bluuebunny/crossref_metadata_2025 huggingface dataset:
The implementation of evidence-based rehabilitation services for stroke survivors living in the community: the results of a Delphi consensus process
Authors: Fisher Rebecca J , Walker Marion F , Golton Ian , Jenkinson Damian
Published: February 2013

Background:

Recovery from stroke requires the provision of specialist rehabilitative care, yet there is a lack of research evidence on optimal methods of delivery and inequitable service provision across countries. Following consensus on Early Supported Discharge, our aim was to define core components of evidence-based community stroke services.

Design:

We used a modified Delphi approach with a purposive sample of 26 UK-based expert panellists (10 academics, 15 stroke service leads or commissioners, one stroke survivor). Statements based on research literature and policy documents were generated by an independent, mixed academic and service improvement team of nine. In three rounds of consultation panellists indicated their level of agreement with statements. Free text comments were analysed thematically.

Results:

Consensus of opinion (>70% agreement) was obtained on 76 of 80 statements. Panellists agreed that stroke specialist care tailored to clinical need should be provided following discharge from hospital. Flexible care pathways should be commissioned and provided through strategic and collaborative leadership across health and social care. Teams need to deliver stroke specialist rehabilitation, handing over responsibility to non-specialist services when patient rehabilitation goals have been met. Lack of consensus on whether to provide services exclusively for stroke patients and the need of support for carers highlights areas for further research.

Conclusions:

Consensus on the provision of evidence-based community stroke rehabilitation has been reached. Commissioning services with a clearly defined remit, which can deliver tailored care to individual stroke patients, is a challenge that needs further exploration.
Expression of dendritic cell lysosome-associated membrane protein and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin in condyloma acuminatum lesions
Authors: Ma Wei-Yuan , Zhuang Le , Qi Qi-Chao , Sun Qing
Published: February 2013

Objective

Retrospective, observational study to explore the role of dendritic cells (DCs) in condyloma acuminatum lesions (genital warts) and their relationship with duration of the disease.

Methods

Condyloma acuminatum lesion samples were collected from male patients with the condition and compared with normal foreskin samples from male volunteers. Cellular locations of dendritic cell lysosome-associated membrane protein (DC-LAMP) and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) were detected using immunohistochemistry. Levels of both proteins were determined using Western blot analysis; levels of their corresponding mRNAs were measured using reverse transcription–polymerase chain reaction.

Results

The mRNA and protein levels of DC-LAMP and DC-SIGN were both significantly higher in condyloma acuminatum lesions ( n = 30 samples) compared with normal skin samples ( n = 13). Levels of DC-LAMP and DC-SIGN protein and duration of disease were inversely correlated.

Conclusions

DC-LAMP and DC-SIGN may be involved in the pathogenesis of condyloma acuminatum. Their levels were inversely correlated with the duration of disease, suggesting that DCs might be involved in human papillomavirus clearance.
The “Hybrid Hero” in Western Dime Novels
Authors: Moon Cameron Elizabeth , Ogle Jennifer Paff
Published: February 2013

The purpose of this narrative inquiry was to explore how dress - including cross-dressing and androgynous dress - was used within the Deadwood Dick series to construct meanings about gender and identity. The research was informed by the works of Judith Butler and Erving Goffman and by reflection theory. Data were collected by extracting references to dress within five Deadwood Dick novels featuring Calamity Jane. Analyses revealed overarching themes related to traditionally feminine dress, androgynous dress, and cross-dressing. Transitions in ideological views of 19th century womanhood are reflected in the dime novels' alterations in appearance and gender performance that enabled female characters to act in expanded spheres. Androgyny allowed characters to adopt nontraditional gender identities, giving the freedom to participate in male-dominated contexts. Cross-dressing provided characters a means of navigating temporary changes in space and place. Findings provide a reflection of the evolving national character present in 19th century American society.
Injection-moulded biocomposites from polylactic acid (PLA) and recycled carbon fibre
Authors: Chen Richard , Misra Manjusri , Mohanty Amar K
Published: February 2013

The properties of injection-moulded polylactic acid (PLA) and recycled carbon fibre composites are examined in this study. Measurement of tensile, flexural, and impact resistance properties quantify the mechanical properties of the composites with increased fibre loading. Tensile strength and modulus of PLA and 30 wt% carbon fibre composite were found to increase by 73% and 438%, while flexural strength and modulus of carbon fibre composite increased by 53% and 400% compared to neat PLA. Consequently, storage modulus measured by dynamic mechanical analysis also improved with the addition of carbon fibre. Mechanical properties were correlated with the Hirsch model. Composite morphological study through scanning electron microscopy (SEM) showed pullout and partial wetting of fibre by matrix along with agglomeration. Differential scanning calorimetry study of the composites showed minor increase in relative crystallinity and crystallization temperature, while melting and cold crystallization temperatures were found to decrease due to the high-thermal conductivity of carbon fibre.
Power and Reduced Temporal Discounting
Authors: Joshi Priyanka D. , Fast Nathanael J.
Published: February 2013

Decision makers generally feel disconnected from their future selves, an experience that leads them to prefer smaller immediate gains to larger future gains. This pervasive tendency is known as temporal discounting, and researchers across disciplines are interested in understanding how to overcome it. Following recent advances in the power literature, we suggest that the experience of power enhances one’s connection with the future self, which in turn results in reduced temporal discounting. In Study 1, we found that participants assigned to high-power roles were less likely than participants assigned to low-power roles to display temporal discounting. In Studies 2 and 3, priming power reduced temporal discounting in monetary and nonmonetary tasks, and, further, connection with the future self mediated the relation between power and reduced discounting. In Study 4, experiencing a general sense of power in the workplace predicted actual lifetime savings. These results have important implications for future research.
Paleosecular variations refining the chronology of the sediments from the Pearl River Delta, southern China
Authors: Yang Xiaoqiang , Yang Jie , Su Zhihua , Huang Wenya , Wang Jianhua
Published: February 2013

A high-resolution paleosecular variations record since ~6 kyr, including direction and relative intensity, was derived from the Pearl River delta (PRD) sediments in southern China constrained by the radiocarbon ages in this paper. The comparison of both direction and relative intensity with other adjacent records confirmed that the non-dipole field has common fluctuations in the centennial to millennial timescales. This pattern provides some profound tied points to correlate the sediment sequence in the different deposition environments. The significant age offsets of the similar secular variation features between the different records corroborate the radiocarbon errors in dating the sediments. This work further showed that the geomagnetic secular variations can serve as an effective tool to determine the sediments’ age and correlate the stratigraphy for the different deposition environments in a wide region.
Coinfection by Vaccinia virus and an Orf virus–like parapoxvirus in an outbreak of vesicular disease in dairy cows in midwestern Brazil
Authors: Sant’Ana Fabiano J. F. de , Leal Fábio A. A. , Rabelo Rogério E. , Vulcani Valcinir A. S. , Moreira Carlos A. , Cargnelutti Juliana F. , Flores Eduardo F.
Published: February 2013

The current report describes an outbreak of vesicular disease affecting dairy cows in midwestern Brazil in which a coinfection with 2 poxviruses— Vaccinia virus (VACV) and a parapoxvirus—was demonstrated. Milking cows presented vesicles, painful reddish or whitish papules, and scabby proliferative lesions in the teats and udder, in a clinical course of approximately 10–21 days. Histologically, multifocal areas of moderate to severe acanthosis, spongiosis, hypergranulosis, and parakeratotic or orthokeratotic hyperkeratosis with adjacent focally extensive ulcers were observed in the epidermis. Rounded eosinophilic inclusion bodies were observed in the cytoplasm of epithelial cells of areas with acanthosis or necrosis. Moderate inflammatory infiltrate of lymphocytes, plasma cells, neutrophils, and macrophages were observed in some dermal areas. Two people milking the affected cows developed lesions on the hands, painful papules which progressed to ulcerative and scabby lesions in 4–7 days. Electron microscopy of scabs from 1 cow revealed the concomitant presence of orthopoxvirus and parapoxvirus particles. Scabs from 2 cows were positive by polymerase chain reaction for the parapoxvirus B2L gene; 1 of the scabs was also positive for the VACV vgf gene. Nucleotide sequencing of the B2L amplicon revealed a similarity of 96–99% with Orf virus (ORFV) and lower identity with Pseudocowpox virus (92–95%) and Bovine papular stomatitis virus (85–86%). Nucleotide sequencing of a region of parapoxvirus DNA polymerase gene revealed a high similarity (98–100%) with ORFV sequences. Thus, an unusual coinfection with VACV and a parapoxvirus, likely ORFV, was demonstrated in the outbreak.
Validation of Family, School, and Peer Influence on Volunteerism Scale Among Adolescents
Authors: Law Ben M. F. , Shek Daniel T. L. , Ma Cecilia M. S.
Published: February 2013

Social systems, particularly family, school, and peer, are especially critical in influencing adolescents to participate in volunteer service; however, no objective measures of this construct exist.

Objectives:

This study examined the psychometric properties of the Family, School, and Peer Influence on Volunteerism scale (FSPV) among Chinese adolescents. The FSPV is an instrument that assesses the perceived influence of these social systems on adolescent volunteerism. There are nine identical items for each of the three systems.

Method:

The FSPV was administered to 2,819 early adolescents in Hong Kong.

Results:

Confirmatory factor analyses revealed four factors, namely, “Family,” “School,” “Peer,” and “Extrinsic influence.” The FSPV also demonstrated good internal consistency, construct validity, and criterion-related validity.

Conclusion:

The psychometric properties of FSPV are adequate in the assessment of the perceived influence of social systems on volunteer service participation in Chinese adolescents.
Commemorative acts as discursive resources of historical identity
Authors: Mininni Giuseppe , Manuti Amelia , Curigliano Graziana
Published: February 2013

Discourse plays a crucial role in determining how both persons and communities shape social reality and attribute meaning to experience ( Edwards, 1997 ). This potential is mostly evident when the contended object of discourse is history itself, which is a peculiar area of the cultural mind. Hence, the discursive management of the collective tends to generate interpretations which in turn might mould personal and social identities. Sharing the spirit of the “innovations” brought about by cultural psychology (Valsiner, 2009), the present paper is intended to highlight how institutional and public discourses communicate different degrees of responsibility for the history of their own national group and, at the same time, how individuals construe historical identities with different degrees of guilt towards past events. Through a qualitative approach—the “diatextual analysis” (Mininni, 1992, 2001, 2005)—this paper proposes to investigate the rhetorical strategies adopted on occasion of some important commemorative events by the institutional spokesmen, as well as by the public opinion, to elaborate both positive and negative histories of their ingroup.
Determinants of Secondary Market Sales Prices for National Football League Personal Seat Licenses and Season Ticket Rights
Authors: Salaga Steven , Winfree Jason A.
Published: February 2013

A strong secondary market has emerged where National Football League (NFL) personal seat licenses (PSL) and season ticket rights (STR) are sold electronically. These data allow us to estimate determinants of market prices for long-run access to NFL attendance. The analysis finds that high-quality seating locations are a strong determinant of price. Clear differences exist between PSL and STR markets in regard to both general interest in the live NFL product and the effect of team quality on market price. Furthermore, we find that higher face value ticket prices are associated with lower secondary market PSL and STR sales prices.
Expression of innate immune genes, proteins and microRNAs in lung tissue of pigs infected experimentally with influenza virus (H1N2)
Authors: Skovgaard Kerstin , Cirera Susanna , Vasby Ditte , Podolska Agnieszka , Breum Solvej Ø , Dürrwald Ralf , Schlegel Michael , Heegaard Peter MH
Published: February 2013

This study aimed at providing a better understanding of the involvement of innate immune factors, including miRNA, in the local host response to influenza virus infection. Twenty pigs were challenged by influenza A virus subtype H1N2. Expression of microRNA (miRNA), mRNA and proteins were quantified in lung tissue at different time points after challenge (24 h, 72 h and 14 d post-infection (p.i.). Several groups of genes were significantly regulated according to time point and infection status including pattern recognition receptors (TLR2, TLR3, TLR7, retinoic acid-inducible gene I, melanoma differentiation associated protein-5), IFN and IFN-induced genes (IFN-β, IFN-γ, IRF7, STAT1, ISG15 and OASL), cytokines (IL-1 β, IL-1RN, IL-6, IL-7, IL-10, IL-12A, TNF-α, CCL2, CCL3 and CXCL10) and several acute phase proteins. Likewise, the following miRNAs were differentially expressed in one or more time groups compared with the control pigs: miR-15a, miR-21, miR-146, miR-206, miR-223 and miR-451. At d 1 p.i. lung tissue protein levels of IL-6, IL-12 and IFN-α were significantly increased compared with the control group, and haptoglobin and C-reactive protein were significantly increased at d 3 p.i. Our results suggest that, in addition to a wide range of innate immune factors, miRNAs may also be involved in controlling acute influenza infection in pigs.
The effects of actuator selection on non-volitional postural responses to torso-based vibrotactile stimulation
Authors: Lee Beom-Chan , Martin Bernard J , Sienko Kathleen H
Published: February 2013

Background

Torso-based vibrotactile feedback may significantly reduce postural sway in balance-compromised adults during quiet standing or in response to perturbations. However, natural non-volitional postural responses to vibrotactile stimulation applied to the torso remain unknown.

Methods

The primary goal of this study was to determine, for two types of actuators (tactors) and in the absence of instruction, whether vibrotactile stimulation induces a directional postural shift as a function of stimulation location. Eleven healthy young adults (20 – 29 years old) were asked to maintain an upright erect posture with feet hip-width apart and eyes closed. Two types of tactors, Tactaid and C2, which differ in design and stimulation strength, were placed on the skin over the right and left external oblique, internal oblique, and erector spinae muscles in a horizontal plane corresponding approximately to the L4/L5 level. Each tactor of the same type was activated twice randomly for each individual location and twice simultaneously for all locations at a frequency of 250 Hz for a period of 5 s.

Results

Vibration applied over the internal oblique and erector spinae muscle locations induced a postural shift in the direction of the stimulation regardless of the tactor type. For the aforementioned four locations, the root-mean-square (RMS) and power spectral density (PSD) of the body sway in both the A/P and M/L directions were also significantly greater during the vibration than before or after, and were greater for the C2 tactors than for the Tactaid tactors. However, simultaneous activation of all tactors or those over the external oblique muscle locations did not produce significant postural responses regardless of the tactor type.

Conclusion

The results suggest that the use of a torso-based vibrotactile sensory augmentation display should carefully consider the tactor type as well as the instruction of corrective movements. Attractive instructional cues (“move in the direction of the vibration”) are compatible with the observed non-volitional response to stimulation and may facilitate postural adjustments during vibrotactile biofeedback balance applications.
Short-term role of the dietary total antioxidant capacity in two hypocaloric regimes on obese with metabolic syndrome symptoms: the RESMENA randomized controlled trial
Authors: Lopez-Legarrea Patricia , de la Iglesia Rocio , Abete Itziar , Bondia-Pons Isabel , Navas-Carretero Santiago , Forga Lluis , Martinez J Alfredo , Zulet M Angeles
Published: February 2013

Background

Dietary strategies seem to be the most prescribed therapy in order to counteract obesity regarding not only calorie restriction, but also bioactive ingredients and the composition of the consumed foods. Dietary total antioxidant capacity (TAC) is gaining importance in order to assess the quality of the diet.

Methods

Ninety-six obese adults presenting metabolic syndrome (MetS) symptoms completed an 8-week intervention trial to evaluate the effects of a novel dietary program with changes in the nutrient distribution and meal frequency and to compare it with a dietary pattern based on the American Heart Association (AHA) guidelines.

Anthropometric and biochemical parameters were assessed at baseline and at the endpoint of the study, in addition to 48-hours food dietary records.

Results

Both diets equally (p > 0.05) improved MetS manifestations. Dietary TAC was the component which showed the major influence on body weight (p = 0.034), body mass index (p = 0.026), waist circumference (p = 0.083) and fat mass (p = 0.015) reductions. Transaminases (ALT and AST) levels (p = 0.062 and p = 0.004, respectively) were associated with lower TAC values.

Conclusion

RESMENA diet was as effective as AHA pattern for reducing MetS features. Dietary TAC was the most contributing factor involved in body weight and obesity related markers reduction.

Trial registration

http://www.clinicaltrials.gov; NCT01087086
Regulation of protein translation initiation in response to ionizing radiation
Authors: Trivigno Donatella , Bornes Laura , Huber Stephan M , Rudner Justine
Published: February 2013

Background

Proliferating tumor cells require continuous protein synthesis. De novo synthesis of most proteins is regulated through cap-dependent translation. Cellular stress such as ionizing radiation (IR) blocks cap-dependent translation resulting in shut-down of global protein translation which saves resources and energy needed for the stress response. At the same time, levels of proteins required for stress response are maintained or even increased. The study aimed to analyze the regulation of signaling pathways controlling protein translation in response to IR and the impact on Mcl-1, an anti-apoptotic and radioprotective protein, which levels rapidly decline upon IR.

Methods

Protein levels and processing were analyzed by Western blot. The assembly of the translational pre-initiation complex was examined by Immunoprecipitation and pull-down experiments with 7-methyl GTP agarose. To analyze IR-induced cell death, dissipation of the mitochondrial membrane potential and DNA fragmentation were determined by flow cytometry. Protein levels of the different initiation factors were down-regulated using RNA interference approach.

Results

IR induced caspase-dependent cleavage of the translational initiation factors eIF4G1, eIF3A, and eIF4B resulting in disassembly of the cap-dependent initiation complex. In addition, DAP5-dependent initiation complex that regulates IRES-dependent translation was disassembled in response to IR. Moreover, IR resulted in dephosphorylation of 4EBP1, an inhibitor of cap-dependent translation upstream of caspase activation. However, knock-down of eIF4G1, eIF4B, DAP5, or 4EBP1 did not affect IR-induced decline of the anti-apoptotic protein Mcl-1.

Conclusion

Our data shows that cap-dependent translation is regulated at several levels in response to IR. However, the experiments indicate that IR-induced Mcl-1 decline is not a consequence of translational inhibition in Jurkat cells.
Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO
Authors: Zangrillo Alberto , Biondi-Zoccai Giuseppe , Landoni Giovanni , Frati Giacomo , Patroniti Nicolò , Pesenti Antonio , Pappalardo Federico
Published: February 2013

Introduction

H1N1 influenza can cause severe acute lung injury (ALI). Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial. We conducted a systematic review and meta-analysis on ECMO for H1N1-associated ALI.

Methods

CENTRAL, Google Scholar, MEDLINE/PubMed and Scopus (updated 2 January 2012) were systematically searched. Studies reporting on 10 or more patients with H1N1 infection treated with ECMO were included. Baseline, procedural, outcome and validity data were systematically appraised and pooled, when appropriate, with random-effect methods.

Results

From 1,196 initial citations, 8 studies were selected, including 1,357 patients with confirmed/suspected H1N1 infection requiring intensive care unit admission, 266 (20%) of whom were treated with ECMO. Patients had a median Sequential Organ Failure Assessment (SOFA) score of 9, and had received mechanical ventilation before ECMO implementation for a median of two days. ECMO was implanted before inter-hospital patient transfer in 72% of cases and in most patients (94%) the veno-venous configuration was used. ECMO was maintained for a median of 10 days. Outcomes were highly variable among the included studies, with in-hospital or short-term mortality ranging between 8% and 65%, mainly depending on baseline patient features. Random-effect pooled estimates suggested an overall in-hospital mortality of 28% (95% confidence interval 18% to 37%; I2 = 64%).

Conclusions

ECMO is feasible and effective in patients with ALI due to H1N1 infection. Despite this, prolonged support (more than one week) is required in most cases, and subjects with severe comorbidities or multiorgan failure remain at high risk of in-hospital death.
Learning and memory in Rhodnius prolixus: habituation and aversive operant conditioning of the proboscis extension response
Authors: Vinauger Clément , Lallement Hélène , Lazzari Claudio R.
Published: February 2013

It has been largely accepted that the cognitive abilities of disease vector insects may have drastic consequences on parasite transmission. However, despite the research effort that has been invested in the study of learning and memory in haematophagous insects, hitherto few conclusive results have been obtained. Adapting procedures largely validated in Drosophila, honeybees and butterflies, we demonstrate here that the proboscis extension response (PER) of the haematophagous insect Rhodnius prolixus can be modulated by non-associative (habituation) and associative (aversive conditioning) learning forms. Thermal stimuli were used as both unconditional stimulus (appetitive temperatures) and negative reinforcement (thermal shock). In the first part of this work, the PER was habituated and dishabituated to thermal stimuli, demonstrating the true central processing of information and discarding motor fatigue or sensory adaptation. Habituation was revealed to be modulated by the spatial context. In the second part, bugs that were submitted to aversive operant conditioning stopped responding with PER to thermal stimulation more quickly than by habituation. They were able to use their training experience when tested up to 72 h later. Our work constitutes the first demonstration of PER habituation and conditioning in a blood-sucking insect and provides reproducible experimental tools for the study of the mechanisms underlying learning and memory in disease vectors.
Searching the coding region for microRNA targets
Authors: Marín Ray M. , Šulc Miroslav , Vaníček Jiří
Published: February 2013

Finding microRNA targets in the coding region is difficult due to the overwhelming signal encoding the amino acid sequence. Here, we introduce an algorithm (called PACCMIT-CDS) that finds potential microRNA targets within coding sequences by searching for conserved motifs that are complementary to the microRNA seed region and also overrepresented in comparison with a background model preserving both codon usage and amino acid sequence. Precision and sensitivity of PACCMIT-CDS are evaluated using PAR-CLIP and proteomics data sets. Thanks to the properly constructed background, the new algorithm achieves a lower rate of false positives and better ranking of predictions than do currently available algorithms, which were designed to find microRNA targets within 3′ UTRs.
Expressed Humility in Organizations: Implications for Performance, Teams, and Leadership
Authors: Owens Bradley P. , Johnson Michael D. , Mitchell Terence R.
Published: February 2013

We draw on eight different lab and field samples to delineate the effects of expressed humility on several important organizational outcomes, including performance, satisfaction, learning goal orientation, engagement, and turnover. We first review several literatures to define the construct of expressed humility, discuss its implications in social interactions, and distinguish expressed humility from related constructs. Using five different samples, Study 1 develops and validates an observer-report measure of expressed humility. Study 2 examines the strength of expressed humility predictions of individual performance and contextual performance (i.e., quality of team member contribution) relative to conscientiousness, global self-efficacy, and general mental ability. This study also reveals that with regard to individual performance, expressed humility may compensate for lower general mental ability. Study 3 reports insights from a large field sample that examines the relationship between leader-expressed humility and employee retention as mediated by job satisfaction and employee engagement as mediated by team learning orientation. We conclude with recommendations for future research.
The Autonomy Paradox: The Implications of Mobile Email Devices for Knowledge Professionals
Authors: Mazmanian Melissa , Orlikowski Wanda J. , Yates JoAnne
Published: February 2013

Our research examines how knowledge professionals use mobile email devices to get their work done and the implications of such use for their autonomy to control the location, timing, and performance of work. We found that knowledge professionals using mobile email devices to manage their communication were enacting a norm of continual connectivity and accessibility that produced a number of contradictory outcomes. Although individual use of mobile email devices offered these professionals flexibility, peace of mind, and control over interactions in the short term, it also intensified collective expectations of their availability, escalating their engagement and thus reducing their ability to disconnect from work. Choosing to use their mobile email devices to work anywhere/anytime—actions they framed as evidence of their personal autonomy—the professionals were ending up using it everywhere/all the time, thus diminishing their autonomy in practice. This autonomy paradox reflected professionals’ ongoing navigation of the tension between their interests in personal autonomy on the one hand and their professional commitment to colleagues and clients on the other. We further found that this dynamic has important unintended consequences—reaffirming and challenging workers’ sense of themselves as autonomous and responsible professionals while also collectively shifting the norms of how work is and should be performed in the contemporary workplace.
Vancomycin Clearance in High-Volume Venovenous Hemofiltration
Authors: Paciullo Christopher A , Harned Kevin C , Davis George A , Connor Michael J , Winstead P Shane
Published: February 2013

OBJECTIVE

To report the pharmacokinetic and pharmacodynamic properties of vancomycin in 4 patients undergoing high-volume continuous venovenous hemofiltration (CVVH).

CASE SUMMARY

Data from 4 patients prescribed high-volume CVVH for acute renal failure treated with vancomycin were analyzed. Vancomycin plasma concentrations were measured 4 and 24 hours after the end of a 1-hour vancomycin infusion. The mean therapy fluid rate on initiation of vancomycin was 56.2 mL/kg/h (range 48.0–65.5). The mean loading dose of vancomycin was 18.3 mg/kg (range 14.7–19.7). Median vancomycin concentration 4 hours after the dose was 18.1 mg/L (range 13.1–30.0). At 24 hours after the dose, only 1 patient had a detectable vancomycin concentration (5.2 mg/L).

DISCUSSION

There was a large variability in the clearance of vancomycin in this patient population. Current strategies for dosing vancomycin may lead to subtherapeutic trough concentrations. Vancomycin dosing in this patient population should be based on a detailed assessment of the CVVH prescription, vancomycin concentrations, and clinical needs and response.

CONCLUSIONS

An initial vancomycin dose of 20–25 mg/kg with frequent monitoring and adjustment is recommended for patients receiving high-volume CVVH.
Taking Epistemology Seriously: ‘Truth, Reason and Justice’ Revisited
Authors: Nicolson Donald
Published: February 2013

Underlying orthodox evidence theory is a number of epistemological assumptions about the ability of reason to deliver true descriptions which accurately describe and correspond to the ‘real’ world. Drawing extensively on both traditional philosophical and contemporary, particularly postmodernist, scepticism this article provides a detailed critique of realist epistemological assumptions about reason, truth and knowledge. It argues that claims to reason, truth and knowledge can never escape the impact of individual perspective, community standards and power relations. At the same time, however, it rejects the realist assertion that subjectivism and relativism are oxymoronic or self-defeating positions. Instead, it is argued that epistemological scepticism is a healthy political position to adopt in that it guards against the complacent acceptance of seemingly authoritative assertions of reason, truth and knowledge.
Syntheses and applications of small metallic nanorods from solution and physical vapor deposition
Authors: Stagon Stephen P. , Huang Hanchen
Published: February 2013

Metallic nanorods have a wide range of important technological applications. Fabrication of metallic nanorods of ~100 nm using physical vapor deposition (PVD) has been commonplace for several decades. On this length scale, nanorods have similar functionalities to bulk thin films with the advantage of increased surface area. When the lateral dimension is decreased to ~10 nm new functionalities emerge that are not present in thin film counterparts, such as catalysis. Small metallic nanorods, those ~10 nm, have classically been made through solution-based synthesis. Alternatively, recent advances in scientific understanding, a framework of nanorod growth, have opened the door to the fabrication of small nanorods through PVD. Growing small nanorods through PVD offers technologically relevant advantages over solution-based processing like direct control of aspect ratio, pure high-vacuum processing, and oriented attachment to a substrate. Among materials, gold (Au) has a wide range of technological applications and is a good prototype for understanding the behavior of common face center cubic metals. This article reviews solution processing and PVD of small metallic nanorods using Au as a prototype, in terms of scientific understanding and fabrication knowledge, and further compares and contrasts the two approaches.
Shift in Kiss1 Cell Activity Requires Estrogen Receptor α
Authors: Frazão Renata , Cravo Roberta M. , Donato Jose , Ratra Dhirender V. , Clegg Deborah J. , Elmquist Joel K. , Zigman Jeffrey M. , Williams Kevin W. , Elias Carol F.
Published: February 2013

Reproductive function requires timely secretion of gonadotropin-releasing hormone, which is controlled by a complex excitatory/inhibitory network influenced by sex steroids. Kiss1 neurons are fundamental players in this network, but it is currently unclear whether different conditions of circulating sex steroids directly alter Kiss1 neuronal activity. Here, we show that Kiss1 neurons in the anteroventral periventricular and anterior periventricular nuclei (AVPV/PeN) of males and females exhibit a bimodal resting membrane potential (RMP) influenced by KATPchannels, suggesting the presence of two neuronal populations defined as type I (irregular firing patterns) and type II (quiescent). Kiss1 neurons in the arcuate nucleus (Arc) are also composed of firing and quiescent cells, but unlike AVPV/PeN neurons, the range of RMPs did not follow a bimodal distribution. Moreover, Kiss1 neuronal activity in the AVPV/PeN, but not in the Arc, is sexually dimorphic. In females, estradiol shifts the firing pattern of AVPV/PeN Kiss1 neurons and alters cell capacitance and spontaneous IPSCs amplitude of AVPV/PeN and Arc Kiss1 populations in an opposite manner. Notably, mice with selective deletion of estrogen receptor α (ERα) from Kiss1 neurons show cellular activity similar to that observed in ovariectomized females, suggesting that estradiol-induced changes in Kiss1 cellular properties require ERα. We also show that female prepubertal Kiss1 neurons are under higher inhibitory influence and all recorded AVPV/PeN Kiss1 neurons were spontaneously active. Collectively, our findings indicate that changes in cellular activity may underlie Kiss1 action in pubertal initiation and female reproduction.
Protracted Postnatal Development of Sparse, Specific Dentate Granule Cell Activation in the Mouse Hippocampus
Authors: Yu Esther P. , Dengler Christopher G. , Frausto Shanti F. , Putt Mary E. , Yue Cuiyong , Takano Hajime , Coulter Douglas A.
Published: February 2013

The dentate gyrus (DG) is a critical entry point regulating function of the hippocampus. Integral to this role are the sparse, selective activation characteristics of the principal cells of the DG, dentate granule cells (DGCs). This sparse activation is important both in cognitive processing and in regulation of pathological activity in disease states. Using a novel, combined dynamic imaging approach capable of resolving sequentially both synaptic potentials and action potential firing in large populations of DGCs, we characterized the postnatal development of firing properties of DG neurons in response to afferent activation in mouse hippocampal-entorhinal cortical slices. During postnatal development, there was a protracted, progressive sparsification of responses, accompanied by increased temporal precision of activation. Both of these phenomena were primarily mediated by changes in local circuit inhibition, and not by alterations in afferent innervation of DGCs because GABAAantagonists normalized developmental differences. There was significant θ and γ frequency-dependent synaptic recruitment of DGC activation in adult, but not developing, animals. Finally, we found that the decision to fire or not fire by individual DGCs was robust and repeatable at all stages of development. The protracted postnatal development of sparse, selective firing properties, increased temporal precision and frequency dependence of activation, and the fidelity with which the decision to fire is made are all fundamental circuit determinants of DGC excitation, critical in both normal and pathological function of the DG.
Caudate Nucleus in Retrieval of Trace Eyeblink Conditioning after Consolidation
Authors: Flores Luke C. , Disterhoft John F.
Published: February 2013

Trace eyeblink conditioning (EBC) is an associative learning task in which a stimulus-free trace period separates the presentation of a behaviorally neutral conditioned stimulus (CS; whisker stimulation) from a behaviorally salient unconditioned stimulus (US; air puff to the eye). Repeated pairings of the CS with the US results in the emergence of the conditioned response (CR; eyeblink after CS presentation and before US presentation). The goal of these experiments was to determine whether the caudate nucleus (CN) plays a role in retrieval of previously acquired trace EBC after memory consolidation. Lesions of the CN were made 1 month after initial trace EBC. CN-lesioned rabbits performed fewer adaptive CRs and more short-latency non-adaptive responses than sham-lesioned controls. They were not able to improve their CR performance after consolidation as were controls. Single-unit recordings taken from separate cohorts of rabbits demonstrated that neurons in the CN were still responsive to the CS and US 1 month after initial trace EBC, particularly in the medial and ventral CN on trials when a CR occurred. The proportion of rate-increasing neurons was higher in trace-conditioned than in pseudo-conditioned rabbits. Neurons in regions destroyed in the behavioral experiment demonstrated prolonged firing during the trace period, which might underlie the results from the behavioral experiment. These data demonstrate that the CN plays an important role in retrieval of a previously learned associative task after memory consolidation has occurred.
Fatty Acid Transport Protein 4 (FATP4) Prevents Light-Induced Degeneration of Cone and Rod Photoreceptors by Inhibiting RPE65 Isomerase
Authors: Li Songhua , Lee Jungsoo , Zhou Yongdong , Gordon William C. , Hill James M. , Bazan Nicolas G. , Miner Jeffrey H. , Jin Minghao
Published: February 2013

Although rhodopsin is essential for sensing light for vision, it also mediates light-induced apoptosis of photoreceptors in mouse. RPE65, which catalyzes isomerization of all-transretinyl fatty acid esters to 11-cis-retinol (11cROL) in the visual cycle, controls the rhodopsin regeneration rate and photoreceptor susceptibility to light-induced degeneration. Mutations inRPE65have been linked to blindness in affected children. Despite such importance, the mechanism that regulates RPE65 function remains unclear. Through unbiased expression screening of a bovine retinal pigment epithelium (RPE) cDNA library, we have identified elongation of very long-chain fatty acids-like 1 (ELOVL1) and fatty acid transport protein 4 (FATP4), which each have very long-chain fatty acid acyl-CoA synthetase (VLCFA-ACS) activity, as negative regulators of RPE65. We found that the VLCFA derivative lignoceroyl (C24:0)-CoA inhibited synthesis of 11cROL, whereas palmitoyl (C16:0)-CoA promoted synthesis of 11cROL. We further found that competition of FATP4 with RPE65 for the substrate of RPE65 was also involved in the mechanisms by which FATP4 inhibits synthesis of 11cROL. FATP4 was predominantly expressed in RPE, and the FATP4-deficient RPE showed significantly higher isomerase activity. Consistent with these results, the regeneration rate of 11-cis-retinaldehyde and the recovery rate for rod light sensitivity were faster in FATP4-deficient mice than wild-type mice. Moreover, FATP4-deficient mice displayed increased accumulation of the cytotoxic all-transretinaldehyde and hypersusceptibility to light-induced photoreceptor degeneration. Our findings demonstrate that ELOVL1, FATP4, and their products comprise the regulatory elements of RPE65 and play important roles in protecting photoreceptors from degeneration induced by light damage.
Human and Monkey Ventral Prefrontal Fibers Use the Same Organizational Principles to Reach Their Targets: Tracing versus Tractography
Authors: Jbabdi Saad , Lehman Julia F. , Haber Suzanne N. , Behrens Timothy E.
Published: February 2013

This article is a comparative study of white matter projections from ventral prefrontal cortex (vPFC) between human and macaque brains. We test whether the organizational rules that vPFC connections follow in macaques are preserved in humans. These rules concern the trajectories of some of the white matter projections from vPFC and how the position of regions in the vPFC dictate the trajectories of their projections in the white matter. To address this question, we present a novel approach that combines direct tracer measurements of entire white matter trajectories in macaque monkeys with diffusion MRI tractography of both macaques and humans. The approach allows us to provide explicit validation of diffusion tractography and transfer tractography strategies across species to test the extent to which inferences from macaques can be applied to human neuroanatomy. Apart from one exception, we found a remarkable overlap between the two techniques in the macaque. Furthermore, the organizational principles followed by vPFC tracts in macaques are preserved in humans.
Adenosine and Dopamine Receptors Coregulate Photoreceptor Coupling via Gap Junction Phosphorylation in Mouse Retina
Authors: Li Hongyan , Zhang Zhijing , Blackburn Michael R. , Wang Steven W. , Ribelayga Christophe P. , O'Brien John
Published: February 2013

Gap junctions in retinal photoreceptors suppress voltage noise and facilitate input of rod signals into the cone pathway during mesopic vision. These synapses are highly plastic and regulated by light and circadian clocks. Recent studies have revealed an important role for connexin36 (Cx36) phosphorylation by protein kinase A (PKA) in regulating cell–cell coupling. Dopamine is a light-adaptive signal in the retina, causing uncoupling of photoreceptors via D4 receptors (D4R), which inhibit adenylyl cyclase (AC) and reduce PKA activity. We hypothesized that adenosine, with its extracellular levels increasing in darkness, may serve as a dark signal to coregulate photoreceptor coupling through modulation of gap junction phosphorylation. Both D4R and A2a receptor (A2aR) mRNAs were present in photoreceptors, inner nuclear layer neurons, and ganglion cells in C57BL/6 mouse retina, and showed cyclic expression with partially overlapping rhythms. Pharmacologically activating A2aR or inhibiting D4R in light-adapted daytime retina increased photoreceptor coupling. Cx36 among photoreceptor terminals, representing predominantly rod–cone gap junctions but possibly including some rod–rod and cone–cone gap junctions, was phosphorylated in a PKA-dependent manner by the same treatments. Conversely, inhibiting A2aR or activating D4R in daytime dark-adapted retina decreased Cx36 phosphorylation with similar PKA dependence. A2a-deficient mouse retina showed defective regulation of photoreceptor gap junction phosphorylation, fairly regular dopamine release, and moderately downregulated expression of D4R and AC type 1 mRNA. We conclude that adenosine and dopamine coregulate photoreceptor coupling through opposite action on the PKA pathway and Cx36 phosphorylation. In addition, loss of the A2aR hampered D4R gene expression and function.
Recurrent Connectivity Can Account for the Dynamics of Disparity Processing in V1
Authors: Samonds Jason M. , Potetz Brian R. , Tyler Christopher W. , Lee Tai Sing
Published: February 2013

Disparity tuning measured in the primary visual cortex (V1) is described well by the disparity energy model, but not all aspects of disparity tuning are fully explained by the model. Such deviations from the disparity energy model provide us with insight into how network interactions may play a role in disparity processing and help to solve the stereo correspondence problem. Here, we propose a neuronal circuit model with recurrent connections that provides a simple account of the observed deviations. The model is based on recurrent connections inferred from neurophysiological observations on spike timing correlations, and is in good accord with existing data on disparity tuning dynamics. We further performed two additional experiments to test predictions of the model. First, we increased the size of stimuli to drive more neurons and provide a stronger recurrent input. Our model predicted sharper disparity tuning for larger stimuli. Second, we displayed anticorrelated stereograms, where dots of opposite luminance polarity are matched between the left- and right-eye images and result in inverted disparity tuning in the disparity energy model. In this case, our model predicted reduced sharpening and strength of inverted disparity tuning. For both experiments, the dynamics of disparity tuning observed from the neurophysiological recordings in macaque V1 matched model simulation predictions. Overall, the results of this study support the notion that, while the disparity energy model provides a primary account of disparity tuning in V1 neurons, neural disparity processing in V1 neurons is refined by recurrent interactions among elements in the neural circuit.
Replication Protein A Links Cell Cycle Progression and the Onset of Neurogenesis inDrosophilaOptic Lobe Development
Authors: Zhou Liya , Luo Hong
Published: February 2013

Stem cell self-renewal and differentiation must be carefully controlled during development and tissue homeostasis. In theDrosophilaoptic lobe, neuroepithelial cells first divide symmetrically to expand the stem cell population and then transform into asymmetrically dividing neuroblasts, which generate medulla neurons. The mechanisms underlying this cell fate transition are not well understood. Here, we show a crucial role of some cell cycle regulators in this transition. We find that loss of function in replication protein A (RPA), which consists of three highly conserved protein subunits and functions in DNA replication, leads to disintegration of the optic lobe neuroepithelium and premature differentiation of neuroepithelial cells into medulla neuroblasts. Clonal analyses ofRPAloss-of-function alleles indicate thatRPAis required to prevent neuroepithelial cells from differentiating into medulla neuroblasts. Inactivation of the core cell cycle regulators, including the G1/S regulatorsE2F1,Cyclin E,Cdk2, andPCNA, and the G2/M regulatorsCyclin A,Cyclin B, andCdk1, mimicRPAloss-of-function phenotypes, suggesting that cell cycle progression is required for both maintaining neuroepithelial cell identity and suppressing neuroblast formation. We further find thatRPAorE2F1inactivation in the neuroepithelial cells correlates with downregulation of Notch signaling activity, which appears to result from Numb mislocalization. Thus, we have shown that the transition from neuroepithelial cells to neuroblasts is directly regulated by cell cycle regulators and propose a model in which the inhibition of neuroepithelial cell cycle progression downregulates Notch signaling activity through Numb, which leads to the onset of neurogenesis.