Search

Employee alcohol and other drug use can negatively impact the workplace, resulting in absenteeism, reduced productivity, high turnover, and worksite safety issues. As the workplace can influence employee substance use through environmental and cultural factors, it also presents a key opportunity to deliver interventions, particularly to employees who may not otherwise seek help. This is a systematic review of workplace-based interventions for the prevention and treatment of problematic substance use. Five databases were searched for efficacy, effectiveness and/or cost-effectiveness studies and reviews published since 2010 that measured use of psychoactive substances (i.e., alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, and stimulants) as a primary or secondary outcome, in employees aged over 18. Thirty-nine articles were identified, 28 describing primary research and 11 reviews, most of which focused solely on alcohol use. Heterogeneity between studies with respect to intervention and evaluation design limited the degree to which findings could be synthesized, however, there is some promising evidence for workplace-based universal health promotion interventions, targeted brief interventions, and universal substance use screening. The few studies that examined implementation in the workplace revealed specific barriers including lack of engagement with e-health interventions, heavy use and reluctance to seek help amongst male employees, and confidentiality concerns. Tailoring interventions to each workplace, and ease of implementation and employee engagement emerged as facilitators. Further high-quality research is needed to examine the effectiveness of workplace substance use testing, Employee Assistance Programs, and strategies targeting the use of substances other than alcohol in the workplace.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227598, PROSPERO [CRD42021227598].

Stepped-care is a commonly recommended and implemented care model across health care domains, including substance use. Despite their presumed efficient allocation of treatment resources, a current and robust evidence synthesis is needed on the efficacy, effectiveness and cost-effectiveness of stepped-care for substance use.This systematic review analyzed articles describing evaluations of stepped-care models that measured the use of acutely psychoactive substances (i.e., alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, and stimulants) as a primary or secondary outcome, in participants over 18 years old. The analysis investigated model and participant characteristics associated with treatment outcomes.The study team conducted a search of five databases of literature (PsychINFO, MEDLINE, Embase, Cochrane Library and Scopus) published between January 1, 2010, and November 1, 2020. The search yielded 1051 unique articles, 19 of which were included in the analysis. The studies had considerable variability in sample sizes (n = 18-2310), time to follow-up (4.5 months to 3 years), and retention rates (35.1-100 %). Studies examined outcomes for either alcohol alone (n = 9), alcohol and other drug use (n = 9), or drug use alone (n = 1). Most studies (n = 13;) were rated as good quality. Three (15.8 %) were rated as fair and three (15.8 %) were rated as poor quality. The evidence regarding the efficacy, effectiveness and cost-effectiveness of stepped-care approaches is limited, but four of seven studies found that adaptive-care interventions delivered in the context of other systemic interventions produced greater benefit than control conditions in relation to at least one alcohol-related outcome. We have insufficient evidence to determine whether the modes or intensity of interventions included in the models, or decision rules used to step people up or down to differing levels of care, have an impact on outcome.Heterogeneity between studies with regard to model and evaluation design limited the degree to which the analysis could draw robust conclusions. Sample recruitment and statistical power are particular challenges, and the field needs more innovative evaluation designs to assess the efficacy, effectiveness, and cost-effectiveness of stepped-care models.

Adaptive reward-related decision making often requires accurate and detailed representation of potential available rewards. Environmental reward-predictive stimuli can facilitate these representations, allowing one to infer which specific rewards might be available and choose accordingly. This process relies on encoded relationships between the cues and the sensory-specific details of the rewards they predict. Here, we interrogated the function of the basolateral amygdala (BLA) and its interaction with the lateral orbitofrontal cortex (lOFC) in the ability to learn such stimulus-outcome associations and use these memories to guide decision making. Using optical recording and inhibition approaches, Pavlovian cue-reward conditioning, and the outcome-selective Pavlovian-to-instrumental transfer (PIT) test in male rats, we found that the BLA is robustly activated at the time of stimulus-outcome learning and that this activity is necessary for sensory-specific stimulus-outcome memories to be encoded, so they can subsequently influence reward choices. Direct input from the lOFC was found to support the BLA in this function. Based on prior work, activity in BLA projections back to the lOFC was known to support the use of stimulus-outcome memories to influence decision making. By multiplexing optogenetic and chemogenetic inhibition we performed a serial circuit disconnection and found that the lOFC→BLA and BLA→lOFC pathways form a functional circuit regulating the encoding (lOFC→BLA) and subsequent use (BLA→lOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.

Adaptive reward-related decision making often requires accurate and detailed representation of potential available rewards. Environmental reward-predictive stimuli can facilitate these representations, allowing one to infer which specific rewards might be available and choose accordingly. This process relies on encoded relationships between the cues and the sensory-specific details of the reward they predict. Here we interrogated the function of the basolateral amygdala (BLA) and its interaction with the lateral orbitofrontal cortex (lOFC) in the ability to learn such stimulus-outcome associations and use these memories to guide decision making. Using optical recording and inhibition approaches, Pavlovian cue-reward conditioning, and an outcome-selective Pavlovian-to-instrumental transfer (PIT) test in male rats, we found that the BLA is robustly activated at the time of stimulus-outcome learning and that this activity is necessary for sensory-specific stimulus-outcome memories to be encoded, so that they can subsequently influence reward choices. Direct input from the lOFC was found to support the BLA in this function. Based on prior work, activity in BLA projections back to the lOFC was known to support the use of stimulus-outcome memories to influence decision making. By multiplexing optogenetic and chemogenetic inhibition to perform a serial circuit disconnection, we found that activity in lOFC[->]BLA projections regulates the encoding of the same components of the stimulus-outcome memory that are later used to allow cues to guide choice via activity in BLA[->]lOFC projections. Thus, the lOFC[->]BLA[->]lOFC circuit regulates the encoding (lOFC[->]BLA) and subsequent use (BLA[->]lOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.

Predictive learning exerts a powerful influence over choice between instrumental actions. Nevertheless, how this learning is encoded in a sufficiently stable manner to influence choices that can occur much later in time is unclear. Here, we report that the basolateral amygdala (BLA) encodes predictive learning and establishes the memory necessary for future choices by driving the accumulation of delta-opioid receptors (DOPRs) on the somatic membrane of cholinergic interneurons in the nucleus accumbens shell (NAc-S). We found that the BLA controls DOPR accumulation via its influence on substance P release in the NAc-S, and that although DOPR accumulation is not necessary for predictive learning per se, it is necessary for the influence of this learning on later choice between actions. This study uncovers, therefore, a novel GPCR-based form of memory that is established by predictive learning and is necessary for such learning to guide the selection and execution of specific actions.

Predictive learning exerts a powerful influence over choice between instrumental actions. Nevertheless, how this learning is encoded in a sufficiently stable manner to influence choices that can occur much later in time is unclear. Here, we report that the basolateral amygdala (BLA) encodes predictive learning and establishes the memory necessary for future choices by driving the accumulation of delta-opioid receptors (DOPR) on the somatic membrane of cholinergic interneurons in the nucleus accumbens shell (NAc-S). We found that the BLA controls DOPR accumulation via its influence on substance P release in the NAc-S and that, although DOPR accumulation is not necessary for predictive learning per se, it is necessary for the influence of this learning on later choice between actions. This study uncovers, therefore, a novel GPCR-based form of memory that is established by predictive learning and is necessary for such learning to guide the selection and execution of specific actions.

Summary The roles of the microbiome and innate immunity in the pathogenesis of multiple sclerosis (MS) remain unclear. We have previously documented abnormally low levels of a microbiome-derived Toll-like receptor (TLR)2-stimulating bacterial lipid in the blood of MS patients and postulated that this is indicative of a deficiency in the innate immune regulating function of the microbiome in MS. We postulated further that the resulting enhanced TLR2 responsiveness plays a critical role in the pathogenesis of MS. As proof-of-concept, we reported that decreasing systemic TLR2 responsiveness by administering very low-dose TLR2 ligands attenuated significantly the mouse model of MS, experimental autoimmune encephalomyelitis. Studies of Toll-like receptor responses in patients with MS have been conflicting. Importantly, most of these investigations have focused on the response to TLR4 ligation and few have characterized TLR2 responses in MS. In the present study, our goal was to characterize TLR2 responses of MS patients using multiple approaches. Studying a total of 26 MS patients and 32 healthy controls, we now document for the first time that a large fraction of MS patients (50%) demonstrate enhanced responsiveness to TLR2 stimulation. Interestingly, the enhanced TLR2 responders include a significant fraction of those with progressive forms of MS, a subset of patients considered unresponsive to adaptive immune system-targeting therapies. Our results suggest the presence of a pathologically relevant TLR2 related innate immune abnormality in patients with both relapsing–remitting and progressive MS. These findings may have significant implications for understanding the role of innate immunity in the pathogenesis of MS.

Contemporary theories emphasize the involvement of the endogenous opioid system in assigning hedonic values to rewards. Although earlier research supports this view, recent findings suggest that opioids play a larger and more complex role in reward processes than these theories suggest. For example, opioid activity in the basolateral amygdala is required for encoding incentive learning, a process by which the value of goal-directed actions is updated. Outside the amygdala, opioid receptors in the ventral striatum have been found to promote choice between different courses of action. Specifically, μ opioid receptors in the nucleus accumbens core and δ opioid receptors in the nucleus accumbens shell have been reported to mediate distinct aspects of incentive motivation; the core regulating the effect of experienced reward and the shell of predicted reward on choice. In both cases, the involvement of opioid receptors was restricted to the time of choice, although changes in their expression pattern could be observed prior to that point. This time-restricted involvement of opioid receptor-related processes is consistent with the view that opioids in the nucleus accumbens are central components of the limbic-motor interface, integrating reward-related information with instrumental learning to guide decision-making, particularly the selection and execution of goal-directed actions. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2

The clean development mechanism (CDM) has been a leading international carbon market and a driving force for sustainable development. But the eruption of controversy over offsets from Chinese wind power in 2009 exposed cracks at the core of how carbon credits are verified in the developing economies. The Chinese wind controversy therefore has direct implications for the design and negotiation of any successor to the Kyoto Protocol or future market-based carbon regimes. In order for carbon markets to avoid controversy and function effectively, the lessons from the Chinese wind controversy should be used to implement key reforms in current and future carbon policy design. The paper examines the application of additionality in the Chinese wind power market and draws implications for the design of effective global carbon offset policy. It demonstrates the causes of the wind power controversy, highlights underlying structural flaws, in how additionality is applied in China, the Offsetters' Paradox, and charts a reform path that can strengthen the credibility of global carbon markets.

The conservation of prairie dogs in the Western United States is contentious, as prairie dogs are often considered pests. This research addresses the ecological and social outlook for prairie dog colonies in Denver, Colorado. Remote sensing analysis was applied to identify potential locations for colony reintroduction. To assess the social outlook, knowledge and attitudinal surveys were distributed to residents living near existing colonies and potential colony sites. Statistical analysis of responses provided insight into relationships amongst ecological knowledge, access to educational literature, demographics, and attitudes toward prairie dogs. Results indicated that women view prairie dogs more favorably than men; ecological knowledge was strongly associated with favorableness toward prairie dogs; and residents living near existing colonies were more favorable toward prairie dogs. We conclude that prairie dogs have the potential to be sustained in Denver. This study may help wildlife managers in targeting neighborhood-level education efforts to specific demographics and (mis) conceptions. Refereed/Peer-reviewed

A comprehensive Code of Ethics for the members of the American Association of Physicists in Medicine (AAPM) is presented as the report of Task Group 109 which consolidates previous AAPM ethics policies into a unified document. The membership of the AAPM is increasingly diverse. Prior existing AAPM ethics polices were applicable specifically to medical physicists, and did not encompass other types of members such as health physicists, regulators, corporate affiliates, physicians, scientists, engineers, those in training, or other health care professionals. Prior AAPM ethics policies did not specifically address research, education, or business ethics. The Ethics Guidelines of this new Code of Ethics have four major sections: professional conduct, research ethics, education ethics, and business ethics. Some elements of each major section may be duplicated in other sections, so that readers interested in a particular aspect of the code do not need to read the entire document for all relevant information. The prior Complaint Procedure has also been incorporated into this Code of Ethics. This Code of Ethics (PP 24-A) replaces the following AAPM policies: Ethical Guidelines for Vacating a Position (PP 4-B); Ethical Guidelines for Reviewing the Work of Another Physicist (PP 5-C); Guidelines for Ethical Practice for Medical Physicists (PP 8-D); and Ethics Complaint Procedure (PP 21-A). The AAPM Board of Directors approved this Code or Ethics on July 31, 2008.

BACKGROUND. We conducted a phase 2, multicenter, open-label study of erlotinib plus bevacizumab in patients with malignant pleural mesothelioma who had previously received 1 prior chemotherapy regimen. These agents have activity in non–small cell lung cancer, but their role in mesothelioma is unclear. The primary endpoint is response rate. Secondary endpoints include time to progression, survival, and toxicity. METHODS. Eligible patients with mesothelioma who had previously received 1 chemotherapy regimen were treated with erlotinib 150 mg per os daily and bevacizumab 15 mg/kg administered intravenously on Day 1 of a 21-day cycle. Treatment continued until disease progression or development of significant toxicity. Tumor response was assessed after every 2 cycles using previously established mesothelioma response criteria from Byrne and Nowak. RESULTS. Twenty-four eligible patients initiated therapy with erlotinib and bevacizumab between February 2004 and October 2006. There were no complete or partial responses, although 12 patients achieved stable disease for at least 2 cycles of treatment. The median time to progression was 2.2 months (95% confidence interval [CI], 1.4 months-5.9 months). The median survival was 5.8 months (95% CI, 2.8 months-10.1 months). The most common toxicities were rash and diarrhea. There were no treatment-related deaths, intracranial bleeding, or hemoptysis. CONCLUSIONS. The combination of erlotinib and bevacizumab was tolerated reasonably well, but there was no evidence of radiographic response. This study demonstrates the feasibility of conducting trials in mesothelioma patients who have failed first-line therapy. More therapeutic studies with effective agents are needed for these patients. Cancer 2008. © 2008 American Cancer Society.

The Washington metropolitan area was closely examined to understand how these regional preparedness structures have been organized, implemented, and governed, as well as to assess the likely impact of such regional structures on public health preparedness and public health systems more generally. It was found that no single formal regional structure for the public health system exists in the Washington metropolitan area, although the region is designated by the Department of Homeland Security as the National Capital Region (NCR). In fact, the vast majority of preparedness planning and response activities in this area are the result of voluntary self-organization through both governmental and nongovernmental organizations. Some interviewed felt that this was an optimal arrangement, as personal relationships prove crucial in responding to a public health emergency and an informal response is often more timely than a formal response. The biggest challenge for public health preparedness in the NCR is incorporating all federal government agencies in the area in NCR preparedness planning.

Coal has been the world's fastest-growing energy source in absolute terms for over a decade. Coal also emits more CO2 than any other fossil fuel and contributes to serious air pollution problems in many regions of the world. If we hope to satisfy the demand for affordable energy in emerging economies while protecting the environment, we need to develop a keen understanding of the market that supplies coal. This book offers an in-depth analysis of the key producers and consumers that will most influence coal production, transport, and use in the future. By exploring how countries such as China, India, Indonesia, Australia and South Africa have developed their respective coal industries - and how these industries link together through the international coal trade - experts shed light on how the global coal market may evolve, and the economic and environmental implications. This book is the most comprehensive treatment of these topics to date and will appeal to a wide readership, including scholars and practitioners working on energy economics and policy.

Objectives To discuss the mechanism by which epidermal growth factor receptor (EGFR)-targeted agents work, the resulting cutaneous toxicities, the pathophysiology of the unique rash associated with these agents, and the management of these skin problems. Data Sources Published scientific papers, review articles, book chapters, and clinical experiences. Conclusion These new targeted agents result in unique cutaneous toxicities. Researchers and clinicians have made numerous suggestions for managing the various side effects, although there is currently no research to guide evidence-based practice. Implications for Nursing Practice With any new treatment option, it is imperative that nurses understand how agents work to enrich their own knowledge base, as well as have a strong foundation for patient education. It is important that nurses understand potential side effects of these agents, know of possible interventions, and participate in research to identify effective interventions.

This paper reports on a qualitative, critical study into the lives of relatives and partners of people living with enduring effects of schizophrenia. A review of the literature showed that caregivers and relatives of sufferers were seldom asked about their experiences, instead they were subject to blame or criticism regarding their parental or caregiving practices. Caregivers of people with schizophrenia were interviewed in order to reveal their experience of caring for their kin after a medication change to atypical neuroleptics. The interview analysis was compared with mental health professional literature, using a Foucauldian approach to reveal the operation of language and power in the positioning of caregivers. This analysis was then compared to the talk of the caregivers. Similarities and differences in their ways of talking about caring were identified. Caregivers spoke of protracted periods of time before the establishment of a definite diagnosis, ambivalence about medication and 'never giving up'. The paper concludes that life for caregivers is constituted as doubly problematic, experiencing stigma personally and vicariously through their kin.

The home is getting more and more connected. Smart sensors are monitoring systems and activities and, in many cases, working together to enhance the efficiency and capability of your home. It's the dream of the Internet of Things (IoT), and it's becoming a reality in our homes. But the smart home can become a security nightmare because every connected device is a new potential entry point for cyberattacks. Criminals are looking for vulnerabilities to gain access to connected devices in the home to steal personal data and even break into the premises. Once inside, they can quickly pivot to target service provider networks and content and mount larger-scale attacks This paper looks at the common attack scenarios and presents an approach to mitigate this challenge, which, if unchecked, will result in a lower adoption rate by consumers.

// David M. Jackman 1, 2, * , Leigh A. Cioffredi 4 , Lorraine Jacobs 5 , Farhana Sharmeen 1 , Linda K. Morse 1 , Joan Lucca 1 , Scott R. Plotkin 2, 6 , Paul J. Marcoux 1, 2 , Michael S. Rabin 1, 2 , Thomas J. Lynch 7, 8 , Bruce E. Johnson 1, 2 , Santosh Kesari 3, * 1 Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA 2 Harvard Medical School, Boston, MA, USA 3 Department of Neurosciences, Translational Neuro-Oncology Laboratories, Moores UCSD Cancer Center, University of California, San Diego, La Jolla CA, USA 4 Georgetown University School of Medicine, Washington, DC, USA 5 Eurofins Medinet B.V., Breda, The Netherlands 6 Stephen E. & Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA 7 Smilow Cancer Hospital at Yale-New Haven, Yale Cancer Center, New Haven, CT, USA 8 Yale University, New Haven, CT, USA * These authors have contributed equally to this work Correspondence to: David M. Jackman, e-mail: djackman@partners.org Santosh Kesari, e-mail: skesari@ucsd.edu Keywords: non-small cell lung carcinoma, epidermal growth factor receptor, meningeal carcinomatosis, kinase inhibitors Received: September 20, 2014 Accepted: December 09, 2014 Published: February 25, 2015 ABSTRACT Introduction: There are few effective treatment options for leptomeningeal metastasis (LM) in non-small-cell lung cancer (NSCLC). This study assessed the feasibility of high-dose gefitinib in patients with LM from NSCLC harboring EGFR mutations or prior systemic response to EGFR-TKI. Methods: This phase I open-label trial of a novel gefitinib dosing schedule employed a 3+3 design. Eligible NSCLC patients with LM had known EGFR mutations and/or prior response to EGFR-TKI. Patients alternated 2 weeks of high-dose daily gefitinib (dose levels: 750 mg, 1000 mg, 1250 mg) with 2 weeks of maintenance therapy (500 mg daily). Primary endpoints were safety and toxicity. Secondary endpoints included overall survival (OS), neurological progression-free survival, radiological response, and cytological response in cerebrospinal fluid (CSF). Results: Seven patients were treated: 3 at 750 mg dose level, 4 at 1000 mg dose level. There were no DLTs at the 750 mg dose level, and one DLT (toxic epidermal necrolysis) at the 1000 mg dose level. The study was closed due to slow accrual. Median neurological PFS was 2.3months (range 1.6–4.0 months); median OS was 3.5months (range 1.6–5.1months). Though there were no radiologically documented remissions of LM disease, four patients had improvement in neurological symptoms. One patient cleared their CSF of NSCLC cells, while 2 others had decrease in malignant cells in CSF. Conclusion: Although the MTD was not defined due to slow accrual, this study provides important information about the tolerability and CSF penetration of high-dose gefitinib as a therapeutic option for modest palliation for NSCLC patients with LM and a known EGFR mutation.

This is the second feature appearing in our “On the Lighter Side of Science” column. Dr. Joanne Morse is the highlighted writer once again and will talk about different aspects of science from a no...

Advances in membrane technology have yielded ultra low pressure reverse osmosis (ULPRO) systems as a potential water softening process. In order to establish the relative economic performance of such systems, they are compared directly with a number of alternative softening techniques through two case studies based on groundwater sites. Results suggest that although RO systems may not be the most cost effective for unblended peak load operation, they are likely to out perform alternative techniques for base load operation, and for base and peak load operations where high blending ratios are possible.

The importance of integrating environmental considerations into economic analyses has been widely recognized. Indeed, the UK Government has made a commitment to evaluating environmental costs and benefits in investment appraisal techniques in both UK Sustainable Development Strategy and the duties of the Environment Agency. However, an evaluation framework is required to provide comprehensive and consistent environmental benefit assessments. In the aquatic environment, techniques based on cost benefit analysis and environmental economics have been developed, but these may not incorporate the full range of factors which determine anthropogenic use. This study considers the application of a broadly-based marketing approach, by translating key marketing concepts to an aquatic environment context, and incorporating assessment techniques from both the physical and management sciences. An assessment approach emerges which includes fundamental demand and supply side considerations in environmental valuation and investment appraisal. The further development and application of this approach offers the prospect of targeting investment on the aquatic environment more effectively.

Two methodologies for evaluating environmental benefits arising from investment in the aquatic environment have been applied to a series of nine case studies. One methodology was developed by the Foundation for Water Research (FWR), the other is based on a marketing approach translated to the aquatic environment. Results suggest broader consideration of demand and supply-side factors, offered by the marketing-based approach, enables a clearer understanding of anthropogenic use of aquatic resources to be developed. Consequently, estimated environmental benefits are more likely to reflect actual levels of resource use and the nature of a given site, and provide a strategic perspective on investment appraisal. In addition, a rapid assessment technique emerges which facilitates an efficient methodology focusing on essential assessment criteria.

This study examines the potential economic and environmental advantages of materials recovery with particular reference to the putrescible fraction of household waste. By weight, a third or more of domestic refuse comprises biowaste. With regard to haulage alone, clear financial benefits could be realised by diverting it to an appropriate waste treatment facility which is proximal to source. A cost-benefit model is presented to compare anaerobic co-digestion at sewage treatment works with incineration and composting, as alternatives to landfill. Composting is considered to be a biowaste recycling process, incineration a disposal option with potential for electricity generation, and anaerobic digestion combines biowaste recycling with electricity generation. Compartmentalisation of waste enables it to be treated by the best appropriate technology, and has the potential to reduce total cost. Taken in isolation it could account for recovery of a third or more of the municipal wastestream, and integrated with...

The mechanical properties of SiC films grown via C60 precursors were determined using atomic force microscopy (AFM). Conventional silicon nitride and diamond-tipped steel AFM cantilevers were employed to determine the film hardness, friction coefficient, and elastic modulus. The hardness is found to be 26 GPa by nanoindentation of the film with a Berkovich diamond tip. The friction coefficient for the silicon nitride tip on the SiC film is about one half to one third that for silicon nitride sliding on a silicon substrate. By combining nanoindentation and AFM measurements an elastic modulus of ~300 GPa is estimated for these SiC films.

Contemporary theories emphasize the involvement of the endogenous opioid system in assigning hedonic values to rewards. Although earlier research supports this view, recent findings suggest that opioids play a larger and more complex role in reward processes than these theories suggest. For example, opioid activity in the basolateral amygdala is required for encoding incentive learning, a process by which the value of goal-directed actions is updated. Outside the amygdala, opioid receptors in the ventral striatum have been found to promote choice between different courses of action. Specifically, μ opioid receptors in the nucleus accumbens core and δ opioid receptors in the nucleus accumbens shell have been reported to mediate distinct aspects of incentive motivation; the core regulating the effect of experienced reward and the shell of predicted reward on choice. In both cases, the involvement of opioid receptors was restricted to the time of choice, although changes in their expression pattern could be observed prior to that point. This time-restricted involvement of opioid receptor-related processes is consistent with the view that opioids in the nucleus accumbens are central components of the limbic-motor interface, integrating reward-related information with instrumental learning to guide decision-making, particularly the selection and execution of goal-directed actions.This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

There is increasing pressure for the full environmental consequences of investment decisions to be included in project appraisal procedures. Environmental economic valuation techniques offer the potential for monetary values to be systematically estimated for such consequences and thus allow their inclusion in project analysis. A review of these techniques has been undertaken, and by way of testing their practical application a desk-top valuation of Rutland Water, UK, has been carried out. The results indicate that the total annual value of the reservoir is between £123 million and £215 million. However, of this total a minimum of 64% is attributable to functions additional to its primary purpose as a source of potable supply. The magnitude of these additional values indicates that confidence in them can only be achieved by further investigation into their theoretical and methodological basis.

The environmental impact of small-scale sewage-treatment works has been evaluated using the technique of ‘life-cycle analysis’. Three sewage-treatment works with different process options were analysed to identify and quantify material use, energy use and environmental releases during construction, operation and demolition. This enabled (i) a comparison to be made between process options, and (ii) the identification of opportunities for the improvement of environmental performance. Subject to satisfactory sewage treatment and sludge disposal, the technique identified additional impacts of importance, which have implications for energy management, works design, supplier management and general environmental policy. Life-cycle analysis provides a useful insight into environmental impact and has potential for wider application within the water industry.

This study documents the development of a link between a geographical information system (GIS) and a non-point source pollution model. The GIS ARC/INFO was linked to the agricultural non-point source pollution model and ORACLE data sources. Application of the system is demonstrated using the Bedford-Ouse catchment as a suitable case study. Water quality impacts are predicted from source data describing topography, soils, land use and river network. The model results were in agreement with observed nitrate concentrations at the catchment outlet, and more appropriate data sources are considered to be the main priority for improving model predictive ability. Management scenarios were established to assess the impact of changing agricultural management practices on predicted water quality. The approach has significant potential for the management of agricultural pollution in the UK.

This paper explores the proposal that some nine and ten-year old children with serious writing problems do not make progress because much of their instruction is centered around their weaknesses rather than around their strengths. Many children who cannot read or write well by the time they are in the fourth grade are able to learn from visual and aural sources in relevant contexts, but their work in school relies mostly on textual sources as they progress through the grades. Images and sounds can provide children with information in cultural, social, and emotional contexts that are readily accessible to them. The lack of access to such resources is especially acute for children from backgrounds that differ from the culture assumed by school but also occurs for some children from mainstream backgrounds who work better in visual and aural than in textual modes. Since some of the functions of written language, like providing information and means of expression, can be served by other symbol systems, it is worth exploring children's use of a variety of symbol systems and relationships between visual symbol systems, aural symbol systems, and text. Recent developments in technology make it possible to create multimedia environments in the computer including images, sounds, text, and tools for manipulating and transforming these symbol systems. As children gather and study pictures and sounds on a relevant topic, they may be able to use these images and sounds as springboards for writing and extending beyond familiar contexts. But, there is little research to determine whether and how children use such multimedia tools to build bridges between their lives and the world of text, which they must inhabit to be successful in school.

A novel fibre-optic sensor has been designed to function as a real-time plasma diagnostic tool. Plasma composition and discharge power have been monitored by recording the chromaticity of the glow discharge. The chromatic sensor operates in a manner analogous to the human eye and consists of three photodiodes with overlapping spectral responses. When used in conjunction, the three photodiodes are capable of measuring the hue and saturation of a plasma emission spectrum, in addition to the intensity measured by traditional photodiode sensors. Hue and saturation can be mapped onto a chromatic plane, each point of which corresponds to a set of spectra. Although many spectra can be mapped onto a single point on the chromatic plane, the degree of degeneracy is less than that of intensity sensors where spectra map into points restricted to a line. Chromatic sensing is shown to retain the cost and sampling rate advantages of intensity sensors whilst demonstrating an ability to detect spectral shifts, more often associated with spectrometry.

The earth provides myriad ecosystem services or 'benefits' that enable and enhance human existence. Humanity, in turn, imposes myriad environmental impacts or 'costs' on the earth. We explore the idea of mapping these 'costs' and 'benefits' using proxy measures. We set the total value of the world's ecosystem services to be equal to the total cost of anthropogenic environmental impacts at fifty trillion dollars (roughly the global GDP in the year 2000). A global representation of ecosystem service value is mapped at 1 km² resolution using Net Primary Productivity (NPP) as a proxy measure of ecosystem service value ('benefit'). A similar global representation of environmental impact is mapped using pavement (i.e., anthropogenically created impervious surface area or ISA) as a proxy measure of 'cost'. Subtracting the 50 trillion mapped onto ISA from the 50 trillion mapped onto NPP produces a 1 km² resolution map of those areas where: (1) human imposed costs exceed naturally supplied benefits, resulting in an ecological deficit, (2) human costs balance with environmental benefits and (3) environmental benefits exceed human costs, resulting in an ecological surplus. Mapping this ecological balance produces a spatially explicit and monetized representation of ecological sustainability that can be aggregated to national, sub-national, and regional levels. Aggregations of this map at the national level are compared with other national measures of biophysical sustainability such as the Global Footprint Network's 'Eco-Deficit'. An additional benefit of this approach is that the national values derived from this difference map suggest a starting point for discussions of the dollar values and costs of both under and over consumption of ecosystem services on the part of the nations of the world. Refereed/Peer-reviewed

Disseminated sclerosis is currently regarded as a CNS autoimmune disease. One of the mechanisms behind this pathology is antibody (AB) formation. In this context, recent data on AB with proteolytic activity are of importance because they participate in selective proteolysis of myelin proteins in patients with disseminated sclerosis. This paper focuses on AB-proteases associated with disseminated sclerosis and site-specificity of antibody-mediated proteolysis of myelin basic protein. Protocol of serodiagnostic algorithm to be used in clinical practice is described.

In 2009 the global coal market witnessed one of the most dramatic realignments it has ever seen – China, long a net exporter of coal, suddenly imported a record-smashing 126 Mt tons (103 Mt net). This inversion of China’s role in global coal markets meant that Chinese imports accounted for nearly 15% of all globally traded coal, and China became the focal point of global demand as traditional import markets like Europe and Japan stagnated in the wake of the financial crisis. The middle kingdom's appetite for imported coal seems insatiable, and the “China Factor” appears to have ushered in a new paradigm for the global coal market.But China doesn’t ”need” the coal. The world's largest coal producer cranked out 2.96 Bt of production in 2009, backed up by 114.5 Bt of reserves. While the world’s other fastest growing importer, India, is plagued by a growing gap between coal supply and power demand that it is unable to fill domestically, this is not the case in China. The spike in Chinese demand for imported coal is therefore a more complex (and less easily predictable) phenomenon that requires careful examination if the world is to understand what impact China might have on global energy markets in the coming decade.In this paper Richard Morse and Gang He devise a model that explains Chinese coal import patterns and that can allow the coal market to understand, and to some degree predict, China’s coal import behavior. They argue that the unique structure of the Chinese coal market creates a series of key arbitrage relationships between Chinese domestic coal markets and international coal markets that determine Chinese import patterns.The implications of this argument are significant for the development of the global coal trade in the coming decade. The arbitrage relationships that Morse and He describe directly link the domestic price of coal in China to the global price of coal. Developments in China‘s domestic coal market will be a dominant factor determining global coal prices and trade flows (and by implication power prices in many regions). This makes understanding the domestic Chinese coal market, which operates according to a unique economic and political logic, crucial for any participant in the global markets.

China's coal market is now in the midst of a radical restructuring that has the potential to change how coal is produced, traded and consumed both in China and the rest of the world. The restructuring aims to integrate the coal and power sectors at giant "coal-power bases" that combined would churn out more coal annually than all the coal produced in the entire United States. Coal-power integration is now a focal point of the Chinese government's energy policy, driven by the dramatic "coal-power conflict." Coal prices are market-based, but power prices are tightly controlled by the government. This has caused massive losses for Chinese power generators in 2008 and 2010 and triggered government intervention in the coal market with attempts to cap the price of coal. The pervasive conflict between coal and power is now driving the Chinese government to remake these markets.Coal-power base policy aims to establish upwards of 14 major coal-power bases, each producing over 100 mt of coal with consuming industries on-site. The plan envisions that roughly half of China's coal production would be produced at a handful major coal-power base sites that are controlled by key state-owned enterprises (SOEs) and the central government. PESD's new research analyzes China's coal-power base reforms and how they will impact Chinese and global coal markets. Several key findings are:First, the implementation of coal-power bases would enhance central government's control over the coal sector and over coal prices. The government could control coal pricing in a large share of the market and mitigate power sector losses by mandating lower coal transaction prices within integrated SOEs. Using this kind of internal transfer pricing at below market prices for up to half of China's coal would represent a meaningful shift in how coal is priced in China. If a large share of China's coal were transacted in this manner, it might create an unofficial two-tiered pricing structure in the coal market.Second, coal-power base policy would bring about modernization and mechanization of a larger share of China's coal production, in theory bringing larger economies of scale to the sector. While up-front capital investment per ton produced will certainly increase, the marginal cost of coal production should decrease, all other things equal. Third, the massive rebalancing of China's coal market implied by coal-power bases is poised to have important impacts on the globally traded coal market. Since 2009, China's import behavior has become a dominant factor determining the price of globally traded coal. In simple terms, when Chinese domestic prices are higher than global prices, the country imports. The development of coal-power bases could radically alter coal price formation in China and directly impact China's appetite for imports, and therefore has the potential to alter coal price formation globally.

The Clean Development Mechanism (CDM) is the leading international carbon market and a driving force for sustainable development globally. But the eruption of controversy over offsets from Chinese wind power has exposed cracks at the core of how carbon credits are verified in developing economies. It has become almost impossible to determine whether offsets from Chinese wind are "additional" and that they in fact represent "real" reductions beyond business as usual. Unless this problem can be resolved, it threatens to spread beyond wind in China and could threaten the ability of carbon markets to deliver the mitigation demanded by international climate policy.In 2009 the CDM Executive Board (EB) shocked the carbon market by forcing an unprecedented review of whether multiple Chinese wind projects satisfied UNFCCC additionality requirements. CDM investors reeled as the safest CDM bet became the riskiest; the Chinese government publicly criticized the UN's oversight of carbon markets; and the CDM EB prepared itself for an unprecedented fight over how carbon offsets could be verified in the world's largest CDM market.When the EB observed decreases over time in power tariffs granted by China's National Development and Reform Commission (NDRC) to wind projects, it became concerned that China might be manipulating power tariffs in order to guarantee additionality and subsidize its domestic wind development with international finance. If the Chinese government were controlling additionality, then the CDM's ability to validate carbon offsets would be dealt a near‐lethal blow because the problems posed by Chinese wind extend to nearly all power sector projects in almost every developing country. If offsets cannot be credibly verified, then the integrity of emissions caps set by the Kyoto Protocol is directly threatened.The Chinese wind controversy therefore has direct implications for the design and negotiation of any successor to the Kyoto Protocol. Despite largely failed negotiations in Copenhagen, the design of reliable, efficient carbon markets remains the world's most serious prospect for international cooperation. The developed world has committed USD 30 billion in climate aid by 2012, but the majority of these funds will likely have to be private capital delivered through markets. In order for carbon markets to avoid controversy and function effectively, the lessons from the Chinese wind controversy must be used to implement key reforms.This report examines the application of additionality in the Chinese wind power market and draws implications for the design of effective global carbon offset policy. It demonstrates the causes of the wind power controversy, highlights underlying structural flaws in how additionality is applied in China, and charts a reform path that can strengthen the credibility of global carbon markets.

The mediation of lesion-induced sprouting in the nervous system is a complex interaction of local membrane factors and circulating hormones. This series of studies examines the reactivity of the sprouting response of both male and female subjects under different hormonal conditions. Young adult male and female Sprague-Dawley rats which were gonadectomized (GDX) and adrenalectomized (ADX) underwent a unilateral entorhinal cortex lesion, which partially denervates the molecular layer of the ipsilateral hippocampal dentate gyrus. At the time of the lesion, each animal received hormonal therapy. Fifteen days post-ERC-ab-lation the brains were analyzed for changes in reactive fiber outgrowth in the hippocampal commissural/associational afferents. Fiber outgrowth in females in the “asteroidal” ( GDX ADX ) condition was unaffected. Asteroidal males demonstrated a decreased response. Gonadal steroid replacement, estrogen or testosterone, enhanced outgrowth in both asteroidal males and females. Glucocorticoid replacement suppressed outgrowth in both asteroidal males and females. Gonadal steroids clearly have neurotrophic activity which is interactive with glucocorticoid activity. Glucocorticoids under the GDX ADX conditions in vivo have a negative impact on fiber outgrowth in both sexes. The effect of glucocorticoids is most dramatic when compared to the outgrowth of asteroidal animals without additional hormonal supplementation.