Morphofunctional adaptations of the olfactory mucosa in postnatally developing rabbits

Rabbits are born blind and deaf and receive unusually limited maternal care. Consequently, their suckling young heavily rely on the olfactory cue for nipple attachment. However, the postnatal morphofunctional adaptations of olfactory mucosa (OM) are not fully elucidated. To clarify on the extent and the pattern of refinement of the OM following birth in the rabbit, morphologic and morphometric analysis of the mucosa were done at neonatal (0-1 days), suckling (2 weeks), weanling (4 weeks), and adult (6-8 months) stages of postnatal development. In all the age groups, the basic components of the OM were present. However, proliferative activity of cells of the mucosal epithelium decreased with increasing age as revealed by Ki-67 immunostaining. Diameters of axon bundles, packing densities of olfactory cells, and cilia numbers per olfactory cell knob increased progressively with age being 5.5, 2.1, and 2.6 times, respectively, in the adult as compared with the neonate. Volume fraction values for the bundles increased by 5.3% from birth to suckling age and by 7.4% from weaning to adulthood and the bundle cores were infiltrated with blood capillaries in all ages except in the adult where such vessels were lacking. The pattern of cilia projection from olfactory cell knobs also showed age-related variations, that is, arose as a tuft from the tips of the knobs in neonates and sucklings and in a radial pattern from the knob bases in weanlings and adults. These morphological changes may be attributed to the high olfactory functional demand associated with postnatal development in the rabbit.

'A rose is a rose is a rose', but at-risk criteria differ

Background: Over the last 15 years, efforts to detect psychoses early in their prodromal states have greatly progressed; meanwhile, ultra-high risk (UHR) criteria have been the subject of such consensus that parts of them have been proposed for inclusion in DSM-5 in terms of an attenuated psychosis syndrome. However, it is frequently unacknowledged that the definitions and operationalizations of UHR-related at-risk criteria, including the relevant attenuated psychotic symptoms, vary considerably across centers and time and, thus, between prediction studies. Methods: These variations in UHR criteria are described and discussed with reference to the rates of transition to psychosis, their prevalence in the general population and the proposed new operationalization of the attenuated psychosis syndrome. Results: A comparison of samples recruited according to different UHR operationalizations reveals differences in the distribution of UHR criteria and transition rates as well as in the prevalence rates of at-risk criteria in the general population. Conclusion: The evidence base for the introduction of such a new syndrome is weaker than the number of studies using supposedly equal UHR criteria would at first suggest. Thus, studies comparing the effects of different (sub-)criteria not only on transition rates and outcomes but also on other important aspects, such as neurocognitive performance and brain imaging results, are necessary. Meanwhile, the preliminary attenuated psychosis syndrome in DSM-5 should not follow an altogether new definition but, rather, the currently most reliable UHR definition, which must still demonstrate its reliability and validity outside specialized psychiatric services.

Prediction of psychosis in clinical high-risk patients by the Schizotypal Personality Questionnaire. Results of the EPOS project

OBJECTIVE: Schizotypal features indicate proneness to psychosis in the general population. It is also possible that they increase transition to psychosis (TTP) among clinical high-risk patients (CHR). Our aim was to investigate whether schizotypal features predict TTP in CHR patients. METHODS: In the EPOS (European Prediction of Psychosis Study) project, 245 young help-seeking CHR patients were prospectively followed for 18 months and their TTP was identified. At baseline, subjects were assessed with the Schizotypal Personality Questionnaire (SPQ). Associations between SPQ items and its subscales with the TTP were analysed in Cox regression analysis. RESULTS: The SPQ subscales and items describing ideas of reference and lack of close interpersonal relationships were found to correlate significantly with TTP. The co-occurrence of these features doubled the risk of TTP. CONCLUSIONS: Presence of ideas of reference and lack of close interpersonal relations increase the risk of full-blown psychosis among CHR patients. This co-occurrence makes the risk of psychosis very high.

Psychosocial outcome in patients at clinical high risk of psychosis: a prospective follow-up

Purpose In patients at clinical high risk (CHR) of psychosis, transition to psychosis has been the focus of recent studies. Their broader outcome has received less attention. We studied psychosocial state and outcome in CHR patients. Methods In the European Prediction of Psychosis Study, 244 young help-seeking CHR patients were assessed with the Strauss and Carpenter Prognostic Scale (SCPS) at baseline, and 149 (61.1 %) of them were assessed for the second time at the 18-month follow-up. The followed patients were classified into poor and good outcome groups. Results Female gender, ever-married/cohabitating relationship, and good working/studying situation were associated with good baseline SCPS scores. During follow-up, patients’ SCPS scores improved significantly. Good follow-up SCPS scores were predicted by higher level of education, good working/studying status at baseline, and white ethnicity. One-third of the followed CHR patients had poor global outcome. Poor working/studying situation and lower level of education were associated with poor global outcome. Transition to psychosis was associated with baseline, but not with follow-up SCPS scores or with global outcome. Conclusion The majority of CHR patients experience good short-term recovery, but one-third have poor psychosocial outcome. Good working situation is the major indicator of good outcome, while low level of education and non-white ethnicity seem to be associated with poor outcome. Transition to psychosis has little effect on psychosocial outcome in CHR patients. In treating CHR patients, clinicians should focus their attention on a broader outcome, and not only on preventing transition to psychosis.

The Strauss and Carpenter Prognostic Scale in subjects clinically at high risk of psychosis

Objective:  To investigate the predictive value of the Strauss and Carpenter Prognostic Scale (SCPS) for transition to a first psychotic episode in subjects clinically at high risk (CHR) of psychosis. Method:  Two hundred and forty-four CHR subjects participating in the European Prediction of Psychosis Study were assessed with the SCPS, an instrument that has been shown to predict outcome in patients with schizophrenia reliably. Results:  At 18-month follow-up, 37 participants had made the transition to psychosis. The SCPS total score was predictive of a first psychotic episode (P < 0.0001). SCPS items that remained as independent predictors in the Cox proportional hazard model were as follows: most usual quality of useful work in the past year (P = 0.006), quality of social relations (P = 0.006), presence of thought disorder, delusions or hallucinations in the past year (P = 0.001) and reported severity of subjective distress in past month (P = 0.003). Conclusion:  The SCPS could make a valuable contribution to a more accurate prediction of psychosis in CHR subjects as a second-step tool. SCPS items assessing quality of useful work and social relations, positive symptoms and subjective distress have predictive value for transition. Further research should focus on investigating whether targeted early interventions directed at the predictive domains may improve outcomes.

Not in the Legends

In writing “Not in the Legends”, one of the images and concepts which constantly returned was that of pilgrimage. I began to write these poems while studying abroad in London, after having passed the previous semester in France and travelling around Europe. There was something in the repetition of sightseeing— walking six miles in Luxembourg to see the grave of General Patton, taking photographs of the apartment where Sylvia Plath ended her life, bowing before the bones of saints, searching through Père Lachaise for the grave of Théodore Gericault— which struck me as numinous and morbid. At the same time, I came to love living abroad and I grew discontent with both remaining and returning. I wanted the opportunity to live everywhere all the time and not have to choose between home and away. Returning from abroad, I turned my attention to the landscape of my native country. I found in the New England pilgrims a narrative of people who had left their home in search of growth and freedom. In these journeys I began to appreciate the significance of place and tried to understand what it meant to move from one place to another, how one chose a home, and why people searched for meaning in specific locations. The processes of moving from student to worker and from childhood to adulthood have weighed on me. I began to see these transitions towards maturity as travels to a different land. Memory and nostalgia are their own types of pilgrimage in their attempts to return to lost places, as is the reading of literature. These pilgrimages, real and metaphorical, form the thematic core of the collection. I read the work of many poets who came before me, returning to the places where the Canon was forged. Those poets have a large presence in the work I produced. I wondered how I, as a young poet, could earn my own place in the tradition and sought models in much the same way a painter studies the brushstrokes of a master. In the process, I have tried to uncover what it means to be a poet. Is it something like being a saint? Is it something like being a colonist? Or is to be the one who goes in search of saints and colonists? In trying to measure my own life and work based on the precedent, I have questioned what role era and generation have on the formation of identity. I focused my reading heavily on the early years of English poetry, trying to find the essence of the time when the language first achieved the transcendence of verse. In following the development of English poetry through Coleridge, John Berryman, and Allison Titus, I have explored the progression of those basic virtues in changing contexts. Those bearings, applied to my modern context, helped to shape the poetry I produced. Many of the poems in “Not in the Legends” are based on my own personal experience. In my recollections I have tried to interrogate nostalgia rather than falling into mere reminiscence. Rather than allowing myself poems of love and longing, I have tried to find the meaning of those emotions. A dominant conflict exists between adventure and comfort which mirrors the central engagement with the nature of being “here” or “there”. It is found in scenes of domesticity and wilderness as I attempt to understand my own simultaneous desire for both. For example, in “Canned Mangoes…” the intrusion of nature, even in a context as innocuous as a poem by Sir Walter Raleigh, unravels ordinary comforts of the domestic sphere. The character of “The Boy” from Samuel Beckett’s Waiting for Godot proved such an interesting subject for me because he is one who can transcend the normal boundaries of time and place. The title suggests connections to both place and time. “Legends” features the dual meaning of both myths and the keys to maps. To propose something “Not in the Legends” is to find something which has no precedent in our histories and our geographies, something beyond our field of knowledge and wholly new. One possible interpretation I devised was that each new generation lives a novel existence, the future being the true locus of that which is beyond our understanding. The title comes from Keats’ “Hyperion, a Fragment”, and details the aftermath of the Titanomachy. The Titans, having fallen to the Olympians, are a representation of the passing of one generation for the next. Their dejection is expressed by Saturn, who laments: Not in my own sad breast, Which is its own great judge and searcher out, Can I find reason why ye should be thus: Not in the legends of the first of days… (129-132) The emotions of the conquered Titans are unique and without antecedent. They are experiencing feelings which surpass all others in history. In this, they are the equivalent of the poet who feels that his or her own sufferings are special. In contrast are Whitman’s lines from “Song of Myself” which serve as an epigraph to this collection. He contends for a sense of continuity across time, a realization that youth, age, pleasure, and suffering have always existed and will always exist. Whitman finds consolation in this unity, accepting that kinship with past generations is more important that his own individuality. These opposing views offer two methods of presenting the self in history. The instinct of poetry suggests election. The poet writes because he feels his experiences are special, or because he believes he can serve as a synecdoche for everyone. I have fought this instinct by trying to contextualize myself in history. These poems serve as an attempt at prosopography with my own narrative a piece of the whole. Because the earth abides forever, our new stories get printed over the locations of the old and every place becomes a palimpsest of lives and acts. In this collection I have tried to untangle some of those layers, especially my own, to better understand the sprawling legend of history.

Nanoparticle-based test measures overall propensity for calcification in serum

Vascular and soft tissue calcification contributes to cardiovascular morbidity and mortality in both the general population and CKD. Because calcium and phosphate serum concentrations are near supersaturation, the balance of inhibitors and promoters critically influences the development of calcification. An assay that measures the overall propensity for calcification to occur in serum may have clinical use. Here, we describe a nanoparticle-based assay that detects, in the presence of artificially elevated calcium and phosphate concentrations, the spontaneous transformation of spherical colloidal primary calciprotein particles (CPPs) to elongate crystalline secondary CPPs. We used characteristics of this transition to describe the intrinsic capacity of serum to inhibit the precipitation of calcium and phosphate. Using this assay, we found that both the sera of mice deficient in fetuin-A, a serum protein that inhibits calcification, and the sera of patients on hemodialysis have reduced intrinsic properties to inhibit calcification. In summary, we developed a nanoparticle-based test that measures the overall propensity for calcification in serum. The clinical use of the test requires evaluation in a prospective study.

Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study

Objectives: Neurofunctional alterations are correlates of vulnerability to psychosis, as well as of the disorder itself. How these abnormalities relate to different probabilities for later transition to psychosis is unclear. We investigated vulnerability- versus disease-related versus resilience biomarkers of psychosis during working memory (WM) processing in individuals with an at-risk mental state (ARMS). Experimental design: Patients with “first-episode psychosis” (FEP, n = 21), short-term ARMS (ARMS-ST, n = 17), long-term ARMS (ARMS-LT, n = 16), and healthy controls (HC, n = 20) were investigated with an n-back WM task. We examined functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (sMRI) data in conjunction using biological parametric mapping (BPM) toolbox. Principal observations: There were no differences in accuracy, but the FEP and the ARMS-ST group had longer reaction times compared with the HC and the ARMS-LT group. With the 2-back > 0-back contrast, we found reduced functional activation in ARMS-ST and FEP compared with the HC group in parietal and middle frontal regions. Relative to ARMS-LT individuals, FEP patients showed decreased activation in the bilateral inferior frontal gyrus and insula, and in the left prefrontal cortex. Compared with the ARMS-LT, the ARMS-ST subjects showed reduced activation in the right inferior frontal gyrus and insula. Reduced insular and prefrontal activation was associated with gray matter volume reduction in the same area in the ARMS-LT group. Conclusions: These findings suggest that vulnerability to psychosis was associated with neurofunctional alterations in fronto-temporo-parietal networks in a WM task. Neurofunctional differences within the ARMS were related to different duration of the prodromal state and resilience factors

Securities: Its Conception and Protection of Interests of its Holders

Theoretical studies of the problems of the securities markets in the Russian Federation incline to one or other of the two traditional approaches. The first consists of comparing the definition of "valuable paper" set forth in the current legislation of the Russian Federation, with the theoretical model of "Wertpapiere" elaborated by German scholars more than 90 years ago. The problem with this approach is, in Mr. Pentsov's opinion, that any new features of the definition of "security" that do not coincide with the theoretical model of "Wertpapiere" (such as valuable papers existing in non-material, electronic form) are claimed to be incorrect and removed from the current legislation of the Russian Federation. The second approach works on the basis of the differentiation between the Common Law concept of "security" and the Civil Law concept of "valuable paper". Mr. Pentsov's research, presented in an article written in English, uses both methodological tools and involves, firstly, a historical study of the origin and development of certain legal phenomena (securities) as they evolved in different countries, and secondly, a comparative, synchronic study of equivalent legal phenomena as they exist in different countries today. Employing the first method, Mr. Pentsov divided the historical development of the conception of "valuable paper" in Russia into five major stages. He found that, despite the existence of a relatively wide circulation of valuable papers, especially in the second half of the 19th century, Russian legislation before 1917 (the first stage) did not have a unified definition of valuable paper. The term was used, in both theoretical studies and legislation, but it covered a broad range of financial instruments such as stocks, bonds, government bonds, promissory notes, bills of exchange, etc. During the second stage, also, the legislation of the USSR did not have a unified definition of "valuable paper". After the end of the "new economic policy" (1922 - 1930) the stock exchanges and the securities markets in the USSR, with a very few exceptions, were abolished. And thus during the third stage (up to 1985), the use of valuable papers in practice was reduced to foreign economic relations (bills of exchange, stocks in enterprises outside the USSR) and to state bonds. Not surprisingly, there was still no unified definition of "valuable paper". After the beginning of Gorbachev's perestroika, a securities market began to re-appear in the USSR. However, the successful development of securities markets in the USSR was retarded by the absence of an appropriate regulatory framework. The first effort to improve the situation was the adoption of the Regulations on Valuable Papers, approved by resolution No. 590 of the Council of Ministers of the USSR, dated June 19, 1990. Section 1 of the Regulation contained the first statutory definition of "valuable paper" in the history of Russia. At the very beginning of the period of transition to a market economy, a number of acts contained different definitions of "valuable paper". This diversity clearly undermined the stability of the Russian securities market and did not achieve the goal of protecting the investor. The lack of unified criteria for the consideration of such non-standard financial instruments as "valuable papers" significantly contributed to the appearance of numerous fraudulent "pyramid" schemes that were outside of the regulatory scheme of Russia legislation. The situation was substantially improved by the adoption of the new Civil Code of the Russian Federation. According to Section 1 of Article 142 of the Civil Code, a valuable paper is a document that confirms, in compliance with an established form and mandatory requisites, certain material rights whose realisation or transfer are possible only in the process of its presentation. Finally, the recent Federal law No. 39 - FZ "On the Valuable Papers Market", dated April 22 1996, has also introduced the term "emission valuable papers". According to Article 2 of this Law, an "emission valuable paper" is any valuable paper, including non-documentary, that simultaneously has the following features: it fixes the composition of material and non-material rights that are subject to confirmation, cession and unconditional realisation in compliance with the form and procedure established by this federal law; it is placed by issues; and it has equal amount and time of realisation of rights within the same issue regardless of when the valuable paper was purchased. Thus the introduction of the conception of "emission valuable paper" became the starting point in the Russian federation's legislation for the differentiation between the legal regimes of "commercial papers" and "investment papers" similar to the Common Law approach. Moving now to the synchronic, comparative method of research, Mr. Pentsov notes that there are currently three major conceptions of "security" and, correspondingly, three approaches to its legal definition: the Common Law concept, the continental law concept, and the concept employed by Japanese Law. Mr. Pentsov proceeds to analyse the differences and similarities of all three, concluding that though the concept of "security" in the Common Law system substantially differs from that of "valuable paper" in the Continental Law system, nevertheless the two concepts are developing in similar directions. He predicts that in the foreseeable future the existing differences between these two concepts will become less and less significant. On the basis of his research, Mr. Pentsov arrived at the conclusion that the concept of "security" (and its equivalents) is not a static one. On the contrary, it is in the process of permanent evolution that reflects the introduction of new financial instruments onto the capital markets. He believes that the scope of the statutory definition of "security" plays an extremely important role in the protection of investors. While passing the Securities Act of 1933, the United States Congress determined that the best way to achieve the goal of protecting investors was to define the term "security" in sufficiently broad and general terms so as to include within the definition the many types of instruments that in the commercial world fall within the ordinary concept of "security' and to cover the countless and various devices used by those who seek to use the money of others on the promise of profits. On the other hand, the very limited scope of the current definition of "emission valuable paper" in the Federal Law of the Russian Federation entitled "On the Valuable Papers Market" does not allow the anti-fraud provisions of this law to be implemented in an efficient way. Consequently, there is no basis for the protection of investors. Mr. Pentsov proposes amendments which he believes would enable the Russian markets to become more efficient and attractive for both foreign and domestic investors.

Tolerance and Critical Thinking

Post-soviet countries are in the process of transformation from a totalitarian order to a democratic one, a transformation which is impossible without a profound shift in people's way of thinking. The group set themselves the task of determining the essence of this shift. Using a multidisciplinary approach, they looked at concrete ways of overcoming the totalitarian mentality and forming that necessary for an open democratic society. They studied the contemporary conceptions of tolerance and critical thinking and looked for new foundations of criticism, especially in hermeneutics. They then sought to substantiate the complementary relation between tolerance and criticism in the democratic way of thinking and to prepare a a syllabus for teaching on the subject in Ukrainian higher education. In a philosophical exploration of tolerance they began with relgious tolerance as its first and most important form. Political and social interests often lay at the foundations of religious intolerance and this implicitly comprised the transition to religious tolerance when conditions changed. Early polytheism was more or less indifferent to dogmatic deviations but monotheism is intolerant of heresies. The damage wrought by the religious wars of the Reformations transformed tolerance into a value. They did not create religious tolerance but forced its recognition as a positive phenomenon. With the weakening of religious institutions in the modern era, the purely political nature of many conflicts became evident and this stimulated the extrapolation of tolerance into secular life. Each historical era has certain acts and operations which may be interpreted as tolerant and these can be classified as to whether or not they are based on the conscious following of the principle of tolerance. This criterion requires the separation of the phenomenon of tolerance from its concept and from tolerance as a value. Only the conjunction of a concept of tolerance with a recognition of its value can transform it into a principle dictating a norm of conscious behaviour. The analysis of the contemporary conception of tolerance focused on the diversity of the concept and concluded that the notions used cannot be combined in the framework of a single more or less simple classification, as the distinctions between them are stimulated by the complexity of the realty considered and the variety of its manifestations. Notions considered in relation to tolerance included pluralism, respect and particular-universal. The rationale of tolerance was also investigated and the group felt that any substantiation of the principle of tolerance must take into account human beings' desire for knowledge. Before respecting or being tolerant of another person different from myself, I should first know where the difference lies, so knowledge is a necessary condition of tolerance.The traditional division of truth into scientific (objective and unique) and religious, moral, political (subjective and so multiple) intensifies the problem of the relationship between truth and tolerance. Science was long seen as a field of "natural" intolerance whereas the validity of tolerance was accepted in other intellectual fields. As tolerance eemrges when there is difference and opposition, it is essentially linked with rivaly and there is a a growing recognition today that unlimited rivalry is neither able to direct the process of development nor to act as creative matter. Social and economic reality has led to rivalry being regulated by the state and a natural requirement of this is to associate tolerance with a special "purified" form of rivalry, an acceptance of the actiivity of different subjects and a specification of the norms of their competition. Tolerance and rivalry should therefore be subordinate to a degree of discipline and the group point out that discipline, including self-discipline, is a regulator of the balance between them. Two problematic aspects of tolerance were identified: why something traditionally supposed to have no positive content has become a human activity today, and whether tolerance has full-scale cultural significance. The resolution of these questions requires a revision of the phenomenon and conception of tolerance to clarify its immanent positive content. This involved an investigation of the contemporary concept of tolerance and of the epistemological foundations of a negative solution of tolerance in Greek thought. An original soution to the problem of the extrapolation of tolerance to scientific knowledge was proposed based on the Duhem-Quine theses and conceptiion of background knowledge. In this way tolerance as a principle of mutual relations between different scientific positions gains an essential epistemological rationale and so an important argument for its own universal status. The group then went on to consider the ontological foundations for a positive solution of this problem, beginning with the work of Poincare and Reichenbach. The next aspect considered was the conceptual foundations of critical thinking, looking at the ideas of Karl Popper and St. Augustine and at the problem of the demarcation line between reasonable criticism and apologetic reasoning. Dogmatic and critical thinking in a political context were also considered, before an investigation of critical thinking's foundations. As logic is essential to critical thinking, the state of this discipline in Ukrainian and Russian higher education was assessed, together with the limits of formal-logical grounds for criticism, the role of informal logical as a basis for critical thinking today, dialectical logic as a foundation for critical thinking and the universality of the contemporary demand for criticism. The search for new foundations of critical thinking covered deconstructivism and critical hermeneutics, including the problem of the author. The relationship between tolerance and criticism was traced from the ancient world, both eastern and Greek, through the transitional community of the Renaissance to the industrial community (Locke and Mill) and the evolution of this relationship today when these are viewed not as moral virtues but as ordinary norms. Tolerance and criticism were discussed as complementary manifestations of human freedom. If the completeness of freedom were accepted it would be impossible to avoid recognition of the natural and legal nature of these manifestations and the group argue that critical tolerance is able to avoid dismissing such negative phenomena as the degradation of taste and manner, pornography, etc. On the basis of their work, the group drew up the syllabus of a course in "Logic with Elements of Critical Thinking, and of a special course on the "Problem of Tolerance".

Rapid climate change during the Weichselian Lateglacial in Ireland: Chironomid-inferred summer temperatures from Fiddaun, Co. Galway

A lacustrine sediment core from Fiddaun, western Ireland was studied to reconstruct summer temperature changes during the Weichselian Lateglacial. This site is located close to the Atlantic Ocean; and so is potentially sensitive to climatic changes associated with changes in ocean circulation. The record, comprising the end of the Weichselian Pleniglacial to the early Holocene, was analysed for fossil chironomids, lithology, and oxygen and carbon isotopes in the sedimentary carbonates. These proxies clearly show rapid warming at the onset of the Lateglacial Interstadial, relatively high summer temperatures during the Interstadial, pronounced cooling during the Younger Dryas, and subsequent warming at the transition to the Holocene. Chironomid-inferred mean July air temperatures for the Interstadial are ~12.5–14.5 °C, ~7.5 °C for the Younger Dryas, and ~15.0 °C for the early Holocene. Furthermore, this research provides evidence for at least two cold events during the Interstadial. These more moderate temperature oscillations can be correlated to Greenland Interstadial events 1b and 1d, on the basis of the age-depth model for the Fiddaun sequence. Based on multiple proxies, the first cold oscillation (GI-1d) was the more severe of the two in Ireland.

Climate warming and vegetation response after Heinrich event 1 (16 700–16 000 cal yr BP) in Europe south of the Alps

Chironomids preserved in a sediment core from Lago di Origlio (416 m a.s.l.), a lake in the foreland of the Southern Swiss Alps, allowed quantitative reconstruction of Late Glacial and Early Holocene summer temperatures using a combined Swiss–Norwegian temperature inference model based on chironomid assemblages from 274 lakes. We reconstruct July air temperatures of ca. 10 °C between 17 300 and 16 000 cal yr BP, a rather abrupt warming to ca. 12.0 °C at ca. 16 500–16 000 cal yr BP, and a strong temperature increase at the transition to the Bølling/Allerød interstadial with average temperatures of about 14 °C. During the Younger Dryas and earliest Holocene similar temperatures are reconstructed as for the interstadial. The rather abrupt warming at 16 500–16 000 cal yr BP is consistent with sea-surface temperature as well as speleothem records, which indicate a warming after the end of Heinrich event 1 (sensu stricto) and before the Bølling/Allerød interstadial in southern Europe and the Mediterranean Sea. Pollen records from Origlio and other sites in southern Switzerland and northern Italy indicate an early reforestation of the lowlands 2000–1500 yr prior to the large-scale afforestation of Central Europe at the onset of the Bølling/Allerød period at ca. 14 700–14 600 cal yr BP. Our results suggest that these early afforestation processes in the formerly glaciated areas of northern Italy and southern Switzerland have been promoted by increasing temperatures.

Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C-reactive protein, and D-dimer

BACKGROUND: Elevated plasma levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimer belong to the biological alterations of the "frailty syndrome," defining increased vulnerability for diseases and mortality with aging. We hypothesized that, compatible with premature frailty, chronic stress and age are related in predicting inflammation and coagulation activity in Alzheimer caregivers. METHODS: Plasma IL-6, CRP, and D-dimer levels were measured in 170 individuals (mean age 73 +/- 9 years; 116 caregivers, 54 noncaregiving controls). Demographic factors, diseases, drugs, and lifestyle variables potentially affecting inflammation and coagulation were obtained by history and adjusted for as covariates in statistical analyses. RESULTS: Caregivers had higher mean levels of IL-6 (1.38 +/- 1.42 vs 1.00 +/- 0.92 pg/mL, p =.032) and of D-dimer (723 +/- 530 vs 471 +/- 211 ng/mL, p <.001) than controls had. CRP levels were similar between groups (p =.44). The relationship between caregiver status and D-dimer was independent of covariates (p =.037) but affected by role overload. Age accounted for much of the relationship with IL-6. After controlling for covariates, the interaction between caregiver status and age was significant for D-dimer (beta =.20, p =.029) and of borderline significance for IL-6 (beta =.17, p =.090). Post hoc regression analyses indicated that, among caregivers, age was significantly correlated with both D-dimer (beta =.50, p <.001) and IL-6 (beta =.38, p =.001). Among controls, however, no significant relationship was observed between age and either D-dimer or IL-6. CONCLUSIONS: The interaction between caregiving status and age for D-dimer and IL-6 suggests the possibility that older caregivers could be at risk of a more rapid transition to the frailty syndrome and clinical manifestations of cardiovascular diseases.

INVESTIGATING THE ROLE OF THE CONTACT LINE IN HETEROGENEOUS NUCLEATION WITH HIGH SPEED IMAGING

While nucleation of solids in supercooled liquids is ubiquitous [15, 65, 66], surface crystallization, the tendency for freezing to begin preferentially at the liquid-gas interface, has remained puzzling [74, 18, 68, 69, 51, 64, 72, 16]. Here we employ high-speed imaging of supercooled water drops to study the phenomenon of heterogeneous surface crystallization. Our geometry avoids the "point-like contact" of prior experiments by providing a simple, symmetric contact line (triple line defined by the substrate-liquid-air interface) for a drop resting on a homogeneous silicon substrate. We examine three possible mechanisms that might explain these laboratory observations: (i) Line Tension at the triple line, (ii) Thermal Gradients within the droplets and (iii) Surface Texture. In our first study we record nearly perfect spatial uniformity in the immersed (liquid-substrate) region and, thereby, no preference for nucleation at the triple line. In our second study, no influence of thermal gradients on the preference for freezing at the triple line was observed. Motivated by the conjectured importance of line tension (τ) [1, 66] for heterogeneous nucleation, we also searched for evidence of a transition to surface crystallization at length scales on the order of δ ∼ τ/σ, where σ is the surface tension [14]; poorly constrained τ [49] leads to δ ranging from microns to nanometers. We demonstrate that nano-scale texture causes a shift in the nucleation to the three-phase contact line, while micro-scale texture does not. The possibility of a critical length scale has implications for the effectiveness of nucleation catalysts, including formation of ice in atmospheric clouds [7].

Long-term maternal imprinting of the specific B cell repertoire by maternal antibodies

Maternal antibodies protect newborns whilst they are immunologically immature. This study shows that maternal antibodies can also shape the B cell repertoire of the offspring long after the maternal antibodies themselves become undetectable. V(H)DJ(H) gene-targeted (VI10) mice expressing a heavy chain specific for vesicular stomatitis virus (VSV) produce a 20-fold increased spontaneous titer of VSV-neutralizing antibodies. When transferred from mother to offspring, these antibodies prevented accumulation of Ag-specific transitional type 2 and marginal zone B cells with an activated phenotype and favored selection to the B cell follicles. This effect was B cell-intrinsic and lasted up to adulthood. The pups nursed by mothers producing specific antibodies developed higher endogenous antibody titers of this specificity which perpetuated the effects of specific B cell selection into the mature follicular compartment, presumably by blocking auto-Ag-dependent development of transitional type 2 B cells in the spleen. This repertoire change was functional, as following infection of adult mice with VSV, those pups that had received specific maternal antibodies as neonates had increased pre-immune titers and mounted strong early IgG neutralizing antibodies.