To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Addiction is characterized by excessive desire for a particular substance or behavioral incentive at the expense of other life rewards. Addictive desire can develop even in absence of any associated increase in pleasure, and also in absence of withdrawal. Here we review evidence that the brain mechanisms underlying desire or ‘wanting’ can operate independently from those mediating pleasure, or "liking." That is, "wanting" and "liking" are mediated by two anatomically and neurochemically distinct brain mechanisms that normally interact together to influence motivation, but can become dissociated in the transition to addiction. Pleasure "liking" is the hedonic impact of a pleasant stimulus and is causally amplified by a brain system of several functionally interactive but anatomically distributed locations referred to as "hedonic hotspots." These hedonic hotspots are localized subregions within larger brain structures, and are relatively sensitive to disruption. By contrast, "wanting" or the subconscious desire for reward or reward-related cues is much more robust, and mediated by a larger brain system. "Wanting" can be generated by dopamine enhancements as well as by opioid enhancements in several broadly defined regions throughout mesocorticolimbic circuitry. In susceptible individuals, mesolimbic circuitry can become hyperreactive or sensitized (e.g., through previous drug experience), so that "rewards" and their related cues evoke even greater dopamine release and "wanting." Sensitized "wanting" becomes harder to resist, which can spur on excessive and compulsive pursuit and relapse in addiction. Importantly, this sensitization of brain "wanting" systems need not be accompanied by an enhancement of brain "liking" (i.e., dopamine manipulations do not appear to effect pleasure). In this chapter, we also highlight possible mechanisms for how some drugs or behaviors become the specific focus of excessive but narrow pursuit, usually involving mesolimbic brain interactions with areas such as the amygdala. Further we demonstrate that behavioral addictions such as food addiction and gambling, like drug addiction, are accompanied by sensitization of mesolimbic brain "wanting" systems in the transition to addiction.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Recent infection testing algorithms (RITA) for HIV combine serological assays with epidemiological data to determine likely recent infections, indicators of ongoing transmission. In 2016, we integrated RITA into national HIV surveillance in Ireland to better inform HIV prevention interventions. We determined the avidity index (AI) of new HIV diagnoses and linked the results with data captured in the national infectious disease reporting system. RITA classified a diagnosis as recent based on an AI < 1.5, unless epidemiological criteria (CD4 count <200 cells/mm3; viral load <400 copies/ml; the presence of AIDS-defining illness; prior antiretroviral therapy use) indicated a potential false-recent result. Of 508 diagnoses in 2016, we linked 448 (88.1%) to an avidity test result. RITA classified 12.5% of diagnoses as recent, with the highest proportion (26.3%) amongst people who inject drugs. On multivariable logistic regression recent infection was more likely with a concurrent sexually transmitted infection (aOR 2.59; 95% CI 1.04–6.45). Data were incomplete for at least one RITA criterion in 48% of cases. The study demonstrated the feasibility of integrating RITA into routine surveillance and showed some ongoing HIV transmission. To improve the interpretation of RITA, further efforts are required to improve completeness of the required epidemiological data.
The infection status of angiostrongylosis in Jamaica was assessed in wild rats and molluscs in the 5 years following the major outbreak of eosinophilic meningitis (EM) in 2000. Parasitological analyses of 297 Rattus rattus and 140 Rattus norvegicus, and 777 terrestrial molluscs from all 14 Parishes on the island revealed Angiostrongylus cantonensis in 32·0% of the rats and in 12·5% of the molluscs. Multivariate analyses confirmed that A. cantonensis occurred significantly more frequently in R. rattus (Odds Ratio [OR] = 1·76), while mean infection intensity in R. rattus was also significantly higher (16·8) than R. norvegicus (11·3) (Mann–Whitney U-test: P = 0·01). Third-stage larvae of A. cantonensis were detected in 29% of 86 Pleurodonte spp.; in 20% of five Poteria spp.; in 18·7% of 369 Thelidomus asper; in 11% of 18 Sagda spp.; and in 6% of 24 veronicellid slugs. Most rodent infections occurred in Northeastern Jamaica (OR = 11·66), a region where infected molluscs were also abundant. Given the prevalence of A. cantonensis infection in rats has significantly increased since the 2000 outbreak, and that a survey of human infections revealed at least ten autochthonous cases in the last 15 years, angiostrongylosis persists as an important zoonosis in Jamaica.
We examine the roles of actuaries in UK life offices, along with trends, challenges to and opportunities for actuaries. We carry out an analysis of senior roles in life offices, a questionnaire survey and interviews with relevant senior personnel. We find that actuaries occupy many important roles in life offices and are regarded as having good industry knowledge and technical skills, especially in financial modelling. There are fewer executive directors and more non-executive directors of life offices who are actuaries compared with the position in 1990. A higher proportion of reserved roles is outsourced to consultants than was the case in 1990. Only a small number of Actuarial Function Holders are directors. Actuaries are more siloed than was the case in the past, although actuaries are well represented in the finance and risk functions of many offices. Although actuarial work in connection with the preparation for Solvency II will decline, there will be important ongoing requirements for actuaries following Solvency II implementation. We also see opportunities for actuaries in four areas: in risk management, in financial analysis and management based on Solvency II and international financial reporting standards, in connection with “big data”, and in product development and the customer proposition. There are implications for the examination syllabus, continuing professional development and research.
Various environmental factors have been associated with the timing of eruption of primary dentition, but the evidence to date comes from small studies with limited information on potential risk factors. We aimed to investigate associations between tooth emergence patterns and pre-conception, pregnancy and postnatal influences. Dentition patterns were recorded at ages 1 and 2 years in 2915 children born to women in the Southampton Women’s Survey from whom information had been collected on maternal factors before conception and during pregnancy. In mutually adjusted regression models we found that: children were more dentally advanced at ages 1 and 2 years if their mothers had smoked during pregnancy or they were longer at birth; mothers of children whose dental development was advanced at age 2 years tended to have poorer socioeconomic circumstances, and to have reported a slower walking speed pre-pregnancy; and children of mothers of Asian ethnicity had later tooth development than those of white mothers. The findings add to the evidence of environmental impacts on the timing of the eruption of primary dentition in indicating that maternal smoking during pregnancy, socio-economic status and physical activity (assessed by reported walking speed) may influence the child’s primary dentition. Early life factors, including size at birth are also associated with dentition patterns, as is maternal ethnicity.
Novel and more conventional boron carbides were combined with n-type silicon to make heterojunction diodes, with neutron capture signal at zero applied bias. The boron carbides were based on the cross linking of closo-1,2-dicarbadodecaborane (ortho-carborane; 1,2-B10C2H12), and cross linking based on the combination of closo-1,2-dicarbadodecaborane (ortho-carborane; 1,2- B10C2H12) and pyridine. In the latter devices, pyridine concentration was varied; samples with a closo-1,2-dicarbadodecaborane (ortho-carborane; 1,2- B10C2H12) to pyridine ratio of 1:1 (BC:Py1) and 1:3 (BC:Py3). The result is a nonvolatile robust p-type semiconductor of boron carbide (B10C2Hx):(C5NHx)y. The I(V) curves for the resulting heterojunction diodes exhibit strong rectification where the normalized reverse bias leakage currents are largely unperturbed with increasing pyridine inclusion. The devices are largely gamma insensitive and yet neutron voltaic properties of these boron carbides is demonstrated. The neutron capture generated pulses from these heterojunction diodes were obtained at zero bias voltage although without the characteristic signatures of complete charge collection from boron neutron capture generated electron-hole pair production. These results, nonetheless, suggest that modifications to boron carbide may result in better neutron voltaic materials with linking groups chosen from family of aromatic compounds that stretch between borazine (B3N3H6) and benzene that point the way to a whole family of future studies that may ultimately lead to boron carbides better suited to low power and low flux neutron detection.
The 2013 Infection Prevention and Control (IP&C) Guideline for Cystic Fibrosis (CF) was commissioned by the CF Foundation as an update of the 2003 Infection Control Guideline for CF. During the past decade, new knowledge and new challenges provided the following rationale to develop updated IP&C strategies for this unique population:
1. The need to integrate relevant recommendations from evidence-based guidelines published since 2003 into IP&C practices for CF. These included guidelines from the Centers for Disease Control and Prevention (CDC)/Healthcare Infection Control Practices Advisory Committee (HICPAC), the World Health Organization (WHO), and key professional societies, including the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). During the past decade, new evidence has led to a renewed emphasis on source containment of potential pathogens and the role played by the contaminated healthcare environment in the transmission of infectious agents. Furthermore, an increased understanding of the importance of the application of implementation science, monitoring adherence, and feedback principles has been shown to increase the effectiveness of IP&C guideline recommendations.
2. Experience with emerging pathogens in the non-CF population has expanded our understanding of droplet transmission of respiratory pathogens and can inform IP&C strategies for CF. These pathogens include severe acute respiratory syndrome coronavirus and the 2009 influenza A H1N1. Lessons learned about preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative pathogens in non-CF patient populations also can inform IP&C strategies for CF.
The purpose of this study was to describe the longitudinal trajectories and bidirectional relationships of the physical-social and emotional functioning (EF) dimensions of positive aging and to identify their baseline characteristics.
Women age 65 and older who enrolled in one or more Women's Health Initiative clinical trials (WHI CTs) and who had positive aging indicators measured at baseline and years 1, 3, 6, and 9 were included in these analyses (N = 2281). Analytic strategies included latent class growth modeling to identify longitudinal trajectories and multinomial logistic regression to examine the effects of baseline predictors on these trajectories.
A five-trajectory model was chosen to best represent the data. For Physical-Social Functioning (PSF), trajectory groups included Low Maintainer (8.3%), Mid-Low Improver (10.4%), Medium Decliner (10.7%), Mid-High Maintainer (31.2%), and High Maintainer (39.4%); for EF, trajectories included Low Maintainer (3%), Mid-Low Improver (9%), Medium Decliner (7.7%), Mid-High Maintainer (22.8%), and High Maintainer (57.5%). Cross-classification of the groups of trajectories demonstrated that the impact of a high and stable EF on PSF might be greater than the reverse. Low depression symptoms, low pain, and high social support were the most consistent predictors of high EF trajectories.
Aging women are heterogeneous in terms of positive aging indicators for up to 9 years of follow-up. Interventions aimed at promoting sustainable EF might have diffused effects on other domains of healthy aging.
We studied the effect of a cross-conjugated bridging group (χC) on charge-transfer in a push-pull chromophore system. The hyperpolarizability of such molecules was found to be comparable to that of a fully π-conjugated molecule (πC) with the same donor and acceptor. The cross-conjugated moiety was then applied as a pendant to a fully π-conjugated chromophore containing a tricyanopyrroline acceptor (TCP). The addition of a χC moiety did not alter the intrinsic hyperpolarizability and provides an avenue for extending and aiding πC systems. The molecules were examined by X-ray diffraction (XRD), hyper-Raleigh scattering (HRS) and UV-visible (UV-vis) spectroscopy. Experimental results were compared with the predictions of density functional theory (DFT). Cross-conjugated molecules have comparable β values, relative to πC molecules, due to reduced spatial overlap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). Thus, the χC architecture could facilitate independent modification of donor and acceptor strengths while minimizing unfavorable effects on electronic transitions and dipole moments.
The use of organic nonlinear optical (ONLO) materials in electro-optic (EO) modulators requires that the active molecular components (chromophores) be acentrically oriented. The fundamental molecular constituents are in a condensed, glassy phase. Molecular orientation in such systems is typically achieved by applying a DC poling field to the glassy material. We are developing efficient coarse-grained classical Monte Carlo (MC) methods to simulate the order of such systems. The most challenging aspects of these simulations are convergence to an experimentally relevant equilibrium ensemble and verification of simulation accuracy. We use a variety of molecular descriptions and a variety of MC methods to achieve proper order in the shortest number of computational cycles possible. Herein, we illustrate a few examples of the types of calculations and compare with experimental results with representative amorphous organic materials, including electro-optic chromophores.
As governments and institutions work to ameliorate the effects of anthropogenic CO2 emissions on global climate, there is an increasing need to understand how land-use and land-cover change is coupled to the carbon cycle, and how land management can be used to mitigate their effects. This book brings an interdisciplinary team of fifty-eight international researchers to share their novel approaches, concepts, theories and knowledge on land use and the carbon cycle. It discusses contemporary theories and approaches combined with state-of-the-art technologies. The central theme is that land use and land management are tightly integrated with the carbon cycle and it is necessary to study these processes as a single natural-human system to improve carbon accounting and mitigate climate change. The book is an invaluable resource for advanced students, researchers, land-use planners and policy makers in natural resources, geography, forestry, agricultural science, ecology, atmospheric science and environmental economics.