bluuebunny/crossref_metadata_2025 huggingface dataset:
Organismic Spatiality: Toward a Metaphysic of Composition
Authors: Posteraro Tano S
Published: August 2014

The task of this paper is the construction of a theory of organismic spatiality. I take as a starting point Gilles Deleuze's reference in The Logic of Sense to Gilbert Simondon's concept of the membrane. The membrane is a dynamically topological limit between the organism's milieus of interiority and exteriority—the first moment of organismic spatiality. It is the foundation of the organism as an entity spatially distinct from its environment. The membrane is discriminatory and asymmetric—a concept, I claim, best understood by way of a discussion of affectivity. To understand how the membrane brings the organism's interior milieu into contact with the outside requires us to analyze its capacity to affect and be affected by its environment. To appreciate the compositional implications of this affectivity, I bring the concept into conversation with Humberto Maturana and Francisco Varela's work on autopoietic systems theory. Conceived autopoietically, the organism's activity as a living system constructs its own milieu of exteriority. Just as it pulses to its rhythm of temporality, so too does the organism live its own space: The here, as opposed to the now, of organismic subjectivity.
Vigorous Orientation Signal Propagates Best from Collinear Motion
Authors: Girelli Massimo
Published: August 2014

In the present study, the Poggendorff illusion was tested with four types of stimuli: A moving dot, a moving bar parallel to the inducing lines, a moving bar collinear to the motion trajectory, and static bars as in the classic illusion. Psychometric functions of the alignment task showed that the collinear bar, where orientation and motion trajectory matched, yielded the best alignment performance almost eliminating the illusion; the vertical bar, on the contrary, showed the worst alignment, finally the dot and the static bars led to intermediate alignments. These results demonstrate the interaction between orientation and motion trajectory that likely takes place in the primary visual cortex (V1) where these two signals might be modulated by top-down activity from higher order areas such as the middle temporal (MT). This vigorous orientation-motion trajectory interaction allows extremely accurate positional predictions of moving objects in the visual scene, in particular during occlusion.
Least-limiting water range of the soil seedbed submitted to mechanical and biological chiselling under no-till
Authors: Filho O. Guedes , da Silva A. P. , Giarola N. F. B. , Tormena C. A.
Published: August 2014

Physical quality of the soil seedbed affects germination, seedling emergence and crop establishment. The aim of this work was to determine the least-limiting water range (LLWR) of a soil seedbed cultivated for 18 consecutive years under no-till (NT) and submitted to mechanical chiselling (NT-M) and biological chiselling by a forage radish cover crop (NT-B). The study was carried out in Ponta Grossa, Paraná, Brazil. The experimental design was randomised complete blocks with four replications. Soil samples at 0–5 and 5–10 cm depths were collected at 6 and 18 months after the start of the experiment which corresponded to maize (October 2009) and soybean (November 2010) planting. Water-retention curve, penetration-resistance curve, soil and relative bulk density, and LLWR were determined. Bulk density did not differ among treatments at 0–5 cm depth for both evaluation periods. At 5–10 cm soil depth, the NT-M treatment showed the lowest bulk density at the first sampling (2009), whereas NT-B showed the highest bulk density at the second sampling (2010). Soil penetration resistance was the most limiting factor of the LLWR, which was greater in NT-M for both soil layers at the first sampling. At the second sampling, the NT treatment had the greatest LLWR at 0–5 cm, but at 5–10 cm soil depth, both NT and NT-M had higher LLWR than NT-B. The efficiency of mechanical chiselling in improving soil seedbed physical quality lasted 18 months after its application. Biological chiselling was efficient in improving soil air-filled porosity in both periods as evaluated by the LLWR.
Murine CD27
(−)
Vγ6
(+)
γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages
Authors: Rei Margarida , Gonçalves-Sousa Natacha , Lança Telma , Thompson Richard G. , Mensurado Sofia , Balkwill Frances R. , Kulbe Hagen , Pennington Daniel J. , Silva-Santos Bruno
Published: August 2014

Significance

Tumor development is impacted by a set of diverse infiltrating leukocyte populations that can either inhibit or, paradoxically, enhance tumor cell growth. This study characterizes a cellular cross-talk between γδ T lymphocytes and small peritoneal macrophages (SPMs) that is mediated by the proinflammatory cytokine, IL-17, and promotes ovarian cancer growth. IL-17 is preferentially produced by a population of γδ T cells, displaying a distinctive CD27
(−)
Vγ6
(+)
phenotype, that strongly proliferate in response to tumor challenge. This associates with the mobilization of SPMs that express protumor and proangiogenic molecular mediators upregulated by IL-17. Critically, these SPMs can directly enhance ovarian cancer cell growth. Our work identifies an IL-17–dependent γδ T cell/SPM axis that promotes tumor development and thus counteracts cancer immunosurveillance.
Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma
Authors: Lock Frances E. , Rebollo Rita , Miceli-Royer Katharine , Gagnier Liane , Kuah Sabrina , Babaian Artem , Sistiaga-Poveda Maialen , Lai C. Benjamin , Nemirovsky Oksana , Serrano Isabel , Steidl Christian , Karimi Mohammad M. , Mager Dixie L.
Published: August 2014

Significance

Sequences derived from transposable elements (TEs) are abundant in the human genome and can influence gene expression. In normal cells, most TEs are silenced by epigenetic mechanisms such as DNA methylation but, in cancer, normally dormant TEs can become active. We hypothesized that cancer-specific release of epigenetic suppression of TEs could result in gene expression perturbations, which could promote oncogenesis. Using a bioinformatics method, we identified many genes expressed in diffuse large B-cell lymphoma (DLBCL) via activation of TE promoters. Further analysis of one,
FABP7
, showed it was expressed in some DLBCL samples through use of a TE promoter. The TE-driven
FABP7
transcript encodes a novel isoform of the protein, which is required for optimal DLBCL cell line proliferation.
Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus
Authors: Yang Yang , Du Lanying , Liu Chang , Wang Lili , Ma Cuiqing , Tang Jian , Baric Ralph S. , Jiang Shibo , Li Fang
Published: August 2014

Significance

A constant and long-term threat to human health is cross-species transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) from bats to humans. However, this process is poorly understood. Examining the cross-species transmissibility of bat coronavirus HKU4, which is genetically related to MERS-CoV, can provide critical information about the likely causes of MERS-CoV infections in humans. Here we investigate the receptor usage and cell entry mechanism of HKU4 compared with MERS-CoV. Our results reveal that MERS-CoV has adapted to use human receptor and cellular proteases for efficient human cell entry, whereas HKU4 can potentially follow-up and also infect human cells. These findings are critical for evaluating emerging disease potentials of bat coronaviruses and for preventing and controlling their spread in humans.
Characterizing the proton loading site in cytochromecoxidase
Authors: Lu Jianxun , Gunner M. R.
Published: August 2014

Significance

The transmembrane proton gradient is the primary source of cellular energy. Cytochromecoxidase pumps protons uphill across the membrane using the energy released by the reduction of O2. Proton transport requires that residues change their proton affinity during the reaction cycle. Calculation of proton binding identifies a cluster of residues that bind and release a proton on each reduction of the active site. These residues can constitute a proton loading site. The heme propionic acids play the central role in proton loading. If the propionic acid proton affinity is too low, no protons will be loaded. The same proton-pumping mechanism can be used for each of the four redox steps carried out in the reaction cycle.
Vectored antibody gene delivery protects againstPlasmodium falciparumsporozoite challenge in mice
Authors: Deal Cailin , Balazs Alejandro B. , Espinosa Diego A. , Zavala Fidel , Baltimore David , Ketner Gary
Published: August 2014

Significance

Malaria caused byPlasmodium falciparumresults in the death of between 500,000 and 800,000 children per year and thus presents a major infectious disease threat to public health. Antibodies directed against the circumsporozoite protein of the infectious form of the parasite can preventP. falciparuminfection. Nevertheless, current candidate malaria vaccines do not elicit consistent, durable protection. Here we demonstrate that an alternative to conventional immunization, antibody gene delivery by a viral vector [vectored immunoprophylaxis (VIP)], can direct sustained expression of protective mAb in vivo and preventP. falciparuminfection in a rodent model. These studies provide a proof of principle for the use of VIP against the deadliest form of human malaria.
Demography, not inheritance, drives phenotypic change in hunted bighorn sheep
Authors: Traill Lochran W. , Schindler Susanne , Coulson Tim
Published: August 2014

Significance

Understanding the consequences that selective harvest has on a targeted trait, such as body size, is a great challenge. This is principally because it is difficult to evaluate the relative importance of the evolutionary and demographic factors that underlie a change in the distribution of a selected trait in a hunted population. Here we use a novel and recently developed two-sex integral projection model to tease apart the underlying demographic and evolutionary mechanisms of trait change in a trophy-hunted bighorn sheep population. We find that body size is weakly inherited and that subsequently demographic change, and not evolutionary change, as previously thought, is the principle driver of trait shifts in hunted bighorn sheep.
Drought stress variability in ancient Near Eastern agricultural systems evidenced by δ
13
C in barley grain
Authors: Riehl Simone , Pustovoytov Konstantin E. , Weippert Heike , Klett Stefan , Hole Frank
Published: August 2014

Significance

Collapse and resilience of ancient Near Eastern societies is intrinsically tied to agricultural production. Despite intensive palaeoclimate research, the role of environmental conditions in ancient agricultural production is little understood. Stable carbon isotope analysis on cereal grains from archaeological sites provides a direct evidence for drought stress. This paper demonstrates that drought stress correlated with major climatic fluctuations and affected many agricultural settlements in the ancient Near East but that its regional impact was diverse and influenced by geographic factors and human technology. The results lead to a better understanding of how ancient agricultural societies performed under fluctuating climate and regionally diverse environmental conditions.
Hybrid biosynthetic gene therapy vector development and dual engineering capacity
Authors: Jones Charles H. , Ravikrishnan Anitha , Chen Mingfu , Reddinger Ryan , Kamal Ahmadi Mahmoud , Rane Snehal , Hakansson Anders P. , Pfeifer Blaine A.
Published: August 2014

Significance

Vaccination is a powerful means of preempting or treating disease. The process depends on successful recognition of a foreign entity (an antigen) to elicit a strong immune response. The delivery of an antigen encoded as a DNA molecule (a genetic antigen) requires the assistance of a vector to facilitate the process of gene expression within immune system sentinels termed antigen-presenting cells (APCs). In this study, two normally distinct vectors (a bacterial cell and a synthetic polymer) were combined to generate a hybrid vector. The new vector coupled synergistic mechanisms to assist and improve gene delivery to APCs. Furthermore, the hybrid vector provides unique and complimentary engineering capabilities that were demonstrated to tailor and improve APC gene delivery further.
Rare earth elements activate endocytosis in plant cells
Authors: Wang Lihong , Li Jigang , Zhou Qing , Yang Guangmei , Ding Xiao Lan , Li Xiaodong , Cai Chen Xin , Zhang Zhao , Wei Hai Yan , Lu Tian Hong , Deng Xing Wang , Huang Xiao Hua
Published: August 2014

Significance

Because of their promotional effects on plant growth and development, rare earth elements (REEs) have been widely used in agriculture as plant growth stimulants. However, little is known about the cellular basis of REE actions in plants, and the biological safety of farm REE application in agriculture has not yet attracted enough attention. Here, we show that two types of REEs entered plant cells by endocytosis, and that they both had an activating effect on endocytosis. Moreover, we found that a portion of REEs was finally deposited in plant cells. Our data thus provide novel insights into the cellular mechanisms of REE actions in plants, and may also serve as valuable documentation for evaluating the biological safety of REE application in agriculture.
Ross and the particularism/generalism divide
Authors: Olsen Kristian
Published: August 2014

W. D. Ross is commonly considered to be ageneralistabout prima facie duty but aparticularistabout absolute duty. That is, many philosophers hold that Ross accepts that there are true moral principles involving prima facie duty but denies that there are any true moral principles involving absolute duty. I agree with the former claim: Ross surely accepts prima facie moral principles. However, in this paper, I challenge the latter claim. Ross, I argue, is no more a particularist about absolute duty than a utilitarian or a Kantian is. While this conclusion is interesting in its own right, it is also important, I argue, because it prevents us from overlooking Ross’s criterion of moral obligation and because it may have implications on the broader debate between particularists and generalists.
The Role of Structure: a critical notice of Sider’s Writing the Book of the World
Authors: Goswick Dana
Published: August 2014

I critically evaluate the notion of structure Ted Sider presents inWriting the Book of the World. A prerequisite to understanding Sider’s notion of structure is understanding Sider’s take on ideology and ontology. In Section II, I discuss this. In Section III, I consider arguments in favor of structure. In Section IV, I examine one debate that is considered by Sider to be nonsubstantive: the debate over modality. I conclude, in Section V, by examining the receptionWriting the Book of the Worldhas received in the philosophical community.
Dissecting the complement pathway in hepatic injury and regeneration with a novel protective strategy
Authors: Marshall Keely M. , He Songqing , Zhong Zhi , Atkinson Carl , Tomlinson Stephen
Published: August 2014

Liver resection is commonly performed under ischemic conditions, resulting in two types of insult to the remnant liver: ischemia reperfusion injury (IRI) and loss of liver mass. Complement inhibition is recognized as a potential therapeutic modality for IRI, but early complement activation products are also essential for liver regeneration. We describe a novel site-targeted murine complement inhibitor, CR2-CD59, which specifically inhibits the terminal membrane attack complex (MAC), and we use this protein to investigate the complement-dependent balance between liver injury and regeneration in a clinical setting of pharmacological inhibition. CR2-CD59 did not impact in vivo generation of C3 and C5 activation products but was as effective as the C3 activation inhibitor CR2-Crry at ameliorating hepatic IRI, indicating that the MAC is the principle mediator of hepatic IRI. Furthermore, unlike C3 or C5 inhibition, CR2-CD59 was not only protective but significantly enhanced hepatocyte proliferation after partial hepatectomy, including when combined with ischemia and reperfusion. Remarkably, CR2-CD59 also enhanced regeneration after 90% hepatectomy and improved long-term survival from 0 to 70%. CR2-CD59 functioned by increasing hepatic TNF and IL-6 levels with associated STAT3 and Akt activation, and by preventing mitochondrial depolarization and allowing recovery of ATP stores.
Voltage control of Ca2+ permeation through N-type calcium (CaV2.2) channels
Authors: Buraei Zafir , Liang Haoya , Elmslie Keith S.
Published: August 2014

Voltage-gated calcium (CaV) channels deliver Ca2+ to trigger cellular functions ranging from cardiac muscle contraction to neurotransmitter release. The mechanism by which these channels select for Ca2+ over other cations is thought to involve multiple Ca2+-binding sites within the pore. Although the Ca2+ affinity and cation preference of these sites have been extensively investigated, the effect of voltage on these sites has not received the same attention. We used a neuronal preparation enriched for N-type calcium (CaV2.2) channels to investigate the effect of voltage on Ca2+ flux. We found that the EC50 for Ca2+ permeation increases from 13 mM at 0 mV to 240 mM at 60 mV, indicating that, during permeation, Ca2+ ions sense the electric field. These data were nicely reproduced using a three-binding-site step model. Using roscovitine to slow CaV2.2 channel deactivation, we extended these measurements to voltages <0 mV. Permeation was minimally affected at these hyperpolarized voltages, as was predicted by the model. As an independent test of voltage effects on permeation, we examined the Ca2+-Ba2+ anomalous mole fraction (MF) effect, which was both concentration and voltage dependent. However, the Ca2+-Ba2+ anomalous MF data could not be reproduced unless we added a fourth site to our model. Thus, Ca2+ permeation through CaV2.2 channels may require at least four Ca2+-binding sites. Finally, our results suggest that the high affinity of Ca2+ for the channel helps to enhance Ca2+ influx at depolarized voltages relative to other ions (e.g., Ba2+ or Na+), whereas the absence of voltage effects at negative potentials prevents Ca2+ from becoming a channel blocker. Both effects are needed to maximize Ca2+ influx over the voltages spanned by action potentials.
Ion conduction and selectivity in acid-sensing ion channel 1
Authors: Yang Lei , Palmer Lawrence G.
Published: August 2014

The ability of acid-sensing ion channels (ASICs) to discriminate among cations was assessed based on changes in conductance and reversal potential with ion substitution. Human ASIC1a was expressed in Xenopus laevis oocytes, and acid-induced currents were measured using two-electrode voltage clamp. Replacement of extracellular Na+ with Li+, K+, Rb+, or Cs+ altered inward conductance and shifted the reversal potentials consistent with a selectivity sequence of Li ∼ Na > K > Rb > Cs. Permeability decreased more rapidly than conductance as a function of atomic size, with PK/PNa = 0.1 and GK/GNa = 0.7 and PRb/PNa = 0.03 and GRb/GNa = 0.3. Stimulation of Cl− currents when Na+ was replaced with Ca2+, Sr2+, or Ba2+ indicated a finite permeability to divalent cations. Inward conductance increased with extracellular Na+ in a hyperbolic manner, consistent with an apparent affinity (Km) for Na+ conduction of 25 mM. Nitrogen-containing cations, including NH4+, NH3OH+, and guanidinium, were also permeant. In addition to passing through the channels, guanidinium blocked Na+ currents, implying competition for a site within the pore. The role of negative charges in an external vestibule of the pore was evaluated using the point mutation D434N. The mutant channel had a decreased single-channel conductance, measured in excised outside-out patches, and a macroscopic slope conductance that increased with hyperpolarization. It had a weakened interaction with Na+ (Km = 72 mM) and a selectivity that was shifted toward larger atomic sizes. We conclude that the selectivity of ASIC1 is based at least in part on interactions with binding sites both within and internal to the outer vestibule.
Legislating Incentives for Attorney Representation in Civil Rights Litigation
Authors: Farhang Sean , Spencer Douglas M.
Published: August 2014

Congress routinely relies on private lawsuits to enforce its mandates. In this article, we investigate whether, when it does so, the details of the legislation can importantly influence the extent to which the private bar is mobilized to carry out the prosecutorial function. Using an original and novel data set based on review of archived litigation documents for cases filed in the Northern and Eastern Districts of California over the two decades spanning 1981–2000, we examine the effects of the Civil Rights Act of 1991, which increased economic damages available to Title VII job discrimination plaintiffs, on their ability to secure counsel. We find that over the course of the decade after passage, the law substantially increased the probability that Title VII plaintiffs would be represented by counsel and that in doing so it reversed a decade-long trend in the opposite direction.
Safety and Efficacy of Transition from Inhaled Treprostinil to Parenteral Treprostinil in Selected Patients with Pulmonary Arterial Hypertension
Authors: Preston Ioana R. , Feldman Jeremy , White James , Franco Veronica , Ishizawar David , Burger Charles , Waxman Aaron B. , Hill Nicholas S.
Published: August 2014

Guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend sequential add‐on therapy for patients who deteriorate or fail to improve clinically. However, it is not known whether these patients also benefit from transitioning from inhaled prostacyclins to parenteral prostacyclins. We sought to characterize PAH patients receiving inhaled treprostinil who were transitioned to parenteral treprostinil. We conducted a multicenter retrospective study at 7 PAH centers and collected reasons, methods, safety, and outcome of patients transitioned from inhaled treprostinil to parenteral treprostinil. Twenty‐six patients with pulmonary hypertension in group 1, 4, or 5 transitioned from inhaled treprostinil to parenteral treprostinil (10 intravenous, 16 subcutaneous). Twenty‐four patients were also on one or two oral therapies. Reasons for transition were clinical deterioration, lack of clinical improvement, and pregnancy (19, 6, and 1 patients, respectively). Transitions occurred in hospital, clinic, or home (17, 7, and 2 patients, respectively). Parenteral infusion was started after the last inhaled treatment at maintenance dose (13 patients), after the inhaled therapy was downtitrated to 18 μg (6 patients), or with an overlap of inhaled downtitration with parenteral uptitration (7 patients). The transition was safe; side effects included symptoms of prostacyclin overdose. Patients were followed for 3–18 months. At 3 months, 8 patients improved, 17 maintained their functional class, and 1 continued to deteriorate. In conclusion, selected PAH patients can be safely transitioned from inhaled treprostinil to parenteral treprostinil using a variety of methodologies in different settings with the expectation that patients will improve or at least remain clinically stable.
Denominator vectors and compatibility degrees in cluster algebras of finite type
Authors: Ceballos Cesar , Pilaud Vincent
Published: August 2014

We present two simple descriptions of the denominator vectors of the cluster variables of a cluster algebra of finite type, with respect to any initial cluster seed: one in terms of the compatibility degrees between almost positive roots defined by S. Fomin and A. Zelevinsky, and the other in terms of the root function of a certain subword complex. These descriptions only rely on linear algebra. They provide two simple proofs of the known fact that the

d
d

-vector of any non-initial cluster variable with respect to any initial cluster seed has non-negative entries and is different from zero.
Eukaryotic translation initiation factor eIF5 promotes the accuracy of start codon recognition by regulating Pi release and conformational transitions of the preinitiation complex
Authors: Saini Adesh K , Nanda Jagpreet S , Martin-Marcos Pilar , Dong Jinsheng , Zhang Fan , Bhardwaj Monika , Lorsch Jon R , Hinnebusch Alan G
Published: August 2014

eIF5 is the GTPase activating protein (GAP) for the eIF2·GTP·Met-tRNAiMet ternary complex with a critical role in initiation codon selection. Previous work suggested that the eIF5 mutation G31R/SUI5 elevates initiation at UUG codons by increasing GAP function. Subsequent work implicated eIF5 in rearrangement of the preinitiation complex (PIC) from an open, scanning conformation to a closed state at AUG codons, from which Pi is released from eIF2·GDP·Pi. To identify eIF5 functions crucial for accurate initiation, we investigated the consequences of G31R on GTP hydrolysis and Pi release, and the effects of intragenic G31R suppressors on these reactions, and on the partitioning of PICs between open and closed states. eIF5-G31R altered regulation of Pi release, accelerating it at UUG while decreasing it at AUG codons, consistent with its ability to stabilize the closed complex at UUG. Suppressor G62S mitigates both defects of G31R, accounting for its efficient suppression of UUG initiation in G31R,G62S cells; however suppressor M18V impairs GTP hydrolysis with little effect on PIC conformation. The strong defect in GTP hydrolysis conferred by M18V likely explains its broad suppression of Sui− mutations in numerous factors. We conclude that both of eIF5's functions, regulating Pi release and stabilizing the closed PIC conformation, contribute to stringent AUG selection invivo.
Rrd1p, an RNA polymerase II-specific prolyl isomerase and activator of phosphoprotein phosphatase, promotes transcription independently of rapamycin response
Authors: Sen Rwik , Malik Shivani , Frankland-Searby Sarah , Uprety Bhawana , Lahudkar Shweta , Bhaumik Sukesh R.
Published: August 2014

Rrd1p (resistance to rapamycin deletion 1) has been previously implicated in controlling transcription of rapamycin-regulated genes in response to rapamycin treatment. Intriguingly, we show here that Rrd1p associates with the coding sequence of a galactose-inducible and rapamycin non-responsive GAL1 gene, and promotes the association of RNA polymerase II with GAL1 in the absence of rapamycin treatment following transcriptional induction. Consistently, nucleosomal disassembly at GAL1 is impaired in the absence of Rrd1p, and GAL1 transcription is reduced in the Δrrd1 strain. Likewise, Rrd1p associates with the coding sequences of other rapamycin non-responsive and inducible GAL genes to promote their transcription in the absence of rapamycin treatment. Similarly, inducible, but rapamycin-responsive, non-GAL genes such as CTT1, STL1 and CUP1 are also regulated by Rrd1p. However, transcription of these inducible GAL and non-GAL genes is not altered in the absence of Rrd1p when the steady-state is reached after long transcriptional induction. Consistently, transcription of the constitutively active genes is not changed in the Δrrd1 strain. Taken together, our results demonstrate a new function of Rrd1p in stimulation of initial rounds of transcription, but not steady-state/constitutive transcription, of both rapamycin-responsive and non-responsive genes independently of rapamycin treatment.
Child-related characteristics predicting subsequent health-related quality of life in 8- to 14-year-old children with and without cerebellar tumors: a prospective longitudinal study
Authors: Bull Kim S. , Liossi Christina , Culliford David , Peacock Janet L. , Kennedy Colin R. ,   on behalf of the Children's Cancer and Leukaemia Group (CCLG)
Published: August 2014

Background

We identified child-related determinants of health-related quality of life (HRQoL) in children aged 8–14 years who were treated for 2 common types of pediatric brain tumors.

Methods

Questionnaire measures of HRQoL and psychometric assessments were completed by 110 children on 3 occasions over 24 months. Of these 110, 72 were within 3 years of diagnosis of a cerebellar tumor (37 standard-risk medulloblastoma, 35 low-grade cerebellar astrocytoma), and 38 were in a nontumor group. HRQoL, executive function, health status, and behavioral difficulties were also assessed by parents and teachers as appropriate. Regression modeling was used to relate HRQoL z scores to age, sex, socioeconomic status, and 5 domains of functioning: Cognition, Emotion, Social, Motor and Sensory, and Behavior.

Results

HRQoL z scores were significantly lower after astrocytoma than those in the nontumor group and significantly lower again in the medulloblastoma group, both by self-report and by parent-report. In regression modeling, significant child-related predictors of poorer HRQoL z scores by self-report were poorer cognitive and emotional function (both z scores) and greater age (years) at enrollment (B = 0.038, 0.098, 0.136, respectively). By parent-report, poorer cognitive, emotional and motor or sensory function (z score) were predictive of lower subsequent HRQoL of the child (B = 0.043, 0.112, 0.019, respectively), while age at enrollment was not.

Conclusions

Early screening of cognitive and emotional function in this age group, which are potentially amenable to change, could identify those at risk of poor HRQoL and provide a rational basis for interventions to improve HRQoL.
Standardized Electrolyte Supplementation and Fluid Management Improves Survival During Amphotericin Therapy for Cryptococcal Meningitis in Resource-Limited Settings
Authors: Bahr Nathan C. , Rolfes Melissa A. , Musubire Abdu , Nabeta Henry , Williams Darlisha A. , Rhein Joshua , Kambugu Andrew , Meya David B. , Boulware David R.
Published: August 2014

Background.  Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokalemia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa.

Methods.  Human immunodeficiency virus-infected, antiretroviral therapy naive adults with cryptococcal meningitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphotericin B deoxycholate induction treatment. Intravenous fluid use was intermittent in 2001–2002, and universal in 2006–2012. In 2001–2009, serum potassium (K+) was monitored on days 1, 7, and 14 of treatment with replacement (K+, Mg2+) per clinician discretion. In 2011–2012, K+ was measured on days 1, 5, and approximately every 48 hours thereafter with universal electrolyte (K+, Mg2+) supplementation and standardized replacement. Clinical outcomes were retrospectively compared between fluid and electrolyte management strategies.

Results.  With limited intravenous fluids, the 14-day survival was 49% in 2001–2002. With universal intravenous fluids, the 30-day survival improved to 62% in 2006–2010 (P = .003). In 2011–2012, with universal supplementation of fluids and electrolytes, 30-day cumulative survival improved to 78% (P = .021 vs 2006–2010 cohort). The cumulative incidence of severe hypokalemia (<2.5 mEq/L) decreased from 38% in 2010 to 8.5% in 2011–2012 with universal supplementation (P < .001).

Conclusions.  Improved survival was seen in a resource-limited setting with proactive fluid and electrolyte management (K+, Mg2+), as part of comprehensive amphotericin-based cryptococcal therapy.
A Leukocyte Score to Improve Clinical Outcome Predictions in Bacteremic Pneumococcal Pneumonia in Adults
Authors: Blot Mathieu , Croisier Delphine , Péchinot André , Vagner Ameline , Putot Alain , Fillion Aurélie , Baudouin Nicolas , Quenot Jean-Pierre , Charles Pierre-Emmanuel , Bonniaud Philippe , Chavanet Pascal , Piroth Lionel
Published: August 2014

Background.  Bacteremic pneumococcal pneumonia (BPP) is associated with high and early mortality. A simple procedure to predict mortality is crucial.

Methods.  All adult patients with BPP admitted from 2005 through 2013 to the University Hospital of Dijon, France, were enrolled to study 30-day mortality and associated factors, particularly leukocyte counts. A simple leukocyte score was created by adding 1 point each for neutropenia (<1500 cells/mm3), lymphopenia (<400), and monocytopenia (<200).

Results.  One hundred and ninety-two adult patients (mean age, 69 years; standard deviation [SD], 19 years) who had developed and were hospitalized for BPP (58% community-acquired) were included. The 30-day crude mortality rate was 21%. The mean Pneumonia Severity Index score was high at 127.3 (SD = 41.3). Among the 182 patients who had a white blood cell count, 34 (19%) had a high leukocyte score (≥2). Multivariate analysis revealed that mortality was significantly associated with a high leukocyte score (odds ratio, 6.28; 95% confidence interval, 2.35–16.78), a high respiratory rate, a low serum bicarbonate level, and an altered mental status (all P < .05). The leukocyte score was not significantly dependent on the previous state of immunosuppression, alcoholism, or viral coinfection, but it did correlate with an acute respiratory distress syndrome and a low serum bicarbonate level.

Conclusions.  This new leukocyte score, in combination with the well known predictive factors, seems of interest in predicting the risk of death in BPP. A high score correlated with organ dysfunction and probably reflects the level of immunoparalysis. Its predictive value has to be confirmed in other cohorts.
Agricultural Futures
Authors: Scoones Ian
Published: August 2014

Global assessments have become central to international debates on a range of key policy issues. They attempt to combine “expert assessment” with processes of “stakeholder consultation” in what are presented as global, participatory assessments on key issues of major international importance. This chapter focuses on the IAASTD—the International Assessment of Agricultural Knowledge, Science and Technology for Development—through a detailed analysis of the underlying knowledge politics involved, centered particularly on the controversy over genetically modified crops. Global assessments contribute to a new landscape of governance in the international arena, offering the potential for links between the local and the global and new ways of articulating citizen engagement with global processes of decision making and policy. The chapter argues that in global assessments the politics of knowledge need to be made more explicit and that negotiations around politics and values must be put center stage. The black-boxing of uncertainty, or the eclipsing of more fundamental clashes over interpretation and meaning, must be avoided for processes of participation and engagement in global assessments to become more meaningful, democratic, and accountable. A critique is thus offered of simplistic forms of deliberative democratic practice and the need to “bring politics back in” is affirmed.
Power and the People in Russia
Authors: Hosking Geoffrey
Published: August 2014

Whereas many European states sought to dominate corporate associations in order to exploit their resources, the Russian monarchy had to create them in the late eighteenth century in order to transmit its own authority. Both before and after that, however, the Tsars mediated authority downwards through persons rather than institutions. This chapter highlights the paradoxes of a system which compensated for under-institutionalization through the workings of competing elite patron-client networks and small-scale popular communities of joint responsibility which survived long beyond 1917. Communists may have transformed and modernized society in appearance, but in reality that modernization perpetuated or even restored some of the archaic practices of pre-revolutionary society. The Soviet state, like the Tsarist one, depended on archaic social arrangements which lubricated its everyday functioning, but frustrated its ultimate purposes. Even at the start of the twenty-first century Russian politics were still in thrall to personalized power factions.
Geopolitics
Authors: LeDonne John P.
Published: August 2014

Powers, great and small, cannot overcome their geography; great powers cannot resist practising geopolitics. The makers of Russian geopolitics always had a sense that the mastery of space was fundamental to the exercise of power; that space meant the great river and sea basins constituting the Eurasian amphitheatre; and that the purpose of geopolitics was to restructure the Eurasian space in such a way that Moscow would become its political, economic and civilizational centre. Analysing the inter-relationships between geography, foreign policy, clientele politics and economic development, this chapter charts the ways in which successive Russian elites attempted to achieve that aim.
Russia and the West
Authors: Lovell Stephen
Published: August 2014

Concentrating on the political and cultural capital that various elites have extracted from notions of the West, this chapter identifies four phases in the development of the most consistently articulated binary opposition in modern Russian culture: Russia’s entry into the European state system in the late seventeenth and eighteenth centuries; the era of national awakening from the Napoleonic wars to the 1860s; the era of mass national politics and decolonization from the 1860s to the 1950s; and the era of American hegemony, globalization and European peace from the 1950s onwards which has eventually caused the Russian nation to reinvent itself in a postcommunist guise.
Imperial Defence
Authors: Lieven Dominic
Published: August 2014

Contrary to the influential myth propagated by Tolstoy’s War and Peace, the Russian war effort in 1812–14 was in reality intelligently conceived and purposefully executed under the overall direction of Alexander I, who was his own foreign minister and also played a significant role in military planning. Having analysed the strengths and weaknesses of the Russian armies, the efficiency of their supply lines, the mobilization of Russian manpower, and the significance of the Russian horse industry, the chapter concludes by examining the consequences of victory over Napoleon. Russian backwardness as revealed in the Crimean War owed less to the failings of Nicholas I than to the fact that the Industrial Revolution originated on Europe’s Western periphery and then took several generations to extend first to central and then to southern and eastern regions of the continent.
The Natural Course of Substance Use and Dependence
Authors: Jackson Kristina M. , Sartor Carolyn E.
Published: August 2014

Substance use and substance use disorders show normative epidemiological age-related trends, with typically onset in the late adolescent to young adult years, manifesting peak prevalences in emerging adulthood, and decreasing thereafter. Although less prevalent in older adults, substance misuse is more consequential when present and thus represents a public health concern. Careful examination of the population-based empirical literature indicates the necessity of viewing substance involvement in the context of development, with unique developmental factors associated with its onset, course, and resolution. Many individuals who suffer from a substance use disorder appear to “recover” without formal treatment. Despite normative age-related trends, there is considerable individual course variation, and modern statistical techniques have identified several distinct prototypic courses that appear to differ in their determinants and consequences. Research using a lifespan perspective on substance use and misuse has powerful implications for the design of effective, developmentally informed prevention and intervention programs.
Passion’s Slave?
Authors: Wiers Reinout W. , Field Matt , Stacy Alan W.
Published: August 2014

This chapter reviews the literature on cognitive processes in substance use disorders from a dual-process perspective. In dual-process models, behavior is viewed as the joint outcome of “impulsive” and “reflective” processes. Reflective processes rely on a single limited capacity mechanism and can be depleted, resulting in a stronger influence of impulsive processes. Recent studies confirmed this, both for state variables (e.g., reduced moderation of impulses after acute alcohol) and for trait variables (stronger prediction of addictive and related behaviors by impulsive processes in individuals with relatively weak executive control processes). In addiction, the balance between impulsive and reflective processes can become (further) disturbed as a result of the effects of the psychoactive substances on the cognitive processes involved. This is related to the notion of reduced “willpower,” traditionally at the heart of definitions of addiction. A model on the cognitive processes involved in addiction is presented, along with implications for interventions.
Mechanisms of Action of Different Drugs of Abuse
Authors: McCracken Lindsay M. , McCracken Mandy L. , Harris R. Adron
Published: August 2014

Drugs of abuse represent a spectrum of chemically diverse compounds that are used via various routes of drug administration depending on the drug and its preparation. Although the exact molecular mechanisms by which these agents act to produce their intoxicating effects are not completely understood, many drugs of abuse are known to bind to specific neuronal membrane proteins that produce effects on cellular signaling and ultimately on behavior. With repeated administration of a drug, individuals often develop tolerance, and discontinuation of drug use following chronic administration typically results in withdrawal symptoms. This chapter describes the mechanism of action for the following classes of drugs of abuse: alcohol, cannabinoids, hallucinogens, inhalants, nicotine, opioids, sedative hypnotics, and stimulants. In addition, mechanisms of tolerance and withdrawal are discussed.
Substance Use and Race and Ethnicity
Authors: McKinney Christy , Caetano Raul
Published: August 2014

Patterns of alcohol and drug use vary across race/ethnicity and according to type of alcohol or drug use. Notable differences across race/ethnicity exist for estimates of current drinking, level of drinking, binge drinking, alcohol abuse and/or dependence, beverage preference, driving while under the influence of alcohol, illicit drug use, alcohol or drug treatment, and alcohol-related adverse outcomes. Across race/ethnicity, substance use varies over sex, age, time, and level of acculturation. Although this variation is often similar across race/ethnicity (e.g., men drink more than women, the young more than the old), the magnitude of these differences is greater among some race/ethnicity groups. Race/ethnicity also plays a key role in substance use-related outcomes; some groups experience a disproportionate burden of alcohol-related ailments such as certain cancers, comorbid psychiatric conditions, or violence.
Serious Mental Illness
Authors: Mueser Kim T. , Noordsy Douglas L. , Drake Robert E.
Published: August 2014

The high comorbidity between substance use disorders and serious mental illnesses is a significant challenge to traditional treatment systems that have historically treated psychiatric and substance use disorders with different providers and agencies. Defining characteristics of serious mental illness include difficulty with work, performing in school or parenting, social difficulties, and problems caring for oneself. Common serious psychiatric disorders include schizophrenia, schizoaffective disorder, bipolar disorder, and severe major depression, posttraumatic stress disorder, and borderline personality disorder. The epidemiology of substance use disorders in serious mental illness is reviewed, including prevalence, correlates, and onset and course of the disorder. The clinical consequences of substance use disorders in this population are devastating for every possible aspect of the illness. Common factors may increase vulnerability to both substance abuse and psychiatric disorders. The principles of treating co-occurring disorders are based on modern integrated methods, as well as research on the effectiveness of integrated treatment.
Racial Redistricting and Descriptive Representation
Authors: Canon David T.
Published: August 2014

For most of our nation’s history, redistricting produced a partisan struggle as the two major parties tried to gain electoral advantage. In the past several decades, however, racial representation emerged as an important element of the redistricting process. The scholarly literature on this topic has examined three related questions: what role should racial redistricting play in the representation of racial interests, how may racial redistricting be used, and what is the connection between descriptive representation and the substantive representation of racial interests? The normative questions concerning how racial interests should be represented and empirical questions concerning how they are represented are discussed by other scholars in this volume. This essay will instead focus on the empirical and legal questions concerning the use of redistricting to produce descriptive representation.
Comparative Politics and American Political Development
Authors: Morgan Kimberly J.
Published: August 2014

The subfields of comparative politics and American political development (APD) have many intellectual affinities, as APD brought many of the questions and methods of comparative politics to the study of the US. In recent years, however, the two subfields have gone down separate research pathways, owing to the decline of political development as an area of study in comparative politics, the growing prevalence of large-Nresearch, and the specialization, and isolation, of academic subfields. However, two areas in which comparative politics and APD have had extensive dialogue—qualitative methodology and the welfare state—show there is much to gain from greater linkages between the two subfields. Fruitful dialogue could take place in other areas, including the study of state-building, democratization, and ethnic politics.
Developmental Pragmatics
Authors: Rollins Pamela Rosenthal
Published: August 2014

This chapter traces the development of communicative intention, conversation, and narrative in early interaction from infancy to early childhood. True communicative intention commences once the infant acquires the social cognitive ability to share attention and intention with another. The developing child’s pragmatic understanding is reflective of his/her underlying motivations for cooperation and shared intentionality. As children begin to understand others’ mental states, they can take others’ perspectives and understand what knowledge is shared and with whom, moving from joint perceptual focus to more decontextualized communicative intentions. With adult assistance, the young child is able to engage in increasingly more sophisticated conversational exchanges and co-constructed narratives which influence the child’s autonomous capabilities.
Continental European Perspective View
Authors: Verschueren Jef
Published: August 2014

This chapter questions the accuracy of the contrast between an Anglo-American component view and a Continental European perspective view of pragmatics. The latter is described as a necessarily interdisciplinary approach to linguistic pragmatics as a general science of language use. The question of possible unity in this wide field is addressed, concentrating mainly on the notions of implicitness, variability, negotiability, and adaptability. The chapter concludes with reference to a dividing line that is deemed more important in the light of recent developments: the contrast between strongly Western-based conceptualizations of language use and views that are rooted in non-Western cultures and societies.