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The mammalian cortex exerts top-down control of the thalamus by either enhancing or suppressing incoming sensory signals. This is thought to be accomplished via direct and indirect corticothalamic pathways that respectively increase and decrease the activity of thalamic relays1–4. Here, we discovered that in a reciprocally connected thalamocortical loop involving the dorsal midline thalamus, and unlike for sensory systems, top-down control by the cortex is predominantly indirect and through the thalamic reticular nucleus (TRN). Specifically, we found that the prelimbic area of the medial prefrontal cortex—a region mediating the selection and execution of emotional and motivated behavior5–8—shapes the decision to engage in and initiate instrumental avoidance responses via TRN projections to the paraventricular thalamus. Our findings reveal novel intra-thalamic circuit dynamics that gate cortical cognitive signals to shape goal-oriented actions.

Inspection and maintenance of the concrete Oil and Gas structures on the Norwegian Continental Shelf is a current focus area for owners and regulators. These ageing structures were installed between 1977 and 1995 and have been in operation in harsh environmental conditions throughout, and in some cases exceeding, their design service life. This paper results from work undertaken to describe repair methods and experience of repair works on the Norwegian Continental Shelf on ageing offshore structures. The part of this work related to inspection and maintenance of concrete structures forms the basis of this paper. Current experience shows that several concrete structures have a backlog of anomalies requiring assessment and possible remediation due to an acceleration of degradation over their lifetime. An increased frequency and range of defects means that stakeholders are expanding their capabilities to best manage these developing challenges. Maintenance of concrete structures demands an understanding of the degradation mechanisms, repair history, and original design requirements. A robust remediation management strategy should be followed to ensure a consistent and structured approach to all phases of the process, from inspection to documentation of remedial works. This paper aims to provide an overview of current experience and proposes a suitable remediation management strategy framework for offshore concrete structures.

Over the last half century, the existence of an additional thermal transition in between the glass transition and the Curie/melting transition has been frequently observed on vinylidenefluoride-based ferro-, pyro- and piezoelectric homo- and co-polymers. The transition has also been observed recently in some of the related relaxor-ferroelectric terpolymers. Despite its well-known existence and the rich history of its treatment in the literature, the origin(s) and a more or less complete picture of the mid-temperature transition have remained elusive until now. Over the years, several authors have put forth various explanations for the so-called mid-temperature transition — some complementary and some contradictory to each other. At the 17th IEEE International Symposium on Electrets (ISE-17) in Limerick, Ireland, in September 2019, the mysterious mid-temperature transition and its possible mechanism(s) became the subject of a panel discussion a) to mark the Golden Jubilee of the discovery of piezoelectricity in polyvinylidenefluoride (PVDF) by Heiji Kawai of Kobayashi Institute of Physical Research, Japan, as well as the Centennial of the first recognition of ferroelectricity in piezoelectric Seignette's or Rochelle salt. The panel put forward a new hypothesis that the mid-temperature transition is most likely a result of several interrelated processes that take place within the respective temperature range. The relevant processes include an upper glass transition or relaxation, a relaxation related to conformational disorder, possible imperfect/time-dependent structures formed as a result of thermal processing and secondary crystallization, as well as interface polarization effects at crystalline-amorphous boundaries. The article captures the essence of the panel discussion and the perspectives obtained therefrom to elucidate the complex mid-temperature transition in vinylidenefluoride-based ferro-, pyro- and piezoelectric homo-, co- and ter-polymers.

During sleep, neurons in the thalamic reticular nucleus (TRN) participate in distinct types of oscillatory activity. While the reciprocal synaptic circuits between TRN and sensory relay nuclei are known to underlie the generation of sleep spindles, the mechanisms regulating slow (in vitro conditions, TRN neurons can generate slow oscillations in a cell-intrinsic manner, with postsynaptic Group 1 metabotropic glutamate receptor (mGluR) activation leading to the generation of plateau potentials mediated by both T-type Ca2+ currents and Ca2+ -activated nonselective cation currents (ICAN). However, the identity of ICAN and the possible contribution of thalamic circuits to slow rhythmic activity remain unclear. Using thalamic slices derived from adult mice of either sex, we recorded slow forms of rhythmic activity in TRN neurons, which were mediated by fast glutamatergic thalamoreticular inputs but did not require postsynaptic mGluR activation. For a significant fraction of TRN neurons, synaptic inputs or brief depolarizing current steps led to long-lasting plateau potentials and persistent firing (PF), and in turn, resulted in sustained synaptic inhibition in postsynaptic relay neurons of the ventrobasal thalamus (VB). Pharmacological approaches indicated that plateau potentials were triggered by Ca2+ influx through T-type Ca2+ channels and mediated by Ca2+ and voltage-dependent transient receptor potential melastatin 4 (TRPM4) channels. Taken together, our results suggest that thalamic circuits can generate slow oscillatory activity, mediated by an interplay of TRN-VB synaptic circuits that generate rhythmicity and TRN cell-intrinsic mechanisms that control PF and oscillation frequency.Significance StatementSlow forms of thalamocortical rhythmic activity are thought to be essential for memory consolidation during sleep and the efficient removal of potentially toxic metabolites. In vivo, thalamic slow oscillations are regulated by strong bidirectional synaptic pathways linking neocortex and thalamus. Therefore, in vitro studies in the isolated thalamus can offer important insights about the ability of individual neurons and local circuits to generate different forms of rhythmic activity. We found that circuits formed by GABAergic neurons in the thalamic reticular nucleus (TRN) and glutamatergic relay neurons in the ventrobasal thalamus generated slow oscillatory activity, which was accompanied by persistent firing in TRN neurons. Our results identify both cell-intrinsic and synaptic mechanisms that mediate slow forms of rhythmic activity in thalamic circuits.

Survival depends on a balance between seeking rewards and avoiding potential threats, but the neural circuits that regulate this motivational conflict remain largely unknown. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited during conflict. Inactivation of aPVTCRF neurons during conflict biases animal’s response toward food, whereas activation of these cells recapitulates the food-seeking suppression observed during conflict. aPVTCRF neurons project densely to the nucleus accumbens (NAc), and activity in this pathway reduces food seeking and increases avoidance. In addition, we identified the ventromedial hypothalamus (VMH) as a critical input to aPVTCRF neurons, and demonstrated that VMH-aPVT neurons mediate defensive behaviors exclusively during conflict. Together, our findings describe a hypothalamic-thalamostriatal circuit that suppresses reward-seeking behavior under the competing demands of avoiding threats., Animals constantly balance seeking food with avoiding predators. Here, the authors report that CRF positive neurons in the paraventricular thalamus projecting to the nucleus accumbens in rats are an indispensable component of a feedback circuit that can interrupt appetitive behaviour in favor of a defensive response in the presence of a competing threat stimulus.

Epidemiology studies have found that a comorbidity exists between traumatic brain injury (TBI) and stress-related disorders. However, the anatomical and cellular bases for this association is poorly understood. An inability to extinguish the memory of a traumatic event lies at the core of many stress-related disorders. Experimental studies have shown that the medial pre-frontal cortex (mPFC), especially the infralimbic (IL) cortex, is required for extinction and for storing the memory of extinction. The output from the central nucleus of amygdala projects to the lateral hypothalamus, paraventricular nucleus, and central gray to regulate heart rate, stress hormone release, and freezing behavior, respectively. Projection neurons of the IL (layers II/III pyramidal neurons) are thought to stimulate GABAergic neurons in the amygdala, which, in turn, inhibit central amygdala output and reduce fear expression. Thus, loss and/or altered morphology of projection neurons of IL as a result of a mild TBI (mTBI) can compromise their ability to effectively inhibit the central amygdala, allowing the original fear memory to drive behavior. Using lateral mild fluid percussion injury (mFPI) in rats, we found that mFPI did not reduce neuronal numbers in the IL, but caused a significant reduction in overall dendritic spine density of both basal and apical dendrites on layer II/III pyramidal neurons. Spine numbers on layer V/VI pyramidal neurons were not significantly changed as a result of mFPI. The reduction in spine density on layer II/III pyramidal neurons we observed may diminish the efficacy of these neurons to inhibit the output of the central amygdala, thereby reducing the ability of the IL to suppress fear responses after extinction training. Consistent with this, mFPI rats display enhanced freezing behavior during and after extinction training as compared to sham-operated controls, although the ability to form contextual fear memories was not impaired. These results may have implications in stress-related disorders associated with mTBI.

A fundamental challenge for bioelectronics is to deliver power to miniature devices inside the body. Wires are common failure points and limit device placement. On the other hand, wireless power by electromagnetic or ultrasound waves must overcome absorption by the body and impedance mismatches between air, bone, and tissue. In contrast, magnetic fields suffer little absorption by the body or differences in impedance at interfaces between air, bone, and tissue. These advantages have led to magnetically-powered stimulators based on induction or magnetothermal effects. However, fundamental limitations in these power transfer technologies have prevented miniature magnetically-powered stimulators from applications in many therapies and disease models because they do not operate in clinical “high-frequency” ranges above 50 Hz. Here we show that magnetoelectric materials – applied in bioelectronic devices – enable miniature magnetically-powered neural stimulators that can operate up to clinically-relevant high-frequencies. As an example, we show that ME neural stimulators can effectively treat the symptoms of a hemi-Parkinson’s disease model in freely behaving rodents. We further demonstrate that ME-powered devices can be miniaturized to mm-sized devices, fully implanted, and wirelessly powered in freely behaving rodents. These results suggest that ME materials are an excellent candidate for wireless power delivery that will enable miniature bioelectronics for both clinical and research applications.

It is a cliche to label Vatican II a pastoral council. Like all cliches, this one tells us something about its subject but, as a cliche, it tends to trivialize that subject and even misdirect our attention. If we compare Vatican II with previous councils, especially with the Council of Trent, some interesting conclusions emerge. Those conclusions cause us to revisit the cliche, to deconstruct the conventional meaning attached to it, and to reconstruct it in a completely new way. From this exercise the pastoral character of Vatican II emerges vindicated but also radically transformed.

This article provides a general survey of developments over the past 100 years in the study of the history of the Catholic Church. It therefore provides the context for the other contributions in the issue, which deal with particular epochs or cultures. Included in it, for instance, are listings and analyses of major instruments of research such as encyclopedias, descriptions of shifts in historical method, assessments of the impact upon historians of events like the First and the Second Vatican Councils, and discussions of the vocation of Catholic historians of the Church.

A multidisciplinary panel of health professionals come together to share their experience in treating chronic gastrointestinal symptoms

Epigenetic mechanisms such as DNA methylation are essential regulators of the function and information storage capacity of neurons. DNA methylation is highly dynamic in the developing and adult brain, and is actively regulated by neuronal activity and behavioural experiences. However, it is presently unclear how methylation status at individual genes is targeted for modification. Here, we report that extra-coding RNAs (ecRNAs) interact with DNA methyltransferases and regulate neuronal DNA methylation. Expression of ecRNA species is associated with gene promoter hypomethylation, is altered by neuronal activity, and is overrepresented at genes involved in neuronal function. Knockdown of the Fos ecRNA locus results in gene hypermethylation and mRNA silencing, and hippocampal expression of Fos ecRNA is required for long-term fear memory formation in rats. These results suggest that ecRNAs are fundamental regulators of DNA methylation patterns in neuronal systems, and reveal a promising avenue for therapeutic targeting in neuropsychiatric disease states., DNA methylation in the brain is a dynamic process, but gene-specific regulation of this process is poorly understood. Here, Day and colleagues show that extra-coding RNAs interact with DNA methyltransferases and regulate neuronal DNA methylation to control gene expression in locus-specific manner in neurons.

Two-stage (pre-placed aggregate) concrete (TSC) consists of coarse aggregate, which is first deposited into the formwork, and grout, which is later pumped into the formwork from the bottom up to bind the stone together into a monolith. During the course of this study the formation of grout for two stage concrete was investigated using readily available 5 mm sand mixed in a slow speed paddle mixer. Silica fume and a superplasticizer were used in the mix to see if the necessary stability and fluidity could be achieved without the use of a specialized plant, essentially to see if TSC could be produced on a small scale using native Irish aggregates. A much higher degree of sedimentation was recorded during testing than was expected. As a result, the use of 5 mm sand and a slow speed mixer in combination were found to be not conducive to the successful production of TSC grout, without further research and testing.

Cost containment in prescribing budgets is, and always will be, a key priority in any health service with limited resources. Therefore, a number of primary care trusts (PCT) have recently initiated pharmacy-led switches of 5-aminosalicylic acids (5-ASAs), with the intention of reducing prescribing budgets. However, this has generated considerable controversy among gastroenterologists, as there is concern that the clinical consequences of such programmes have not been adequately explored. PCTs are currently under no obligation to consult secondary care prior to initiating pharmacy-led switches. In a secondary care-led condition such as inflammatory bowel disease (IBD), this seems highly counterintuitive. If gastroenterologists were to be consulted, how would we respond, and what could we contribute? This article examines the clinical consequences of PCT-initiated switch programmes in IBD, and the knock-on effects on patients and the secondary care gastroenterology community. For a switch programme to be justified, the financial benefits it imparts must be balanced against its clinical effects. Here, we consider what the clinical effects of a 5-ASA switch might be. Many gastroenterologists express concern over such programmes, but is there evidence for a detrimental effect, and what is the experience that exists among the secondary care community to inform our approach? Many gastroenterology specialists have already encountered pharmacy-led switches firsthand, and some of their experiences provide immediate cause for concern. Although anecdotal, reports abound that 5-ASA switches have been followed by flares of active disease and other adverse effects in a worrying number of patients. For example, in one recent pharmacy-led switch programme, a patient showed a significant drop in his white blood cell count after his 5-ASA was changed, and another two patients experienced bouts of diarrhoea. In a particularly worrying case, a young woman who was very concerned about her 5-ASA being switched was subsequently admitted with an episode …

L'article reproduit les reponses a des questions donnees par quatre temoins et acteurs contemporains importants de l'historiographie de la Compagnie de Jesus durant les temps modernes. Les questions portent surtout sur les traits saillants des apports nouveaux sur l'histoire des jesuites, sur sa specificite, sur la redecouverte du caractere europeen de la Compagnie et les nouveaux problemes historiques poses.

Although responsibility for out-of-hours (OOH) general practice care (provided between 6.30 pm and 8 am and on weekends and public holidays) changed substantially in 2004, the same GPs who had previously provided this care often continued as the clinical mainstays of the service. Before 2004, patients were often seen OOH by their own GP, or at least a GP they knew from their practice, but this continuity has now been lost and has led to a lack of confidence and trust in OOH services, reflected in a greater propensity for patients to complain and to concerns about patient safety.1,2 Primary care now needs to rise to the challenge of re-engaging with OOH care in the context of rising patient demands and expectations, and the imperatives of patient safety and clinical governance. Most GPs working in OOH services cover much larger geographical areas than previously when cover was limited to the practice area or a GP cooperative of several practices. The involvement of local GPs who know the area and the local health services remains important, not least for patient safety. Lack of such knowledge appears to have contributed to OOH errors in the past.3 The model of OOH services run by less experienced GPs, with the best trained and most experienced concentrating their efforts …

This paper reports the findings of a study of attitudes towards data security issues and awareness of the potential risks of social networking sites, most notably the possibility of identity fraud. The population for this study is people in the 18-24 age group living in Ireland, for which the students of one of the country's main universities were used as a proxy sample. The main finding is that many people have a very casual attitude towards data backup and password protection, a considerable number are not adequately aware of the threats posed by viruses transmitted via portable devices and other such means, and a lot of young people are openly publishing personal information of a sensitive nature that could potentially be maliciously exploited. peer-reviewed

La citta e i poveri: Milano e le terre lombarde dal Rinascimento all'eta spagnola. Edited by Danilo Zardin. [Edizioni Universitarie Jaca, Vol. 100.] (Milan:Jaca Book. 1995. Pp. 431.) This volume contains, besides the introduction by the editor, fifteen papers first presented at a conference in Milan in 1992. It is a particularly felicitous achievement for at least three reasons. First, it has the advantage of focusing on a specific locality, a locality extraordinarily rich in historical sources, and of approaching it from a variety of perspectives. This assures depth in coverage and also helps forestall facile generalizations from just one kind of evidence. Second, it is a good example of integration of the study of religion, literature, economics, and politics. Third, although the contributors are with the exception of Brian Pullan not well known outside Italy, they are all skilled practitioners of our metier, beginning with the editor, Danilo Zardin, who provides a fine overview of the volume in his introduction. The importance of the subject can hardly be overestimated, for it is still with us in our cities today. Sad to say, there is little indication that we handle it better than did early modern Italians. Even given the greater complexity of the urban situation today, there is some indication that we handle it worse. In any case, the subject has also been of keen interest historiographically ever since Pullan's groundbreaking Rich and Poor in Venice (1971), in which he challenged the sharp contrast historians drew between Protestant and Catholic poor relief. As the dean of such studies, Pullan's contribution on "poverty," "charity," and "new forms of social assistance" from the fifteenth to the seventeenth century is, therefore, of special interest and weight. He cautions against drawing too firm a line of demarcation between late medieval and early modern attitudes and practices in these regards and also against doing the same between Protestants and Catholics. Nonetheless, differences there were, and in the latter case he points specifically to the continuation of confraternities within Catholic territories, once again vindicating recent scholarship on the utterly crucial but long-forgotten role these institutions played in almost every aspect of Catholic culture. Confraternities appear passim in any number of articles, for, besides being an institution in their own right, they funded or otherwise supported other institutions or themselves developed into different ones. For that reason Angelo Bianchi's article on the Somascans is especially illuminating. From what amounted originally to a confraternity gathered around Gerolamo Miani that created the first orphanages, as distinct from foundling homes, it devolved into a religious order. …

The mission of Radiographic Integrated Test Stand-6 (RITS-6) facility is to provide the underlying science and technology for pulsed-power-driven flash radiographic X-ray sources for the National Nuclear Security Administration (NNSA). Flash X-ray radiography is a penetrating diagnostic to discern the internal structure in dynamic experiments. Short (~50 nanosecond (ns) duration) bursts of very high intensity Xrays from mm-scale source sizes are required at a variety of voltages to address this mission. RITS-6 was designed and is used to both develop the accelerator technology needed for these experiments and serves as the principal test stand to develop the high intensity electron beam diodes that generate the required X-ray sources. RITS is currently in operation with three induction cavities (RITS-3) with a maximum voltage output of 5.5 MV and is classified as a low hazard non-nuclear facility in accordance with CPR 400.1.1, Chapter 13, Hazards Identification/Analysis and Risk Management. The facility will be expanded from three to six cavities (RITS-6) effectively doubling the operating voltage. The increase in the operating voltage to above 10 MV has resulted in RITS-6 being classified as an accelerator facility. RITS-6 will come under DOE Order 420.2B, Safety of Accelerator Facilities. The hazards of RITS are detailedmore » in the "Safety Assessment Document for the Radiographic Integrated Test Stand Facility." The principal non-industrial hazard is prompt x-ray radiation. As the operating voltage is increased, both the penetration power and the total amount (dose) of x-rays are increased, thereby increasing the risk to local personnel. Fixed site shielding (predominantly concrete walls and a steel/lead skyshine shield) is used to attenuate these x-rays and mitigate this risk. This SAND Report details the anticipated x-ray doses, the shielding design, and the anticipated x-ray doses external to this shielding structure both in areas where administrative access control restricts occupation and in adjacent uncontrolled areas.« less

Finzone e santita tra medioevo ed eta moderna. Edited by Gabriella Zarri. (Turin: Rosenberg Sellier. 1991. Pp. 570. Lire 69,000 paperback. This volume contains twenty-two studies of a crucially important but neglected subject, the transformation on the official level of the definition of sanctity that happened in the early modern era. The book grew out of a meeting of scholars convoked to discuss the problem and a subsequent meeting at which the results of their research were compared. This process established the coherence of the volume, whose themes the editor presents concisely in her opening essay, while warning against reading the volume as if it were a "kaleidoscope" without firm structure (p. 9). The authors chart the evolution of the definition by paying attention principally to its verso side, that is, by examining the change in definition of sanctity's opposite number as it moved from "false" to "simulated" sanctity. Among the contributors are some well known on this side of the Atlantic, almost guaranteeing beforehand the high quality of the product -- Zarri herself, for instance, and Andre Vauchez, Adriano Prosperi, Gianvittorio Signorotto, Anne Jacobson Schutte, and Mario Rosa. While the book has as its central theme the change of the idea of sanctity or phony sanctity, it for the most part arrives at conclusion through the analysis of special cases, often with explicit correlation to the great shifts in culture and religious sensibilities of those centuries. The shift in understanding of what constituted sanctity was emblematic of the larger shifts. This makes the book an important contribution to the social history of that long era. With one exception, all the articles that deal with cases deal with women. Thus the volume makes a similarly important contribution to women's studies and to the history of male-female conflict. The juridical expression of the shift, nonetheless, provides a touchstone throughout for testing its course, especially in the important norms laid down by Urban VIII in the early seventeenth century and by Benedict XIV in the mid-eighteenth The volume terminates at that date with Rosa's excellent analysis Pope Lambertini but, significantly, the last name he mentions, the last to appear in the whole book is Bernadette Soubirous. Zarri briefly describes the essence of the shift in her introductory essay (p. 18); others give it substance in detailed studies and indicate its complexity, and Prosperi generalizes about it most effectively, relating it even to changes in ecclesiastical historiography. What was the shift? In the earlier phase the concern with the issue was more "theological" that is, intent on distinguishing "true" sanctity, inspired by God or the Holy Spirit, from "false" sanctity, inspired by the Devil. Within this framework visions and prophecies, for instance, were taken as marks of holiness -- or as marks of diabolical Intervention, with witchcraft one of its important manifestations. …

Gone are the days when most patients tolerated impersonal service from their physicians and health-care providers in general. Every day, customer and patient satisfaction becomes more critical to a health-care provider's success and survival. Open communications, Internet-informed patients, and aggressive watch groups reveal those health-care providers who consistently deliver poor service. Most health-care providers employ patient satisfaction surveys to monitor their level of service; however, written and telephone surveys seldom provide the surveyor the insight necessary to provide differentiating service because of a large illiteracy rate and fear of reprisal. Toward this end, a well-trained mystery patients offers the health-care provider greater insight into how service is dispensed to its customers and patients. This article offers an aggregate of mystery patient insights into delivering clinical laboratory services both in hospital and medical practice environments, supported with insightful information into creating winning service strategies.