth in vivo, we here further studied the role of sensory neuropeptides in hair follicle biology by determining the distribution and hair-cycle-dependent remodeling of the sensory innervation in C57BL/6 mouse back skin. Calcitonin-gene-related peptide, substance P, and peptide histidine methionine (employed as vasoactive intestinal peptide marker) were identified by immunohistochemistry. All of these markers immunolocalized to bundles of nerve fibers and to single nerve fibers, with distinct distribution patterns and major hair-cycle-associated changes. In the epidermis and around the distal hair follicle and the arrector pili muscle, only calcitonin-gene-related peptide immunoreactive nerve fibers were visualized, whereas substance P and peptide histidine methionine immunoreactive nerve fibers were largely restricted to the dermis and subcutis. Compared to telogen skin, the number of calcitonin-gene-related peptide, substance P, and peptide histidine methionine immunoreactive single nerve fibers increased significantly (p < 0.01) during anagen, including around the bulge region (the seat of epithelial stem cells). Substance P significantly accelerated anagen progression in murine skin organ culture, whereas calcitonin-gene-related peptide and a substance-P-inhibitory peptide inhibited anagen (p < 0.05). The inhibitory effect of calcitonin-gene-related peptide could be antagonized by coadministrating substance P. In contrast to substance P, calcitonin-gene-related peptide failed to induce anagen when released from subcutaneous implants. This might reflect a differential functional assignment of the neuropeptides calcitonin-gene-related peptide and substance P in hair growth control, and invites the use of neuropeptide receptor agonists and antagonists as novel pharmacologic tools for therapeutic hair growth manipulation