bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Wartime Violence on Young Bosnians’ Postwar Behaviors
Authors: McCouch Robert J.
Published: April 2010

Given that there has been very little explicit attention to policy concerns in the research literatures on youth and political violence, this chapter uses a policy lens to focus on existing empirical data in an attempt to understand the relationship between young Bosnians' wartime experiences and their post-conflict behaviors. It also documents some of the socioemotional or psychosocial characteristics whereby the effect of violence exposure was transmitted to these negative outcomes. Important policy implications are evident.
Understanding the Social Security Act
Authors: Dobelstein Andrew
Published: April 2010

America's social welfare commitments, including retirement and disability payments, unemployment insurance, Medicare and Medicaid, the State Child Health Insurance Program, Supplemental Security Income, and Temporary Assistance to Needy Families, face mounting pressures as economic and social challenges escalate. It was originally created in 1935 to mitigate the personal economic hardships of the Great Depression on future cohorts of Americans. Many social welfare policy experts fail to grasp the intricacy and complexity of America's obligations as they are woven together under the authority of the Social Security Act. While frequently examined for their separate distinguishing characteristics, the many programs of the Act are linked to one another so that modification to one program creates the need for change in other programs. An incremental development of America's social welfare commitments through the Social Security Act over the past 75 years has produced a confusing manifestation of social welfare undertakings, often making it difficult to comprehend and/or modify any single program without a comprehensive overview of the policy and program dynamics of America's complete social welfare commitments. The present economic recession highlights the necessity of the Social Security Act on the one hand, but also uncovers 21st century social welfare issues that cry for changes in those programs authorized by the Act. Still, the Social Security Act provides the only coherent policy framework for understanding America's effort to meet her social welfare commitments, and provides guidance for the changes in America's social welfare programs necessary in today's unique social and economic environment.
Title XVI: Supplemental Security Income
Authors: Dobelstein Andrew W.
Published: April 2010

Title XVI of the Social Security Act, Supplemental Security Income (SSI), evolved as a hybrid form of assistance with a mixed pedigree. Daniel Patrick Moynihan sought to convince President Nixon to make all the assistance programs that existed under the original Social Security Act into a single assistance program administered by the Federal government, similar to the insurance programs. The complexity of blending the original assistance programs — Aid for the Aged (AA, Title I), Aid to Families with Dependent Children (AFDC, Title IV), Aid for the Blind (AB, Title X) and Aid for the Disabled (AD, Title XIV) — into a single federally administered assistance program proved too ambitious. Not only were the programs poorly matched, but also the policy objectives of assistance clashed with President Nixon's efforts to reduce the social welfare responsibility of the Federal government. SSI was finally created when Aid to Families with Dependent Children was left to stand alone as a state administered program.
Titles XIX and XXI: Medicaid and the State Child Health Insurance Program
Authors: Dobelstein Andrew W.
Published: April 2010

Both Medicaid and the State Child Health Insurance Program (SCHIP) are medical assistance programs. Federal funds are granted to states to help defray the costs of providing medical services to financially needy children and adults. State financial participation is required like it is in all grants in aid programs. While the Federal government insists that states provide specific services under their programs, states are free to provide more than required services. In most cases, states set conditions for eligibility for these programs. Medicaid is provided to all persons who can not afford their own medical care, and SCHIP is reserved for children; in practice, however, there is considerable overlap in the programs. Different Federal funding for these programs has produced a state-by-state patchwork pattern of health services for the poor.
Title XX: Social Services
Authors: Dobelstein Andrew W.
Published: April 2010

Including social services as part of the foundation of America's social welfare obligation recognized a long-standing tradition that, rather than providing money, economic need could be mitigated by helping individuals become more independent and socially stable, thus achieving financial independence. Yet in spite of years of struggle to achieve a “service strategy”, the exact nature of social services and their application remained unclear. Provision of specific products like day care (“hard services”) and counseling (“soft services”) are provided at the discretion of the states, funded by several block grants.
The Social Security Act for America′s Twenty-First Century
Authors: Dobelstein Andrew W.
Published: April 2010

The story of the Social Security Act documents the growth and development of America's social welfare commitments within the framework of a monumental social, economic and political document. The 75-year debate over the proper social welfare role of the Federal government enters the 21st century with a well-institutionalized policy certificate, but the incremental tinkering with the Act's social programs over the years has left a bewildering array of policies and programs, many unsuited to today's social welfare needs. Unemployment insurance offers a striking example of the need for renovation. Yet the need for overhaul remains a reluctance that, once opened for debate, some of the social welfare advances assured by the Social Security Act may be lost.
Ways of Seeing
Authors: Jacob Pierre , Jeannerod Marc
Published: April 2010

This book is about human vision. It results from the collaboration between a world famous cognitive neuroscientist and an eminent philosopher. In the past forty years, cognitive neuroscience has made many startling discoveries about the human brain and about the human visual system in particular. This book brings many recent empirical findings, from electrophysiological recordings in animals, the neuropsychological examination of human patients, psychophysics, and developmental cognitive psychology, to bear on questions traditionally addressed by philosophers. What is the meaning of the English verb ‘to see’? How does visual perception yield knowledge of the world? How does visual perception relate to thought? What is the role of conscious visual experience in visually guided actions? How does seeing actions relate to seeing objects? In the process the book provides a new assessment of the ‘two visual systems’ hypothesis, according to which the human visual system comprises two anatomical pathways with separable visual functions.
The representational theory of the visual mind
Authors: JACOB PIERRE , JEANNEROD MARC
Published: April 2010

This chapter sketches and argues for a view called the ‘representational theory of the visual mind’ (RTVM). RTVM is not so much a scientific theory that leads to testable predictions, as a picture or a framework. According to this theory, the mind is at bottom a representational device: in Dretske's terms, ‘all mental facts are representational facts’. In this view, mental processes consist of the formation and the transformation of mental representations. Section 2 contrasts RTVM with two alternatives: ‘sense-datum theory’ and ‘disjunctivism’. Section 3 presents reasons for thinking that visual percepts have non-conceptual content. Section 4 sketches the basis of an approach labelled as ‘cognitive dynamics’. Section 5 considers three implications of RTVM for the control of visually guided actions. It argues that RTVM has the resources to clarify the puzzle of visually guided actions. It examines the nature of actions and argues that actions involve mental representations.
Multiple pathways in the primate visual system
Authors: JACOB PIERRE , JEANNEROD MARC
Published: April 2010

This chapter reviews the progressive build-up by anatomists and physiologists of the concept of multiple visual systems with specialized functions. In particular, it examines the grounds for distinguishing a visual subsystem dedicated to localizing a stimulus (the ‘where’ system) from a visual subsystem dedicated to its identification (the ‘what’ system). It contrasts the responses of single neurons located, respectively, in the anterior intraparietal area (AIP) and in the inferotemporal area (TE) of the brain of macaque monkeys. The former responds to the geometrical properties of objects relevant in the context of grasping tasks. The latter responds to more complex visual properties of the same objects.
Seeing humans act
Authors: JACOB PIERRE , JEANNEROD MARC
Published: April 2010

This chapter examines how the human visual system responds to human actions. Section 1 starts with the examination of the human ‘praxic’ system, i.e. a high-level visual pragmatic processing of artifacts as tools. Section 2 examines what seems to be the primary level of the visual analysis of human action, namely the perception of biological motion. Sections 3 and 4 ascend from the primary level to higher levels of the visual analysis of human actions, and argue that the human visual system has two complementary specialized neural circuits for processing human actions. The chapter distinguishes between non-social motor intentions and social intentions to reflect the difference between an intention to grasp an object and an intention to affect a conspecific's behaviour, which, in the human case, may involve the intention to cause a new mental state or representation, e.g. fear or a belief, in a conspecific on the basis of visual cues.
Epilogue: the two visual systems revisited
Authors: JACOB PIERRE , JEANNEROD MARC
Published: April 2010

This chapter discusses how the dualist model of human visual processing presented in the book departs from Milner and Goodale's (1995) dualist model. It first argues that the concept of action involved in their notion of ‘vision-for-action’ is overly narrow. In the process, it reflects on the complexities of the notion of a perceptual object. The chapter then argues that Milner and Goodale's model underestimates the role of the parietal lobes, not only in the organization of high-level pragmatic visual processing (i.e. for action) but also, for the visual perception of spatial relationships.
Photopigment Polymorphism in Prosimians and the Origins of Primate Trichromacy
Authors: Jacobs Gerald H. , Deegan II Jess F.
Published: April 2010

This chapter describes a study of photopigment polymorphism in prosimians. A noninvasive electrophysiological technique, electroretinogram (ERG) flicker photometry was used to measure spectral sensitivity in three adult (one male, two female) black and white ruffed lemurs (Varecia variegata variegata). The pigment polymorphism observed in black and white ruffed lemurs predicts variations in colour vision. Two of the animals could be dichromatic, each with distinctly different colour vision characteristics, while the third (a female) has the photopigment basis for trichromacy. With the recent evidence that prosimians have cone opsin gene and photopigment polymorphisms, it seems clear that the idea that only anthropoid primates can be trichromatic was mistaken. At the same time, it is equally clear that the number of prosimians potentially enjoying trichromacy may be limited.
The Arrangement of Land M Cones in Human and a Primate Retina
Authors: Bowmaker J. K. , Parry J. W. L. , Mollon J. D.
Published: April 2010

The relative numerosities and spatial arrangement of long-wave (L) and middle-wave (M) cones in the human and primate retina have long been debated. This topographical organization of cones is fundamental to the understanding of visual sensitivity and colour vision. This chapter examines the numerosity of L and M cones in the human fovea. It also examines cones at the ora serrata and analyzes the foveal array of a single female marmoset. The data suggests that the ratio of L:M cones in the foveal region in humans varies between individuals from close to unity to at least as high a 5L:M. However, the average for the population is 2:1. In the case of the female marmoset, the two types of long-wave cone were in the ratio 0.7:1. The functional significance of individual variation in the ratio of L and M cones in humans is discussed.
Comparison of Human and Monkey Pigment Gene Promoters to Evaluate DNA Sequences Proposed to Govern L:M Cone Ratio
Authors: McMahon C. , Neitz J. , Neitz M.
Published: April 2010

This chapter examines the genetic mechanisms responsible for the difference in long-wave (L) and middle-wave (M) cone ratio between monkeys and humans. It is possible that sequences of the L and M gene promoter regions influence the L versus M cone decision-making process during development. The similarity between the L and M promoters in Old World monkeys may be related to the nearly equal numbers of L and M cones in these animals, and that some of the additional differences between the human L and M promoters may play a role in producing the difference in L and M cone numbers in human retinas. It is also possible that other differences between L and M genes, for example differences within the introns, may play a role in determining the L:M ratio.
The Neural Circuit Providing Input to Midget Ganglion Cells
Authors: Marshak David W
Published: April 2010

This chapter proposes a neural circuit providing input to a central midget ganglion cell. The narrow field of amacrine cells are unselective in their contacts with bipolar cells, but because their dendritic arbors are small, their responses tend to be biased toward L or M cones, the same type that provides input to most of the nearby midget bipolar cells. The narrow field amacrine cells make inhibitory synapses onto wide field amacrine cells. The wide field amacrine cells inhibit the midget ganglion cells and midget bipolar cells, and they provide the classical, spatially antagonistic surround, as originally proposed by Dowling and Boycott (1996). Because the wide field amacrine cells have much larger dendritic trees, their input reflects the key ratio of L and M cones to the entire region of the retina.
Chromatic Assimilation: Evidence for a Neural Mechanism
Authors: Shevell Steven K. , Cao Dingcai
Published: April 2010

Chromatic induction refers to the shift in colour appearance caused by nearby light. Most research on chromatic induction has focused on colour contrast, which is a shift in appearance away from the colour of the nearby light. Most studies of chromatic assimilation suggest that neural factors contribute to it. The nature of neural mechanisms, however, is often vague or untested. This chapter has two aims. First, a new stimulus is introduced to minimize the influence of prereceptoral factors. Most previous studies of assimilation used contextual light covering half or more of the whole stimulus area. Here, light is induced in various conditions that covers just 9% to 37% of the whole area. Measurements show that chromatic assimilation from this contextual light cannot be explained by prereceptoral factors. Second, the proportion of the whole area covered by inducing light was varied systematically to test for neural summation over the stimulus area. The measurements are generally consistent with neural summation.
Contribution of Achromatic and Chromatic Contrast Signals to Fechner–Benham Subjective Colours
Authors: Le Rohellec J. , Brettel H. , Viénot F.
Published: April 2010

This chapter describes an experiment aimed at examining the respective contribution of achromatic contrast and isoluminant chromatic contrasts for generating subjective colours. It compares the efficiency of cone contrasts that are manipulated in an additive mode or in an antagonistic mode to differentiate subjective colours produced by different spatio-temporal stimuli. The results demonstrate the prevalence of the achromatic contrast to elicit Benham subjective colours. It seems that isoluminant chromatic contrast needs to be boosted to a very high value to produce subjective colours. The findings confirm that S-cone signals alone are inefficient to generate Benham colours.
Convergence as a Function of Chromatic Contrast: A Possible Contributor to Depth Perception?
Authors: Paramei Galina V. , Jaschinski Wolfgang
Published: April 2010

This chapter addresses the question of whether vergence — an oculomotor component of binocular vision — is related to the variation of chromatic information in stimuli, thereby contributing to binocular ‘colour-and-depth’ perception. In particular, the chapter examined whether a near-vergence response elicited by a fusion stimulus would change when stimulus chromatic contrast is varied. The results show that chromatic contrast yields information for a distance cue in dichoptically presented stimuli, as indicated by a systematic increase of the vergence error with reducing contrast. Similarly, reducing luminae contrast results in increasing vergence error.
Red–Green Colour Deficiency and Colour Constancy Under Orthogonal-Daylight Changes
Authors: Amano Kinjiro , Foster David H. , Nascimento Sergio M. C.
Published: April 2010

This chapter presents a computational model of the performance of colour-normal, pronatopic, and deuteranopic observers using information available from long-, medium-, and short-wavelength-sensitive cones. Large anisotropies found with the sample of protan and deutan observers were not reproduced by the corresponding dichromatic models, confirming that information about deviations in spatial cone-excitation ratios in the remaining medium-to-long-wavelength-sensitive cone class was not used effectively.
Schopenhauer’s “Parts of Daylight” In The Light of Modern Colorimetry
Authors: Koenderink Jan J.
Published: April 2010

This chapter argues that although Arthur Schopenhauer's hopes of arriving at a principled basis of colour harmony appears futile, the concept of colours as ‘parts of daylight’ is a valuable one. It shows that the tripartition is very natural, namely the unique solution to the problem of inscribing a ‘best fitting crate’ (a parallelepiped) into the colour solid that exhausts the greatest fraction of its volume.
Some Properties of the Physiological Colour System
Authors: Von Campenhausen C. , Schramme J.
Published: April 2010

The Physiological Colour System (PCS) is an approach towards a uniform colour system. The PCS is based on cone excitations as calculated by the Naka–Rushton relation. This chapter shows that the PCS has a certain degree of uniformity as demonstrated by computed wavelength discrimination curves and MacAdam ellipses.
Extreme Anomalous Trichromatism
Authors: Birch Jennifer
Published: April 2010

Progress in the molecular genetics of colour vision deficiency relies on matching phenotype with genotype. Thus, it is essential that accurate diagnosis of the type of red-green colour deficiency is obtained and that unusual phenotypes, such as extreme anomalous trichromatism, are identified. Accurate diagnosis is obtained by careful determination of the limits of the red-green matching range on a spectral anomaloscope. This chapter shows that extreme anomalous trichromats make matches with a significant excess of both red and green light, but are unable to match all red-green mixture ratios.
Models of nucleotide substitution
Authors: YANG ZIHENG
Published: April 2010

This chapter discusses models of nucleotide substitution and calculation of the distance between a pair of sequences. It introduces the theory of Markov chains and the maximum likelihood method, which are used extensively later in the book. Exercises are provided at the end of the chapter.
Comparison of methods and tests on trees
Authors: YANG ZIHENG
Published: April 2010

This chapter discusses two problems: the evaluation of statistical properties of tree reconstruction methods and tests of the significance of estimated phylogenies. Section 6.1 discusses criteria for assessing the statistical properties of tree reconstruction methods. A summary of simulation studies conducted to evaluate different methods is provided, as well as some recommendations concerning the use of those methods in practical data analysis. Sections 6.2 and 6.3 deal with the likelihood versus parsimony debate from the likelihood and parsimony perspectives, respectively. Section 6.4 provides an overview of methods for assessing the reliability of estimated phylogenies.
Molecular clock and estimation of species divergence times
Authors: YANG ZIHENG
Published: April 2010

This chapter focuses on statistical methods for testing the clock hypothesis, and on likelihood and Bayesian methods for dating species divergence events under global and local clock models. In such an analysis, fossils are used to calibrate the clock, that is, to translate sequence distances into absolute geological times and substitution rates. A similar situation concerns viral genes, which evolve so fast that changes are observed over the years. Then one can use the dates at which the sequences are determined to calibrate the clock and to estimate divergence times, using essentially the same techniques as discussed here.
Introducing Evolutionary Thinking For Medicine
Authors: Stearns Stephen C. , Nesse Randolph M. , Haig David
Published: April 2010

This chapter introduces the book, motivates it with examples of cases in which evolutionary approaches provide useful insights, and provides a brief sketch of evolutionary biology that describes key concepts and misconceptions. It argues that doctors need to know this about evolution: how natural selection works; why trade-offs are ubiquitous; how to distinguish and apply proximate and ultimate explanations; how to distinguish natural selection, drift, and inherited constraints as explanations; why group selection is weak and rarely an explanation; why aging is a by-product of selection for reproductive success earlier in life; why each human differs genetically in reacting to drugs and diseases; how pathogens rapidly evolve antibiotic resistance, and how that can be managed; how pathogen virulence evolves in response to human interventions; how evolutionary conflicts help to explain reproductive problems; and how selection operates in everyday life.
Global spatial patterns of infectious diseases and human evolution
Authors: Guégan Jean-François , Prugnolle Franck , Thomas Frédéric
Published: April 2010

This chapter surveys global spatial patterns of the incidence of infectious diseases and human genetic variation. Contagious diseases are everywhere; zoonotic pathogens are concentrated in the tropics. Thus, populations in the tropics have suffered, and are still suffering, from a greater diversity of pathogens. Pathogens have exerted selective pressures on humans, which have evolved resistant genotypes. The results can be observed in human genomes. The life-history traits of early humans were shaped by interactions with parasites, and connections between life history traits and disease biology can help us to understand fertility, sexual dimorphism, and lifespan. Important questions remain open: which kinds of pathogens are most likely to emerge into human populations in the future? Will the homogenization of zoonotic diseases interfere with human adaptation and evolution? If pathogen pressure maintains much human polymorphism, what will be the effects of disease control and eradication on our own evolution?
Health consequences of ecogenetic variation
Authors: Bamshad Michael , Motulsky Arno G.
Published: April 2010

This chapter reviews human variation in drug response, taste perception, and nutritional effects. Such traits are often caused by multiple variants. New technologies and statistical methods make it easier to identify these variants. The frequencies and effects of many risk alleles influencing health co-vary more closely with ancestry than with race. While race captures substantial information about ancestry in U.S. populations, it is a poor predictor of individual ancestry proportions, which should be inferred from explicit genetic information. Clinicians need to understand the circumstances under which ancestry, rather than race, is a better predictor of disease risk or treatment outcome. There is a need to develop convenient, cheap ways to assess ancestry and to teach clinicians how to interpret ancestral information appropriately.
How hormones mediate trade-offs in human health and disease
Authors: Bribiescas Richard G. , Ellison Peter T.
Published: April 2010

Trade-offs between reproduction and maintenance can compromise health. Male hormones such as testosterone regulate energy allocation between reproductive effort and survival; this is made evident when immunological challenges cause changes in reproductive hormones. Female hormones adjust energy allocation between investment in ovarian function, somatic investment, and present offspring (lactation), implementing trade-offs between present and future reproduction. Metabolic hormones respond to environmental cues to sequester or liberate energetic resources such as glucose and fat. Mismatch between environmental conditions and the expression of metabolic hormones are likely to underlie variation in obesity and diabetes. Lifetime variation in endogenous reproductive hormones suggests a trade-off between early benefits for reproduction and later costs against survivorship expressed in population differences in the incidence of reproductive tumors, such as breast and prostate cancer.
Pathogen evolution in a vaccinated world
Authors: Read Andrew F. , Mackinnon Margaret J.
Published: April 2010

Vaccines alter the immune landscape experienced by pathogens, and hence their evolution, by targeting subsets of strains in a population, reducing the number of fully susceptible individuals, and creating or expanding classes of semi-immune hosts. The great success of vaccination against the acute childhood occurred without being undermined by pathogen evolution, but those diseases were easy targets: natural immunity was evolution-proof; all vaccination needed to do was to induce something very similar. Pathogens now under assault by vaccination are different: their natural infections induce leaky, often strain-specific immunity that usually wanes. Vaccines against these diseases will induce immunity to which natural selection has already found solutions. Evolutionary analysis is particularly warranted where vaccines are leaky, target subsets of strains or virulence determinants, involve novel technologies, or relax selection against virulence. Vaccination has been a great benefit. Continuing past successes requires evolutionary considerations at all stages of vaccine design and implementation.
Whole-genome analysis of pathogen evolution
Authors: Parkhill Julian
Published: April 2010

Whole-genome sequences for many bacterial species have initiated a new era of analysis. Horizontal gene exchange may be the dominant mechanism of adaptation. Bacterial chromosomes can be divided into core and accessory genes. Core genes are more likely to be involved in central processes such as transcription and translation, and are less likely to be horizontally exchanged. Accessory genes are more likely to be involved in adaptation and pathogenicity, and to have been horizontally acquired. Bacteria can evolve very rapidly in new niches, sometimes via genome degradation as well as gene acquisition. Many pathogenic bacteria have specialized mechanisms for generating diversity in otherwise clonal populations that are used to adapt to rapidly or randomly changing environments. Bacteria evolve under many selective pressures, not just the requirements of pathogenicity, including via ‘arms-races’ with their own parasites.
Emergence of new infectious diseases
Authors: Woolhouse Mark , Antia Rustom
Published: April 2010

This chapter reviews the evolution and ecology of emerging diseases. Human infectious diseases are caused by more than 1400 pathogen species with considerable diversity in lifestyles. Almost all pathogens of newly emerging diseases come from animal reservoirs. Most are viruses, especially RNA viruses. The emergence of a new infectious disease in the human population involves exposure to the pathogen, successful infection of the hosts, and sufficient transmission between hosts. These different levels of emergence make up the ‘pathogen pyramid’. Both ecological and evolutionary changes can affect a pathogen's position on the pyramid. HIV/AIDS, influenza (H5N1), SARS, Ebola, and monkeypox are emerging diseases. From the available data it is hard to tell if ecological changes alone caused these diseases to emerge or if evolutionary changes were sometimes involved as well. The past provides some guidelines as to which kinds of pathogen are most likely to emerge in the future.
Lifestyle, diet, and disease: comparative perspectives on the determinants of chronic health risks
Authors: Leonard William R.
Published: April 2010

We evolved under high levels of physical activity and energy expenditure, seasonal fluctuations in food availability, and frequent periods of marginal or negative energy balance. Today, we continue to eat about the same amount but exercise less, and the ‘imbalance’ between energy intake and expenditure causes obesity. Consumption of meat from feedlot animals now causes atherosclerosis; eating wild or grass-fed animals does not. For most of human history, simple carbohydrates were a minor element of our diet; today Americans derive almost 40% of calories from simple sugars and refined grain products. Simple carbohydrates contribute to the rise of type 2 diabetes in the industrialized world. The problems of ‘overnutrition’ and energy surplus are causing rates of obesity, diabetes, and hypertension to increase more rapidly in the developing than in the industrialized world. Nutritional interventions should promote increased exercise and activity levels as well as dietary modifications.
The evolutionary context of human aging and degenerative disease
Authors: Austad Steven N. , Finch Caleb E.
Published: April 2010

This chapter reviews evidence on human aging. Humans are the longest-lived primate. Trade-offs modulate human life span. ‘Longevity genes’ that protect against disease may slow the aging processes in humans and in model organisms, but they are not at high frequency in human populations, probably because they reduce fitness in early life. Insights into their protective mechanisms could yield pharmaceuticals that extend human health, but close attention would have to be paid to side effects, for the effects on humans of genetic alterations that extend life in laboratory mice are not pleasant. Genetic alterations in the GH/IGF-I axis appear at best not to extend life and at worst to shorten it, with many detrimental impacts on health. It would help to have a small, short-lived, primate research model in which anti-aging therapies developed from mouse experiments could be evaluated before testing them on humans.
Sorbaria sorbifolia is a New Host for Rhodococcus fascians
Authors: Miller Marilyn L. , Putnam Melodie L.
Published: April 2010

This work confirms S. sorbifolia as a newly identified host for R. fascians. This finding indicates woody plants may be at risk of disease in those nurseries that grow a range of woody and non-woody materials close together in the same location.

Accepted for publication 22 January 2010. Published 8 April 2010.
Sedation for oocyte retrieval using target controlled infusion of propofol and incremental alfentanil delivered by non‐anaesthetists
Authors: Edwards J. A. , Kinsella J. , Shaw A. , Evans S. , Anderson K. J.
Published: April 2010

Oocyte retrieval is a procedure where sedation is recommended. This paper presents the process of setting up a new, non‐anaesthetist delivered service in our institution, the development of safety systems and the audit data we have used to assure quality, effectiveness and safety. Logbook data were collected for 4342 cases, with detailed audit data collected for 260 cases. Safety is acceptable with a respiratory adverse incident rate of 0.5/1000 (95% CI 0.1–1.6/1000 cases). Unplanned, direct anaesthetic assistance was required in 3.5/1000 cases (95% CI 1.7–5.3/1000 cases). Anaesthetic advice was required in 7.5% cases (95% CI 4.2–10.7%) at the inception of the service, but rarely once established: 0.6% (95% CI 0.2–1.0%). Nearly all patients (99%) would have the same sedation method again, no patients required admission, and patients’ co‐operation was judged by the operating surgeon as very good or good in 91% of cases.
Vancomycin dosing assessment in intensive care unit patients based on a population pharmacokinetic/pharmacodynamic simulation
Authors: Revilla Natalia , Martín‐Suárez Ana , Pérez Marta Paz , González Félix Martín , Fernández de Gatta María del Mar
Published: April 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Despite the frequent use of vancomycin in intensive care unit (ICU) patients, few studies aimed at characterizing vancomycin population pharmacokinetics have been performed in this critical population.

• Population pharmacokinetics coupled with pharmacodynamic analysis, in order to optimize drug exposure and hence antibacterial effectiveness, has been little applied in these specific patients.

WHAT THIS STUDY ADDS

• Our population model characterized the pharmacokinetic profile of vancomycin in adult ICU patients, higher distribution volume values (V) being observed when the patient's serum creatinine (CrSe) was greater than 1 mg dl−1.

• Age and creatinine clearance (CLcr) were identified as the main covariates explaining the pharmacokinetic variability in vancomycin CL.

• Our pharmacokinetic/pharmacodynamic (PK/PD) simulation should aid clinicians to select initial vancomycin doses that will maximize the rate of response in the ICU setting, taking into account the patient's age and renal function as well as the susceptibility of Staphylococcus aureus.

AIM

To estimate the vancomycin pharmacokinetic profile in adult ICU patients and to assess vancomycin dosages for increasing the likelihood of optimal exposure.

METHODS

Five hundred and sixty‐nine concentration–time data from 191 patients were analysed using a population pharmacokinetic approach (NONMEN™). External model evaluation was made in 46 additional patients. The 24 h area under the concentration–time curve (AUC(0,24 h)) was derived from the final model. Minimum inhibitory concentration (MIC) values for S. aureus were obtained from the EUCAST database. AUC(0,24 h) : MIC ≥ 400 was considered as PK/PD efficacy index. The probability of different dosages attaining the target considering different strains of S. aureus and patient subgroups was estimated with Monte Carlo simulation.

RESULTS

Vancomycin CL showed a significant dependence on patient age and renal function whereas CrSe > 1 mg dl−1 increased V more than twofold. For our representative ICU patient, 61 years, 73 kg, CrSe= 1.4 mg dl−1, measured CLCr= 74.7 ml min−1, the estimated values were CL = 1.06 ml min−1 kg−1 and V= 2.04 l kg−1. The cumulative fraction of response for a standard vancomycin dose (2 g day−1) was less than 25% for VISA strains, and 33% to 95% for susceptible S. aureus, depending on patient characteristics.

CONCLUSIONS

Simulations provide useful information regarding the initial assessment of vancomycin dosing, the conventional dosing regimen probably being suboptimal in adult ICU patients. A graphic approach provides the recommended dose for any selected probability of attaining the PK/PD efficacy target or to evaluate the cumulative fraction of response for any dosing regimen in this population.
Effectiveness, safety and cost of drug substitution in hypertension
Authors: Johnston Atholl , Stafylas Panagiotis , Stergiou George S.
Published: April 2010

Cost‐containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost‐effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse‐event profiles of available alternative drugs, differences in the ‘inactive’ components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended.
Absence of large intragenic rearrangements in the DPYD gene in a large cohort of colorectal cancer patients treated with 5‐FU‐based chemotherapy
Authors: Paré Laia , Paez David , Salazar Juliana , Del Rio Elisabeth , Tizzano Eduardo , Marcuello Eugenio , Baiget Montserrat
Published: April 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Dihydropyrimidine dehydrogenase (DPD) is the enzyme responsible for the elimination of approximately 80% of the administered dose of 5‐fluorouracil (5‐FU).

• Mutations in the DPD‐coding gene have been shown to increase the risk of severe toxicity in 5‐FU treated patients.

• The IVS14+1G>A is the most common DPYD mutation.

WHAT THIS STUDY ADDS

• The intragenic rearrangements of DPYD using multiplex ligation‐dependent probe amplification (MLPA) were studied for the first time in a large series of 234 colorectal cancer patients treated with 5‐FU‐containing chemotherapy.

• No deletions or duplications of one or more DPYD exons were detected. The presence of the IVS14+1G>A mutation was also excluded.

• These data show that neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation are responsible for the serious toxicity associated with a 5‐FU containing regimen in this cohort of Spanish patients.

AIMS

To study the relationship between the toxicity associated with a 5‐FU‐based therapy and the presence of (i) the large intragenic rearrangements in the DPYD gene and (ii) the IVS14+1G>A mutation.

METHODS

We used the multiplex ligation‐dependent probe amplification technique (MLPA) to study genomic DNA from 234 colorectal cancer patients treated with 5‐FU‐based chemotherapy.

RESULTS

We did not detect any deletion/duplication in the DPYD gene. The presence of the IVS14+1G>A mutation was also excluded.

CONCLUSIONS

Neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation play a significant role in the development of serious toxicity associated with a 5‐FU containing regimen.
Spectrum of molecular defects in juvenile myelomonocytic leukaemia includes ASXL1 mutations
Authors: Sugimoto Yuka , Muramatsu Hideki , Makishima Hideki , Prince Courtney , Jankowska Anna M. , Yoshida Nao , Xu Yinyan , Nishio Nobuhiro , Hama Asahito , Yagasaki Hiroshi , Takahashi Yoshiyuki , Kato Koji , Manabe Atsushi , Kojima Seiji , Maciejewski Jaroslaw P.
Published: April 2010

Mutations in NF1, PTPN11, NRAS, KRAS and CBL have been reported to play a pathogenetic role in juvenile myelomonocytic leukaemia (JMML), a rare myelodyplastic/myeloproliferative neoplasm occurring in children. Recently, mutations in ASXL1 were identified in chronic myelomonocytic leukaemia and other myeloid malignancies. We sequenced exon 12 of ASLX1 in 49 JMML patients, and found 2 novel heterozygous (nonsense and frameshift) mutations, one occurring as a sole lesion, the other was in conjunction with a PTPN11 mutation. ASXL1 cooperates with KDM1A in transcriptional repression and thereby ASXL1 mutations may synergize with or mimic other JMML‐related mutations.
Optimizing legume content and forage yield of mown white clover–Italian ryegrass mixtures through nitrogen fertilization and grass row spacing
Authors: Annicchiarico P. , Tomasoni C.
Published: April 2010

Mixed swards of white clover–grass mixtures in highly productive environments often fail to reach the minimum recommended annual clover proportion of about 0·30. This study assessed the effect on clover content and total dry matter (DM) yield of two spring N applications (0 and 45 kg N ha−1) and two distances between drilled grass‐rows (0·18 and 0·36 m) over 3 years for mown swards of white clover–Italian ryegrass (Trifolium repens–Lolium multiflorum) in binary mixtures in northern Italy. An additional aim was to determine the advantage of association of grass–clover compared with grass and clover monocultures. On average, N fertilization of mixtures resulted in almost 9% higher total yield (P < 0·01; mean response = 18·1 kg of total DM per kg of N) but decreased the clover proportion (0·250 vs. 0·312). Wider grass‐row spacing increased clover proportion (0·327 vs. 0·234; P < 0·01) with no reduction of total DM yield. N fertilization × grass‐row spacing interaction occurred only for clover content (P < 0·01). Without N fertilization, mixtures out‐yielded clover and grass pure stands. With N fertilization, at double rate to pure grass, yields from mixtures were greater than from clover and comparable to Italian ryegrass.
Simvastatin induces Foxp3+ T regulatory cells by modulation of transforming growth factor‐β signal transduction
Authors: Kim Yong Chan , Kim Kee Kwang , Shevach Ethan M.
Published: April 2010

Statins are widely used drugs for the treatment of hypercholesterolaemia. A number of recent studies have suggested that statins also have pleiotropic effects on immune responses and statins have proven to be effective in the treatment of autoimmune diseases in animal models. Foxp3+ T regulatory cells are a unique subset of CD4+ T cells that mediate immunosuppression. Foxp3+ T cells develop in the thymus, but can also be induced in peripheral sites in the presence of transforming growth factor‐β (TGF‐β). We demonstrate here that simvastatin blockade of the mevalonate pathway can mediate induction of mouse Foxp3+ T cells and that simvastatin can synergize with low levels of TGF‐β to induce Foxp3+ T cells. The effects of simvastatin are secondary to a blockade of protein geranylgeranylation, are mediated at late time‐points after T‐cell activation, and are associated with demethylation of the Foxp3 promoter. One major effect of simvastatin was inhibition of the induction of Smad6 and Smad7, inhibitory Smads that inhibit TGF‐β signalling. Our results suggest that one mechanism responsible for the immunosuppressive effects of statins is the ability to promote the generation of Foxp3+ T regulatory cells.
Memory T‐cell trafficking: new directions for busy commuters
Authors: Marelli‐Berg Federica M. , Fu Hongmei , Vianello Fabrizio , Tokoyoda Koji , Hamann Alf
Published: April 2010

The immune system is unique in representing a network of interacting cells of enormous complexity and yet being based on single cells travelling around the body. The development of effective and regulated immunity relies upon co‐ordinated migration of each cellular component, which is regulated by diverse signals provided by the tissue. Co‐ordinated migration is particularly relevant to the recirculation of primed T cells, which, while performing continuous immune surveillance, need to promptly localize to antigenic sites, reside for a time sufficient to carry out their effector function and then efficiently leave the tissue to avoid bystander damage. Recent advances that have helped to clarify a number of key molecular mechanisms underlying the complexity and efficiency of memory T‐cell trafficking, including antigen‐dependent T‐cell trafficking, the regulation of T‐cell motility by costimulatory molecules, T‐cell migration out of target tissue and fugetaxis, are reviewed in this article.
DM influences the abundance of major histocompatibility complex class II alleles with low affinity for class II‐associated invariant chain peptides via multiple mechanisms
Authors: Rinderknecht Cornelia H. , Roh Sujin , Pashine Achal , Belmares Michael P. , Patil Namrata S. , Lu Ning , Truong Phi , Hou Tieying , Macaubas Claudia , Yoon Taejin , Wang Nan , Busch Robert , Mellins Elizabeth D.
Published: April 2010

DM catalyses class II‐associated invariant chain peptide (CLIP) release, edits the repertoire of peptides bound to major histocompatibility complex (MHC) class II molecules, affects class II structure, and thereby modulates binding of conformation‐sensitive anti‐class II antibodies. Here, we investigate the ability of DM to enhance the cell surface binding of monomorphic antibodies. We show that this enhancement reflects increases in cell surface class II expression and total cellular abundance, but notably these effects are selective for particular alleles. Evidence from analysis of cellular class II levels after cycloheximide treatment and from pulse‐chase experiments indicates that DM increases the half‐life of affected alleles. Unexpectedly, the pulse‐chase experiments also revealed an early effect of DM on assembly of these alleles. The allelically variant feature that correlates with susceptibility to these DM effects is low affinity for CLIP; DM‐dependent changes in abundance are reduced by invariant chain (CLIP) mutants that enhance CLIP binding to class II. We found evidence that DM mediates rescue of peptide‐receptive DR0404 molecules from inactive forms in vitro and evidence suggesting that a similar process occurs in cells. Thus, multiple mechanisms, operating along the biosynthetic pathway of class II molecules, contribute to DM‐mediated increases in the abundance of low‐CLIP‐affinity alleles.
Shade avoidance: an integral component of crop–weed competition
Authors: PAGE E R , TOLLENAAR M , LEE E A , LUKENS L , SWANTON C J
Published: April 2010

PageER, TollenaarM, LeeEA, LukensL & SwantonCJ (2010). Shade avoidance: an integral component of crop–weed competition.Weed Research50, 281–288.

Crop–weed competition is comprised of both resource dependent and resource independent processes. While many studies have focused on the role that resource dependant competition plays in reducing crop yields, few have investigated whether resource independent effects may contribute to these losses. In this study, we identify the red‐to‐far‐red ratio as a variable that contributing to resource independent competition and tested the hypothesis that the expression of shade avoidance in response to weeds reduces maize fitness (i.e., kernel number) in the absence of resource dependent competition. Seedlings were grown in a field fertigation system under two light quality environments: an ambient and a low red‐to‐far‐red ratio environment, which were designed to simulate weed‐free and weedy conditions respectively. Plants that expressed classic shade avoidance characteristics set fewer kernels per plant and partitioned less biomass to the developing ear. Shade avoidance also doubled the plant‐to‐plant variability in these yield parameters (i.e., kernel number and harvest index) without affecting the mean or frequency distribution of shoot biomass at maturity. We propose that shade avoidance should be viewed as an integral component of the process of competition. This resource independent response precedes and conditions the crop seedling for the onset of resource dependent competition.