Modeling the initiation of others into injection drug use, using data from 2,500 injectors surveyed in Scotland during 2008-2009

The prevalence of injection drug use has been of especial interest for assessment of the impact of blood-borne viruses. However, the incidence of injection drug use has been underresearched. Our 2-fold aim in this study was to estimate 1) how many other persons, per annum, an injection drug user (IDU) has the equivalent of full responsibility (EFR) for initiating into injection drug use and 2) the consequences for IDUs' replacement rate. EFR initiation rates are strongly associated with incarceration history, so that our analysis of IDUs' replacement rate must incorporate when, in their injecting career, IDUs were first incarcerated. To do so, we have first to estimate piecewise constant incarceration rates in conjunction with EFR initiation rates, which are then combined with rates of cessation from injecting to model IDUs' replacement rate over their injecting career, analogous to the reproduction number of an epidemic model. We apply our approach to Scotland's IDUs, using over 2,500 anonymous injector participants who were interviewed in Scotland's Needle Exchange Surveillance Initiative during 2008-2009. Our approach was made possible by the inclusion of key questions about initiations. Finally, we extend our model to include an immediate quit rate, as a reasoned compensation for higher-than-expected replacement rates, and we estimate how high initiates' quit rate should be for IDUs' replacement rate to be 1

Modeling the initiation of others into injection drug use, using data from 2,500 injectors surveyed in Scotland during 2008-2009

The prevalence of injection drug use has been of especial interest for assessment of the impact of blood-borne viruses. However, the incidence of injection drug use has been underresearched. Our 2-fold aim in this study was to estimate 1) how many other persons, per annum, an injection drug user (IDU) has the equivalent of full responsibility (EFR) for initiating into injection drug use and 2) the consequences for IDUs' replacement rate. EFR initiation rates are strongly associated with incarceration history, so that our analysis of IDUs' replacement rate must incorporate when, in their injecting career, IDUs were first incarcerated. To do so, we have first to estimate piecewise constant incarceration rates in conjunction with EFR initiation rates, which are then combined with rates of cessation from injecting to model IDUs' replacement rate over their injecting career, analogous to the reproduction number of an epidemic model. We apply our approach to Scotland's IDUs, using over 2,500 anonymous injector participants who were interviewed in Scotland's Needle Exchange Surveillance Initiative during 2008-2009. Our approach was made possible by the inclusion of key questions about initiations. Finally, we extend our model to include an immediate quit rate, as a reasoned compensation for higher-than-expected replacement rates, and we estimate how high initiates' quit rate should be for IDUs' replacement rate to be 1

Tracing climate and human-driven erosional activity in the Transylvania lowlands (Central-Eastern Europe) during the Holocene

Erosion is a complex geomorphological process controlled by climate, soil and vegetation characteristics in addition to land-use. However, the interplay of these drivers is not fully understood. Here we present a 11.8 ka multi-proxy record of geochemical, mineral magnetic and grain size analyses from Lake Stiucii, in the Transylvania lowlands (CE Europe) documenting past erosional activity and the drivers of landscape change. We identify three major phases in the site’s development. The first, a lacustrine phase (11.8–10.9 cal ka BP), is characterised by open water conditions with significant river inflow and depicts a period of greater erosion under a less developed catchment vegetation cover. Between 10.9 and 4.6 cal ka BP, the lake became a wetland characterised by shallow water with a reduced drainage network under warmer climate and/or reduced rainfall. From 4.6 cal ka BP, a second lacustrine phase developed driven by enhanced stream flow and sediment input subsequently accelerated by land use change. On a millennial scale, the two significant changes in the lake-catchment system and erosion regime at 10.9 and 4.6 cal ka BP may reflect a response to fluctuations in large-scale atmospheric circulation patterns. The eight short-term erosional events identified at 10.6, 7.8 cal ka BP, between 4.4–4.1, 3.5, 3.0–2.5, 1.9, 1.5, 1.1–0.8 cal ka BP, overlap well-known climate events. However, from 4.6 cal ka BP the climate-landscape relationship is amplified by rising anthropogenic impacts. Our data provide critical information on the paleoenvironmental evolution of CE Europe’s lowlands and facilitate discussion of the effects of millennial and centennial climatic shifts as expressed in the local environment

Drugs-related death soon after hospital discharge among drug treatment clients in Scotland:record linkage, validation and investigation of risk factors.

We validate that the 28 days after hospital-discharge are high-risk for drugs-related death (DRD) among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD), including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29-90 days, 91 days-1 year, >1 year since most recent hospital discharge versus 'never admitted'. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0-1 versus 2+ days), and main discharge-diagnosis. We confirm SDMD clients' high DRD-rate soon after hospital-discharge in 2006-2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever-injectors for 222/290. Hospital-discharge remains a period of increased DRD-vulnerability in 2006-2010, as in 1996-2006, especially for those with a history of injecting

Reconstructing the history of heavy metal pollution in the southern Pennines from the sedimentary record of reservoirs: methods and preliminary results

Although the southern Pennine uplands have experienced industrially derived heavy metal pollution for almost two hundred years, an historical analysis of its depositional records has not yet been undertaken. The area has no natural lakes but has many reservoirs, and despite the potential for sediment disturbance due to fluctuating water levels, reservoir sediments can be used as a record of heavy metal pollution. A methodology for the selection of reservoirs with undisturbed sedimentary records, and the verification of sediment stratigraphy is proposed. Preliminary results of metal analysis from the Howden reservoir indicate trace metal contamination with Zn > Pb > Cr > Ni = Cu

Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes

The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA

Climate and land-use as the main drivers of recent environmental change in a mid-altitude mountain lake, Romanian Carpathians

Recent decades have been marked by unprecendented environmental changes which threaten the integrity of freshwater systems and their ecological value. Although most of these changes can be attributed to human activities, disentagling natural and anthropogenic drivers remains a challenge. In this study, surface sediments from Lake Ighiel, a mid-altitude site in the Carpathian Mts (Romania) were investigated following high-resolution sedimentological, geochemical, environmental magnetic and diatom analyses supported by historical cartographic and documentary evidence. Our results suggest that between 1920 and 1960 the study area experienced no significant anthropogenic impact. An excellent correspondence is observed between lake proxy responses (e.g., growth of submerged macrophytes, high detrital input, shifts in diatom assemblages) and parameters tracking natural hydroclimate variability (e.g., temperature, NAO). This highlights a dominant natural hydroclimatic control on the lacustrine system. From 1960 however, the depositional regime shifted markedly from laminated to homogenous clays; since then geochemical and magnetic data document a trend of significant (and on-going) subsurface erosion across the catchment. This is paralleled by a shift in lake ecosystem conditions denoting a strong response to an intensified anthropogenic impact, mainly through forestry. An increase in detrital input and marked changes in the diatom community are observed over the last three decades, alongside accelerated sedimentation rates following enhanced grazing and deforestation in the catchment. Recent shifts in diatom assemblages may also reflect forcing from atmospheric nitrogen (N) deposition, a key recent drive of diatom community turnover in mountain lakes. In general, enhanced human pressure alongside intermittent hydroclimate forcing drastically altered the landscape around Lake Ighiel and thus, the sedimentation regime and the ecosystem’s health. However, paleoenvironmental signals tracking natural hydroclimate variability are also clearly discernible in the proxy data. Our work illustrates the complex link between the drivers of catchment-scale impacts on one hand, and lake proxy responses on the other, highlighting the importance of an integrated historical and palaeolimnological approach to better assess lake system changes

Orbits and phase transitions in the multifractal spectrum

We consider the one dimensional classical Ising model in a symmetric dichotomous random field. The problem is reduced to a random iterated function system for an effective field. The D_q-spectrum of the invariant measure of this effective field exhibits a sharp drop of all D_q with q < 0 at some critical strength of the random field. We introduce the concept of orbits which naturally group the points of the support of the invariant measure. We then show that the pointwise dimension at all points of an orbit has the same value and calculate it for a class of periodic orbits and their so-called offshoots as well as for generic orbits in the non-overlapping case. The sharp drop in the D_q-spectrum is analytically explained by a drastic change of the scaling properties of the measure near the points of a certain periodic orbit at a critical strength of the random field which is explicitly given. A similar drastic change near the points of a special family of periodic orbits explains a second, hitherto unnoticed transition in the D_q-spectrum. As it turns out, a decisive role in this mechanism is played by a specific offshoot. We furthermore give rigorous upper and/or lower bounds on all D_q in a wide parameter range. In most cases the numerically obtained D_q coincide with either the upper or the lower bound. The results in this paper are relevant for the understanding of random iterated function systems in the case of moderate overlap in which periodic orbits with weak singularity can play a decisive role.Comment: The article has been completely rewritten; the title has changed; a section about the typical pointwise dimension as well as several references and remarks about more general systems have been added; to appear in J. Phys. A; 25 pages, 11 figures, LaTeX2

A Complete Expression Profile of Matrix-Degrading Metalloproteinases in Dupuytren’s Disease

Dupuytren’s disease (DD) is a common fibrotic condition of the palmar fascia, leading to deposition of collagen-rich cords and finger contractions. The metzincin superfamily contains key enzymes in the turnover of collagen and other extracellular matrix macromolecules. A number of broad-spectrum matrix metalloproteinase inhibitors, used in cancer clinical trials, caused side effects of DD-like contractures. We tested the hypothesis that changes in the expression of specific metalloproteinases underlie or contribute to the fibrosis and contracture seen in DD. We collected tissue from patients with DD and used normal palmar fascia as a control. We profiled the expression of the entire matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMP), and a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) gene families in these tissues using real-time reverse-transcription polymerase chain reaction. A number of metalloproteinases and inhibitors are regulated in DD. The expression of 3 key collagenases, MMP1, MMP13, and MMP14 is increased significantly in the DD nodule, as is the expression of the collagen biosynthetic enzyme ADAMTS14. The expression of MMP7, an enzyme with broad substrate specificity, is increased in the DD nodule and remains equally expressed in the DD cord. TIMP1 expression is increased significantly in DD nodule compared with normal palmar fascia. This study measured the expression of all MMP, ADAMTS, and TIMP genes in DD. Contraction and fibrosis may result from: (1) increased collagen biosynthesis mediated by increased ADAMTS-14; (2) an increased level of TIMP-1 blocking MMP-1– and MMP-13–mediated collagenolysis; and (3) contraction enabled by MMP-14–mediated pericellular collagenolysis (and potentially MMP-7), which may escape inhibition by TIMP-1. The complete expression profile will provide a knowledge-based approach to novel therapeutics targeting these genes

Impacts of Climate Change on indirect human exposure to pathogens and chemicals from agriculture

Objective: Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. Data sources: In this review, we used expert input and considered literature on climate change ; health effects resulting from exposure to pathogens and chemicals arising from agriculture ; inputs of chemicals and pathogens to agricultural systems ; and human exposure pathways for pathogens and chemicals in agricultural systems. Data synthesis: We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment ; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems ; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Conclusions: Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes