bluuebunny/crossref_metadata_2025 huggingface dataset:
Tertiary excess of fibroblast growth factor 23 and hypophosphatemia following kidney transplantation
Authors: Seeherunvong Wacharee , Wolf Myles
Published: October 2010

Seeherunvong W, Wolf M. Tertiary excess of fibroblast growth factor 23 and hypophosphatemia following kidney transplantation. Pediatr Transplantation 2011: 15:37–46. © 2010 John Wiley & Sons A/S.

Abstract:  Hypophosphatemia caused by inappropriate urinary phosphate wasting is a frequent metabolic complication of the early period following kidney transplantation. Although previously considered to be caused by tertiary hyperparathyroidism, recent evidence suggests a primary role for persistently elevated circulating levels of the phosphorus‐regulating hormone, FGF23. In the setting of a healthy renal allograft, markedly increased FGF23 levels from the dialysis period induce renal phosphate wasting and inhibition of calcitriol production, which contribute to hypophosphatemia. While such tertiary FGF23 excess and resultant hypophosphatemia typically abates within the first few weeks to months post‐transplant, some recipients manifest persistent renal phosphate wasting. Furthermore, increased FGF23 levels have been associated with increased risk of kidney disease progression, cardiovascular disease, and death outside of the transplant setting. Whether tertiary FGF23 excess is associated with adverse transplant outcomes is unknown. In this article, we review the physiology of FGF23, summarize its relationship with hypophosphatemia after kidney transplantation, and speculate on its potential impact on long‐term outcomes of renal allograft recipients.
Non‐Selective and Time‐Dependent Behavioural Responses of Common Toads (Bufo bufo) to Predator Acoustic Cues
Authors: Llusia Diego , Márquez Rafael , Beltrán Juan F.
Published: October 2010

Acoustic predator recognition has rarely been studied in anurans, in spite of the fact that hearing is widespread in these animals and that it has been demonstrated to play an important role in both arthropods and other vertebrates. Using field playback experiments, we tested the hypothesis that adult common toads (Bufo bufo) are capable of recognizing natural vocalizations of a common predator, the Eurasian otter (Lutra lutra), and show antipredator responses. We found that toads exposed to both natural (two types of otter sounds) and synthetic stimuli [white noise (WN) and otter sound‐based amplitude modulated WN] increased time allocated to locomotion and escape behaviour. These responses were correlated with time elapsed from sunset to the onset of testing and were independent from the type of acoustic signal, toad features and other environmental factors monitored. We conclude thatB. bufohas not developed a selective recognition of predator vocalizations, suggesting that low‐frequency or seismic sounds associated with predator movements may provide anurans with better cues about an approaching risk. We propose that the time‐dependent response to acoustic stimuli of common toads represents a case of threat‐sensitivity and demonstrates that it can occur even when the response to the threat is not predator specific.
Effects of host starvation on the symbiotic dinoflagellates from the sea anemone Stichodactyla mertensii
Authors: Zhu BaoHua , Pan KeHou , Wang GuangCe
Published: October 2010

Many tropical cnidarians, including anemones and corals, contain symbiotic dinoflagellates known as zooxanthellae. Photosynthesis by symbiotic dinoflagellates benefits the animal host and the proficiency of host metabolism also plays an important role in the nutrient status of the photosynthetic dinoflagellates. We aimed to determine the responses of symbiotic dinoflagellates to host starvation. The ultrastructure and some physiological indicators of symbiotic dinoflagellates (Symbiodinium sp., zooxanthellae) were examined in starved sea anemones (Stichodactyla mertensii; 3‐, 45‐ and 280‐day starvation). The cell size of zooxanthellae was not affected by starving the host; however, the ultrastructure and other physiological indicators of the zooxanthellae were affected. The photochemical efficiency of symbiotic dinoflagellates from anemones after 280 days of starvation was significantly (P < 0.01) higher than that of symbiotic dinoflagellates from anemones after 3‐ and 45‐day starvation. The number of symbiotic dinoflagellates from anemones decreased with increasing starvation duration. Generally, the chlorophyll a and c content of symbiotic dinoflagellates decreased significantly with longer anemone starvation. The tentacles of 3‐day starved anemones contained the most zooxanthellae, some of which were dividing and still enclosed within one periplast, and some had split entirely within one host vacuole. Moreover, each cell from 3‐day starved anemone contained up to five or six more mitochondria than those from 45‐ to 280‐day starved anemones. More lipid granules appeared in the zooxanthellae from 45‐ to 280‐day starved anemones. Pyrenoids, lobed accumulation bodies and calcium oxalate crystals existed in the symbiotic dinoflagellates from anemones at different starvation stages, which suggested that their existence had no correlation with host starvation. These findings contribute to an improved mechanistic understanding of the symbiotic relationship between zooxanthellae and anemones.
Pattern of renal diseases observed in native renal biopsies in adults in a single centre in Pakistan
Authors: MUBARAK MUHAMMED , KAZI JAVED I , NAQVI RUBINA , AHMED EJAZ , AKHTER FAZAL , NAQVI SYED AA , RIZVI SYED AH
Published: October 2010

Aim:  In the absence of a national renal biopsy registry, there is a paucity of information on the pattern of renal disease observed in native renal biopsies in adults in Pakistan.

Methods:  A retrospective review of native renal biopsies performed in adult patients was undertaken at the Sindh Institute of Urology and Transplantation (SIUT) during the period from July 1995 to December 2008. Renal biopsies were studied by light, immunoflourescence and electron microscopy. The renal biopsy diagnoses were categorized into the following groups: glomerulopathies (GN), tubulointerstitial diseases (TID), renal vascular diseases (VD), and hereditary diseases (HD).

Results:  A total of 1793 adult patients were included in the study. GN was the commonest diagnosis representing 83.9% of all biopsies. Primary GN (PGN) accounted for 86.9% and secondary GN (SGN) for 13%. When PGN was further analyzed, focal segmental glomerulosclerosis (FSGS) was the leading histopathological diagnosis, found in 29% of PGN, followed by membranous GN (MGN), seen in 23.5% of cases. Among SGN, lupus nephritis (44.1%) was the commonest, followed by amyloidosis (42.1%) and diabetic nephropathy (8.1%). TID comprised 11.6% of all renal biopsy diagnoses. VD and HD were less frequent, found in 3.9% and 0.4%, respectively.

Conclusion:  The pattern of biopsied renal pathology is similar to that reported recently from other parts of the world with similar biopsy indications.
Predictors of psychiatric symptom scores in a sample of Turkish high school students
Authors: Güner‐Küçükkaya Perihan , Işık Işıl
Published: October 2010

Most mental health problems start in adolescence and early adulthood. According to the literature, one out of five children and adolescents suffers at least one mental health problem. In this cross‐sectional study, the distribution of psychiatric symptom scores among 728 Turkish high school students in grades 9, 10, and 11 was examined and associated with the students' gender, type of school, and grade level, as well as parental attitudes. The Brief Symptom Inventory and The Global Severity Index were used in this study. The latter is a global index of the former, and assesses indications of psychopathological disturbance. Girls score significantly higher than boys on all subscales of the Inventory, and specifically the Index. The highest Global Severity Index scores were obtained from the students who were attending vocational high schools, those who were in 11th grade, and those who indicated indifferent parental attitudes. This study revealed the need for a closer investigation of those students who are at severe risk of mental health problems.
An audit of platelet transfusion within the Wellington Cancer Centre
Authors: Buhrkuhl D. C. , Karlsson M. K. P. , Carter J. M.
Published: October 2010

Aim:  An audit of platelet transfusion was performed to assess adherence to local prophylactic policy and to assess if therapeutic transfusions were administered in line with international recommendations.

Methods:  A prospective audit of platelet transfusion therapy was conducted at the Wellington Cancer Centre in patients with hypoproliferative thrombocytopenia over a 3‐month period from 26 January 2008 to 30 April 2008. There were 398 episodes of evaluable clinical decision activity generated through either platelet counts <50 × 109/L or platelet transfusion events. Each episode was assessed and defined as either adhering to or breaching the local prophylactic platelet transfusion policy.

Results:  Thrombocytopenia and/or platelet transfusion occurred in 63 patients aged 16–84 years with either a haematological or solid organ malignancy. Decisions to withhold prophylactic platelet transfusion in thrombocytopenic patients adhered to policy for 99% of platelet counts <50 × 109/L. Where transfusions were administered, 77% were prophylactic and 23% were for therapeutic indications. Prophylactic transfusions adhered to policy for 72% of platelet counts <50 × 109/L. Adherence to prophylactic transfusion policy for febrile patients with a threshold of ≤15 × 109/L was 84%, compared to 63% for stable afebrile patients with a threshold of ≤10 × 109/L. Where policy was breached, in 80% of cases the platelet count had not reached the prophylactic transfusion threshold. Of the clinical decisions leading to therapeutic transfusions, 67% were deemed appropriate and predominantly a single adult therapeutic dose of platelets was administered. Where multiple doses of platelets were transfused, 86% of these transfusion events either breached policy or were deemed suboptimal management.

Conclusion:  The audit demonstrated a high rate of adherence to local transfusion policy. Where policy was breached, predominantly a transfusion had occurred prior to a platelet count reaching the pre‐defined trigger. The use of multiple dose platelet transfusions was almost never appropriate. Educating staff in the use of a stringent transfusion policy may lead to reductions in platelet product use.
Optimizing care for acute medical patients: the Australasian Medical Assessment Unit Survey
Authors: McNeill G. B. S. , Brand C. , Clark K. , Jenkins G. , Scott I. , Thompson C. , Jenkins P.
Published: October 2010

Aim:  To ascertain the design and operational characteristics of acute Medical Assessment Units (MAU) located within Australasian hospitals, and to compare these with formal standards promulgated by the Internal Medicine Society of Australia and New Zealand (IMSANZ).

Method:  Descriptive study based on responses to questionnaires mailed to clinical and nursing leads of MAU in March 2009 with follow‐up reminders over 3 months. Hospitals that had an MAU that met predefined criteria were identified from an IMSANZ directory of sites based on recent contact with IMSANZ members and health department personnel and interrogation of hospital websites and attendance lists at recent MAU workshops.

Results:  Questionnaires were returned from 32 of 50 hospitals (response rate 64%). Most MAU (15/22; 68%) were less than 2 years old. MAU were smaller than recommended by IMSANZ. Sixty‐eight per cent were located over a 5‐min walk from the emergency department (ED). Delay in transfer of patients from the ED to the MAU was common. The medical service to the majority of MAU was provided by General Medicine physicians and cover was reduced at weekends. In the majority of MAU the emphasis on function was facilitating discharge of patients rather than managing patients with high acuity of illness.

Conclusions:  Our survey suggests that despite some variation in staffing and procedures, MAU seem to be well established and a promising means of decreasing ED access block. Future comparative study is required to evaluate further the effect of MAU on ED access block and ED length of stay.
Ethnicity and socioeconomic status predict initial continuous positive airway pressure compliance in New Zealand adults with obstructive sleep apnoea
Authors: Campbell A. , Neill A. , Lory R.
Published: October 2010

Background:  Understanding factors that contribute to low continuous positive airway pressure (CPAP) compliance will lead to improvements in the long‐term outcome of patients with obstructive sleep apnoea (OSA) syndrome. Both cultural and socioeconomic factors are likely to be important but have not been systematically studied.

Aim:  To examine the effect of ethnicity and socioeconomic status on initial CPAP usage for people with OSA in New Zealand.

Methods:  We retrospectively collected demographic, clinical and CPAP treatment‐related data on patients undergoing a 1‐month CPAP trial for a 10‐month period. We compared objectively measured CPAP usage (by anova) with self‐identified ethnicity; levels of socioeconomic deprivation (NZDep06 index), Epworth Sleepiness Scale (ESS) and Apnoea‐Hypopnoea Index (AHI).

Results:  A total of 214 patients with a mean age of 52.7 (±11.8) years, mean AHI 57.3 (±35.8) events per hour and mean ESS 13 (±5.58)/24 made up the cohort. CPAP usage which averaged 5.13 ± 2.34 h per night was significantly lower in patients of non‐European ethnicity (P = 0.019 univariate) and remained significant after socioeconomic status was added to the model (P = 0.048). Patients living in the most socioeconomically deprived areas showed significantly lower compliance with CPAP on univariate analysis (P = 0.024, NZDep06 scores 1&2, average 5.3 per night compared to score NZDep06 scores 9&10, average 4.3 h per night), but this effect was no longer significant once ethnicity was added to the model (P = 0.28).

Conclusion:  CPAP usage in New Zealand is affected by both ethnicity and level of socioeconomic deprivation. We recommend further research to unravel specific cultural and socioeconomic reasons for the variance reported.
An invasive management strategy is associated with improved outcomes in high‐risk acute coronary syndromes in patients with chronic kidney disease
Authors: Medi C. , Chew D. P. B. , Amerena J. , Coverdale S. , Soman A. , Astley C. , Rankin J. , Brieger D.
Published: October 2010

Introduction:  Chronic kidney disease (CKD) is associated with poor outcomes after acute coronary syndromes, yet selection for invasive investigation and management is low.

Methods:  Patients presenting with ST segment elevation myocardial infarction (STEMI) or intermediate‐ to high‐risk non‐ST segment elevation acute coronary syndrome (NSTEACS) (n = 2597) were stratified into groups based on kidney function, defined as normal (glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2), moderate CKD (GFR 30–59 mL/min/1.73 m2) and severe CKD (GFR <30 mL/min/1.73 m2). Based on these stratums of kidney function, incidence and outcome measures were obtained for: rates of angiography and revascularization; 6‐month mortality; and the incidence and outcome of in‐hospital acute kidney impairment (AKI).

Results:  Patients with CKD were less likely to be offered coronary angiography after STEMI/NSTEACS (P < 0.001); however, after selection, revascularization rates were similar (percutaneous coronary intervention (P = 0.8); surgery (P = 0.4)). Six‐month mortality rates increased with CKD (GFR ≥ 60, 2.8%; GFR 30–59, 9.9%; GFR < 30, 16.5%, P ≤ 0.001), as well as the combined efficacy/safety end‐point (GFR ≥ 60, 9.4%; GFR 30–59, 20.2%; GFR < 30, 27.1%, P ≤ 0.001). Six‐month mortality was lower in patients who had received prior angiography (GFR ≥ 60, 1.5% vs 3.6%, P = 0.001; GFR 30–59, 5.1% vs 12.7%, P < 0.001; GFR < 30, 7.3% vs 18.5%, P = 0.094). Risk of AKI increased with CKD (GFR ≥ 60, 0.7%; GFR 30–59, 3.4%; GFR < 30, 6.8%, P ≤ 0.001), and was associated with high 6‐month mortality (35.6% vs 4.1%, P < 0.001).

Conclusions:  In patients with CKD after STEMI/NSTEACS, 6‐month mortality and morbidity is high, selection for angiography is lower, yet angiography is associated with a reduced long‐term mortality, and with comparable revascularization rates to those without CKD. In‐hospital AKI is more common in CKD and predicts a high 6‐month mortality.
Parasitism, predation and the evolution of animal personalities
Authors: Kortet Raine , Hedrick Ann V. , Vainikka Anssi
Published: October 2010

Ecology Letters(2010) 13: 1449–1458

Trade‐offs between behavioural traits promoting high life‐history productivity and mortality may fuel the evolution of animal personalities. We propose that parasites, including pathogens, impose fitness costs comparable to those from predators, and influence the adaptiveness of personality traits associated with productivity (PAPs). Whether personality traits are adaptive or not may also depend on individual immunological capacity. We illustrate this using a conceptual example in which the optimal level of PAPs depends on predation, parasitism and host compensation (resistance and tolerance) of parasitism’s negative effects. We assert that inherent differences in host immune function can produce positive feedback loops between resource intake and compensation of parasitism’s costs, thereby providing variation underlying the evolution of stable personalities. Our approach acknowledges the condition dependence of immune function and co‐evolutionary dynamics between hosts and parasites.
Recombinant protein production in a variety of Nicotiana hosts: a comparative analysis
Authors: Conley Andrew J. , Zhu Hong , Le Linda C. , Jevnikar Anthony M. , Lee Byong H. , Brandle Jim E. , Menassa Rima
Published: October 2010

Although many different crop species have been used to produce a wide range of vaccines, antibodies, biopharmaceuticals and industrial enzymes, tobacco has the most established history for the production of recombinant proteins. To further improve the heterologous protein yield of tobacco platforms, transient and stable expression of four recombinant proteins (i.e. human erythropoietin and interleukin‐10, an antibody against Pseudomonas aeruginosa, and a hyperthermostable α‐amylase) was evaluated in numerous species and cultivars of Nicotiana. Whereas the transient level of recombinant protein accumulation varied significantly amongst the different Nicotiana plant hosts, the variety of Nicotiana had little practical impact on the recombinant protein concentration in stable transgenic plants. In addition, this study examined the growth rate, amount of leaf biomass, total soluble protein levels and the alkaloid content of the various Nicotiana varieties to establish the best plant platform for commercial production of recombinant proteins. Of the 52 Nicotiana varieties evaluated, Nicotiana tabacum (cv. I 64) produced the highest transient concentrations of recombinant proteins, in addition to producing a large amount of biomass and a relatively low quantity of alkaloids, probably making it the most effective plant host for recombinant protein production.
The role of transgenic crops in sustainable development
Authors: Raymond Park Julian , McFarlane Ian , Hartley Phipps Richard , Ceddia Graziano
Published: October 2010

The concept of sustainable development forms the basis for a wide variety of international and national policy making. World population continues to expand at about 80 M people per year, while the demand for natural resources continues to escalate. Important policies, treaties and goals underpin the notion of sustainable development. In this paper, we discuss and evaluate a range of scientific literature pertaining to the use of transgenic crops in meeting sustainable development goals. It is concluded that a considerable body of evidence has accrued since the first commercial growing of transgenic crops, which suggests that they can contribute in all three traditional pillars of sustainability, i.e. economically, environmentally and socially. Management of herbicide‐tolerant and insect‐resistant transgenic crops to minimize the risk of weeds and pests developing resistance is discussed, together with the associated concern about the risk of loss of biodiversity. As the world population continues to rise, the evidence reviewed here suggests it would be unwise to ignore transgenic crops as one of the tools that can help meet aspirations for increasingly sustainable global development.
Regulation of amino acid/carnitine transporter B0,+(ATB0,+) in astrocytes by protein kinase C: independent effects on raft and non‐raft transporter subpopulations
Authors: Samluk Łukasz , Czeredys Magdalena , Nałęcz Katarzyna A.
Published: October 2010

J. Neurochem.(2010)115,1386–1397.

Neutral and basic amino acid transporter B0,+belongs to a Na,Cl‐dependent superfamily of proteins transporting neurotransmitters, amino acids and osmolytes, known to be regulated by protein kinase C (PKC). The present study demonstrates an increased phosphorylation of B0,+on serine moiety after treatment of rat astrocytes with phorbol 12‐myristate 13‐acetate, a process correlated with an augmented activity ofl‐leucine transport and an enhanced presence of the transporter at the cell surface. After solubilization with Triton X‐100 and sucrose gradient centrifugation, B0,+was detected in non‐raft as well as in detergent‐resistant raft fractions under control conditions, while phorbol 12‐myristate 13‐acetate treatment resulted in a complete disappearance of the transporter from the raft fraction. B0,+was observed to interact with caveolin‐1 and flotillin‐1 (reggie‐2) proteins, the markers of detergent‐resistant microdomains of plasma membrane. As verified in immunocytochemistry and immunoprecipitation experiments, modification of PKC activity did not affect these interactions. It is proposed that PKC reveals different effects on raft and non‐raft subpopulations of B0,+. Phorbol ester treatment results in trafficking of the transporter from the intracellular pool to non‐raft microdomains and increased activity, while B0,+present in raft microdomains undergoes either internalization or is transferred laterally to non‐raft domains.
GAD65 is essential for synthesis of GABA destined for tonic inhibition regulating epileptiform activity
Authors: Walls Anne B. , Nilsen Linn Hege , Eyjolfsson Elvar M. , Vestergaard Henrik T. , Hansen Suzanne L. , Schousboe Arne , Sonnewald Ursula , Waagepetersen Helle S.
Published: October 2010

J. Neurochem. (2010) 115, 1398–1408.

GABA is synthesized from glutamate by glutamate decarboxylase (GAD), which exists in two isoforms, that is, GAD65 and GAD67. In line with GAD65 being located in the GABAergic synapse, several studies have demonstrated that this isoform is important during sustained synaptic transmission. In contrast, the functional significance of GAD65 in the maintenance of GABA destined for extrasynaptic tonic inhibition is less well studied. Using GAD65−/− and wild type GAD65+/+ mice, this was examined employing the cortical wedge preparation, a model suitable for investigating extrasynaptic GABAA receptor activity. An impaired tonic inhibition in GAD65−/− mice was revealed demonstrating a significant role of GAD65 in the synthesis of GABA acting extrasynaptically. The correlation between an altered tonic inhibition and metabolic events as well as the functional and metabolic role of GABA synthesized by GAD65 was further investigated in vivo. Tonic inhibition and the demand for biosynthesis of GABA were augmented by injection of kainate into GAD65−/− and GAD65+/+ mice. Moreover, [1‐13C]glucose and [1,2‐13C]acetate were administered to study neuronal and astrocytic metabolism concomitantly. Subsequently, cortical and hippocampal extracts were analyzed by NMR spectroscopy and mass spectrometry, respectively. Although seizure activity was induced by kainate, neuronal hypometabolism was observed in GAD65+/+ mice. In contrast, kainate evoked hypermetabolism in GAD65−/− mice exhibiting deficiencies in tonic inhibition. These findings underline the importance of GAD65 for synthesis of GABA destined for extrasynaptic tonic inhibition, regulating epileptiform activity.
Cellular organization of adult neurogenesis in the Common Marmoset
Authors: Bunk Eva C. , Stelzer Sandra , Hermann Sven , Schäfers Michael , Schlatt Stefan , Schwamborn Jens C.
Published: October 2010

Adult neurogenesis within the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricle (LV) has been most intensely studied within the brains of rodents such as mice and rats. However, little is known about the cell types and processes involved in adult neurogenesis within primates such as the common marmoset (Callithrix jacchus). Moreover, substantial differences seem to exist between the neurogenic niche of the LV between rodents and humans. Here, we set out to use immunohistochemical and autogradiographic analysis to characterize the anatomy of the neurogenic niches and the expression of cell type–specific markers in those niches in the adult common marmoset brain. Moreover, we demonstrate significant differences in the activity of neurogenesis in the adult marmoset brain compared to the adult mouse brain. Finally, we provide evidence for ongoing proliferation of neuroblasts within both the SGZ and SVZ of the adult brain and further show that the age‐dependent decline of neurogenesis in the hippocampus is associated with a decrease in neuroblast cells.
Pyruvate imbalance mediates metabolic reprogramming and mimics lifespan extension by dietary restriction in Caenorhabditis elegans
Authors: Mouchiroud Laurent , Molin Laurent , Kasturi Prasad , Triba Mohamed N. , Dumas Marc Emmanuel , Wilson Marieangela C. , Halestrap Andrew P. , Roussel Damien , Masse Ingrid , Dallière Nicolas , Ségalat Laurent , Billaud Marc , Solari Florence
Published: October 2010

Dietary restriction (DR) is the most universal intervention known to extend animal lifespan. DR also prevents tumor development in mammals, and this effect requires the tumor suppressor PTEN. However, the metabolic and cellular processes that underly the beneficial effects of DR are poorly understood. We identified slcf‐1 in an RNAi screen for genes that extend Caenorhabditis elegans lifespan in a PTEN/daf‐18‐dependent manner. We showed that slcf‐1 mutation, which increases average lifespan by 40%, mimics DR in worms fed ad libitum. An NMR‐based metabolomic characterization of slcf‐1 mutants revealed lower lipid levels compared to wild‐type animals, as expected for dietary‐restricted animals, but also higher pyruvate content. Epistasis experiments and metabolic measurements support a model in which the long lifespan of slcf‐1 mutants relies on increased mitochondrial pyruvate metabolism coupled to an adaptive response to oxidative stress. This response requires DAF‐18/PTEN and the previously identified DR effectors PHA‐4/FOXA, HSF‐1/HSF1, SIR‐2.1/SIRT‐1, and AMPK/AAK‐2. Overall, our data show that pyruvate homeostasis plays a central role in lifespan control in C. elegans and that the beneficial effects of DR results from a hormetic mechanism involving the mitochondria. Analysis of the SLCF‐1 protein sequence predicts that slcf‐1 encodes a plasma membrane transporter belonging to the conserved monocarboxylate transporter family. These findings suggest that inhibition of this transporter homolog in mammals might also promote a DR response.
Spinal or systemic TY005, a peptidic opioid agonist/neurokinin 1 antagonist, attenuates pain with reduced tolerance
Authors: Largent‐Milnes TM , Yamamoto T , Nair P , Moulton JW , Hruby VJ , Lai J , Porreca F , Vanderah TW
Published: October 2010

BACKGROUND AND PURPOSEThe use of opioids in treating pain is limited due to significant side effects including somnolence, constipation, analgesic tolerance, addiction and respiratory depression. Pre‐clinical studies have shown that neurokinin 1 (NK1) receptor antagonists block opioid‐induced antinociceptive tolerance and may inhibit opioid‐induced rewarding behaviours. Here, we have characterized a bifunctional peptide with both opioid agonist and NK1antagonist pharmacophores in a rodent model of neuropathic pain.

EXPERIMENTAL APPROACHRats were evaluated for behavioural responses to both tactile and thermal stimuli in either an uninjured, sham‐ or nerve‐injured state. TY005 (Tyr‐DAla‐Gly‐Phe‐Met‐Pro‐Leu‐Trp‐O‐3,5‐Bn(CF3)2) was delivered spinally or systemically to assess the antinociceptive effects after acute exposure. Motor skills were evaluated using the rotarod test to determine potential sedative effects. Spinal TY005 was given chronically to sham‐ or nerve‐injured animals to determine the development of tolerance.

KEY RESULTSBolus injections of TY005 produced dose‐dependent antinociception in non‐injured animals and alleviated nerve injury‐induced thermal and tactile hypersensitivities (i.e. antihyperalgesia) more effectively than morphine. Sedative effects were not evident from the rotarod test at doses that were antihyperalgesic, nor at doses threefold higher. Repeated administration of TY005 did not lead to the development of antihyperalgesic tolerance or alter sensory thresholds.

CONCLUSIONS AND IMPLICATIONSCollectively, the data suggest that opioid agonist/NK1antagonist bifunctional peptides represent a promising novel approach to the management of chronic pain without the development of tolerance, reducing the need for escalation of doses and unwanted side effects associated with opiates alone.
Critical care: does profusion of evidence lead to confusion in practice?*
Authors: McKenna Hugh
Published: October 2010

There have been a plethora of articles on evidence‐based practice or its many derivative terms (evidence‐based nursing, evidence‐based medicine, evidence‐based health care, etc.). However, the word ‘based’ implies an almost unquestioning belief in evidence. I will argue that the term ‘Evidence Informed Practice’ is probably more accurate. This argument will be underpinned by Archie Cochrane's ‘road to Damascus' questioning of the value of soft over hard interventions and challenge what is held up as gold‐standard evidence. The differences in definitions of evidence‐based practice will also be discussed. Carper's identification of ethical, aesthetic and personal knowing will be used to debunk the myth that empirical evidence is always the gold standard for care and treatment. It will be argued that empirical evidence can be ignored when it clashes with other types of evidence. Finally, the tension between certainty and agreement with evidence will be explored.
An evaluation of enteral feeding practices in critically ill children
Authors: Tume Lyvonne , Latten Lynne , Darbyshire Andy
Published: October 2010

Background: Establishing and sustaining enteral feeding in critically ill children is challenging and has met with many problems.

Aims and objectives: The aim of this study was to investigate (a) how actual calorie intake compared with estimated caloric requirements and (b) whether feeding guideline adherence resulted in improved nutritional intake.

Design and methods: A prospective observational study was undertaken over 1 month in a tertiary referral paediatric intensive care unit (PICU) in the northwest of England.

Results: Forty‐seven children were studied, with a wide range of diagnoses in a 1‐month period. Only 47% of the children had enteral feeds started within our 6 h post‐admission target. Over half (55%) of the children received less than half of their estimated calorie requirements, but if feeding guidelines were followed, this resulted in a significantly higher (p = 0·004) delivery of the child's estimated requirements.

Conclusions: This study found that many children are not receiving adequate nutrition in PICU and that the use of feeding guidelines significantly improves calorie delivery in PICU patients.

Relevance to clinical practice: This paper highlights the dearth of research related to enteral feeding in critically ill children. We found that the use of feeding guidelines improved calorie delivery and so units should be encouraged to develop their own guidelines based on the best evidence available.
Progress in linking accessory mineral growth and breakdown to major mineral evolution in metamorphic rocks: a thermodynamic approach in the Na2O‐CaO‐K2O‐FeO‐MgO‐Al2O3‐SiO2‐H2O‐TiO2‐ZrO2 system
Authors: KELSEY D. E. , POWELL R.
Published: October 2010

Activity‐composition (a–x) models have been generated for zirconium‐bearing haplogranitic silicate melt and garnet from experimental data on zircon dissolution and natural rock data, respectively. Additionally including the recently proposed a–x model for Zr‐bearing rutile [Tomkins et al., Journal of Metamorphic Geology25 (2007) 401], calculated phase diagrams that explicitly include ZrO2 in the bulk composition predict the growth and dissolution of zircon at sub‐ and supra‐solidus conditions. This occurs within the context of the evolution of major metamorphic minerals and mineral assemblages in pressure‐temperature‐composition space for a metapelitic rock composition. The stability of zircon is a function of the bulk ZrO2 content. Garnet contains insufficient Zr to affect the stability of zircon whereas rutile does contain sufficient Zr that zircon stability can be curtailed in rocks with significant rutile. Silicate melt contains appreciable Zr and zircon abundance varies inversely with melt abundance. Thermometers based on the Zr‐content of rutile (and potentially garnet) can be graphically portrayed as compositional contours in mineral assemblage fields on the phase diagrams, thereby potentially adding to the utilization of such thermometers. The ability to calculate phase diagrams explicitly including Zr is a major step towards more systematically linking zircon growth – and zircon geochronology – and accessory phase thermometry in a readily adaptable way to the metamorphic evolution of major silicate minerals in a wide range of rocks.
Origin of felsic granulite microstructure by heterogeneous decomposition of alkali feldspar and extreme weakening of orogenic lower crust during the Variscan orogeny
Authors: FRANĚK J. , SCHULMANN K. , LEXA O. , ULRICH S. , ŠTÍPSKÁ P. , HALODA J. , TÝCOVÁ P.
Published: October 2010

This study answers the question of origin and evolution of a granulitic microstructure typically developed in felsic granulites of the European Variscan belt. It shows that the precursor of the Variscan felsic granulites was a high‐pressure alkali feldspar‐rich coarse‐grained layered orthogneiss. Its S1 subhorizontal layering is defined by the alignment of alkali feldspar porphyroclasts alternating with monomineralic bands of quartz and bands rich in plagioclase and garnet. The alkali feldspar porphyroclasts contain inclusions of quartz, garnet, kyanite, biotite and rutile, reflecting peak P–T conditions of 1.6–1.8 GPa and 850 °C during S1 formation. Superimposed steep folds and steep cleavage, S2, are associated with recrystallization of alkali feldspar, plagioclase and quartz, and garnet chemistry modifications that correspond to 0.9–1.0 GPa and 800 °C. During exhumation, involving 0.8 GPa decompression and cooling, the probably perthitic alkali feldspar underwent an unusual process of heterogeneous decomposition along irregular reaction fronts forming a fine‐grained matrix composed of plagioclase and K‐feldspar grains. Regular grain distributions in the matrix, nucleation‐dominated crystal size distribution and preservation of lattice orientation of the parental perthite crystals are all explained by a discontinuous precipitation process. This heterogeneous decomposition of alkali feldspar solid solution is controlled by chemically and strain induced grain‐boundary migration. During exhumation and decompression, the fine‐grained matrix underwent viscous deformation, forming the typical microstructure of the Variscan granulites. Random phase distributions, minor coarsening and feldspar textures are interpreted as a result of strain softening due to diffusion creep‐accommodated grain‐boundary sliding. Subordinate large quartz ribbons were rheologically stronger than the feldspar‐dominated matrix due to the activity of different deformational mechanisms. Finally, in mid‐crustal levels, the subvertical structure was overprinted by a perpendicular steep fabric associated with the growth of sillimanite, heterogeneous hydration and local partial melting, development of aggregate phase distributions and significant coarsening. This evolution is accompanied with the development of a strong lattice preferred orientation of quartz, K‐feldspar and plagioclase, reflecting a switch to dislocation creep mechanism and a general hardening of the granulites under amphibolite facies conditions.
Greenhouse Gas Emissions and Operational Electricity Use in the ICT and Entertainment & Media Sectors
Authors: Malmodin Jens , Moberg Åsa , Lundén Dag , Finnveden Göran , Lövehagen Nina
Published: October 2010

The positive and negative environmental impacts of information and communication technology (ICT) are widely debated. This study assesses the electricity use and greenhouse gas (GHG) emissions related to the ICT and entertainment & media (E&M) sectors at sector level, including end users, and thus complements information on the product level. GHGs are studied in a life cycle perspective, but for electricity use, only the operational use is considered. The study also considers which product groups or processes are major contributors. Using available data and extrapolating existing figures to the global scale for 2007 reveals that the ICT sector produced 1.3% of global GHG emissions in 2007 and the E&M sector 1.7%. The corresponding figures for global electricity use were 3.9% and 3.2%, respectively. The results indicate that for the ICT sector, operation leads to more GHG emissions than manufacture, although impacts from the manufacture of some products are significant. For the E&M sector, operation of TVs and production of printed media are the main reasons for overall GHG emissions. TVs as well as printed media, with the estimations made here, led to more GHG emissions on a global level in 2007 than PCs (manufacture and operation). A sector study of this type provides information on a macro scale, a perspective easily lost when considering, for example, the product‐related results of life cycle assessments. The macro scale is essential to capture changes in total consumption and use. However, the potential of the ICT sector to help decrease environmental impacts from other sectors was not included in the assessment.
Industrial Ecology 2.0
Authors: Davis Chris , Nikolic Igor , Dijkema Gerard P.J.
Published: October 2010

Industrial ecology (IE) is an ambitious field of study where we seek to understand systems using a wide perspective ranging from the scale of molecules to that of the planet. Achieving such a holistic view is challenging and requires collecting, processing, curating, and sharing immense amounts of data and knowledge.

We are not capable of fully achieving this due to the current state of tools used in IE and current community practices. Although we deal with a vastly interconnected world, we are not so good at efficiently interconnecting what we learn about it. This is not a problem unique to IE, and other fields have begun to use tools supported by the World Wide Web to meet these challenges.

We discuss these sets of tools and illustrate how community driven data collection, processing, curation, and sharing is allowing people to achieve more than ever before. In particular, we discuss standards that have been created to allow for interlinking of data dispersed across multiple Web sites. This is currently visible in the Linking Open Data initiative, which among others contains interlinked datasets from the U.S. and U.K. governments, biology databases, and Wikipedia. Since the types of technologies and standards involved are outside the normal scope of work by many industrial ecologists, we attempt to explain the relevance, implications, and benefits through a discussion of many real examples currently on the Web.

From these, we discuss several best practices, which can be enabling factors for how IE and the community can more efficiently and effectively meet its ambitions—an agenda for Industrial Ecology 2.0.
Greater Three‐Dimensional Ventricular Lead Tip Separation is Associated with Improved Outcome after Cardiac Resynchronization Therapy
Authors: ARIGA RINA , TAYEBJEE MUZAHIR H. , BENFIELD ANNE , TODD MICHELLE , LEFROY DAVID C.
Published: October 2010

Background: Effective cardiac resynchronization therapy (CRT) is more likely with widely separated left ventricular (LV) and right ventricular (RV) pacing leads tips. We hypothesized that lead separation is an important factor in determining the clinical response to CRT.

Methods: A retrospective study of 86 consecutive patients age 71 ± 10 years, male (74%), coronary disease (71%), atrial fibrillation (23%), LV ejection fraction (22 ± 9%), QRS duration (160 ± 27 ms), New York Heart Association (NYHA) class III (81%), NYHA class IV (19%) undergoing CRT from January 2006 to September 2008. The median follow‐up was 12 months and clinical response to CRT was defined as reduction of NYHA class by one or more. The three‐dimensional separation between RV and LV pacing lead tips was calculated using measurements obtained from orthogonal posteroanterior and lateral chest radiographs performed the day after implantation.

Results: Fifty‐nine patients (69%) responded to CRT. There was a statistically significant association between increased three‐dimensional lead separation and clinical response to CRT (P= 0.005). Stronger association was obtained when lead separation was corrected for cardiac size (P= 0.001). A significantly higher response rate of 88% was achieved in patients with QRS duration of 160 ms or more, and lead separation of 100 mm or more compared with 60% when lead separation was less than 100 mm and QRS duration remained the same (P = 0.027).

Conclusions: Greater three‐dimensional separation of LV‐to‐RV leads is associated with improved response to CRT. A prospective multicenter trial is needed to assess lead separation as a predictor for response. (PACE 2010; 33:1490–1496)
Elective Coronary Stenting Increases Fractional Flow Reserve in Other Arteries due to an Increase in Microvascular Resistance: Clinical Implications for Assessment of Multivessel Disease
Authors: HOOLE STEPHEN P. , HECK PATRICK M. , EPSTEIN ANDREW C. , CLARKE SARAH C. , WEST NICK E. J. , DUTKA DAVID P.
Published: October 2010

Introduction: Fractional flow reserve (FFR) can guide percutaneous coronary intervention (PCI) in multivessel disease (MVD). However, the effect of target vessel (TV) stenting on subsequent FFR measurements in remote non‐TVs (NTVs) is unknown. We investigated the effect of TV stenting on NTV FFR in patients with MVD.

Methods:
 Patients with MVD (>50% stenosis, ≥2 vessels >2.5 mm diameter; n = 51) undergoing elective PCI were studied. NTV distal pressure, aortic pressure, and saline‐bolus thermodilution transit time (Tmn) were measured at baseline and during maximal hyperemia to derive FFR, index of myocardial resistance (IMR), and coronary flow reserve (CFR). PCI was then performed to the TV and the measurements repeated. Collaterals were assessed by modified Rentrop score before and after TV stenting.

Results:
 Mean FFR increased in the NTV after stenting the TV (0.79 ± 0.02 vs. 0.81 ± 0.02; P < 0.01), particularly in patients with normal baseline IMR (0.77 ± 0.02 vs. 0.80 ± 0.02; P = 0.001; n = 41). In this group, PCI to the TV increased remote microvascular resistance (NTV IMR increased from 12.5 ± 0.7 to 16.3 ± 1.4; P = 0.007; and CFR decreased from 3.0 ± 0.2 to 2.4 ± 0.2; P = 0.008). This change was independent of angiographic loss of coronary collaterals from the NTV.

Conclusion:
 Elective TV PCI increases NTV FFR due to an increase in remote coronary microvascular resistance in patients with normal microvascular function. The effect of stent deployment on subsequent FFR measurements in other arteries should be considered. (J Interven Cardiol 2010;23:520–527)
Benefits of larval group feeding by Chrysolina aurichalcea asclepiadis on Vincetoxicum: improved host location or feeding facilitation?
Authors: Weed Aaron S.
Published: October 2010

Several studies have shown that group feeding by immature insects enhances larval performance through feeding facilitation. However, the benefits of this behavior have not been studied for species that hatch off from their host plant. For these taxa, group feeding may enhance recruitment of newly emerging larvae and may improve larval performance through feeding facilitation. I conducted laboratory experiments with the European chrysomelid Chrysolina aurichalcea asclepiadis (Villa) (Coleoptera: Chrysomelidae: Chrysomelinae), whose larvae hatch on the ground near their host plant [Vincetoxicum (Apocynaceae)] and feed in groups during early instars, to determine whether cues associated with larval feeding enhance neonate establishment and determine whether feeding in groups improves larval performance. Neonates located shoots infested with larvae more often than when confined to shoots with leaves that were undamaged or mechanically damaged. When provided a choice, neonates preferred shoots infested with 10 larvae to non‐infested shoots and shoots with one or five larvae. In the larval performance test, group feeding did not improve survival, but larvae completed larval development about 2 days faster when larvae were raised in groups of 10 compared to isolated larvae. However, larval group size negatively affected the size of emerging adults. The results of this study indicate that the main benefit of group feeding is to young C. a. asclepiadis larvae and this benefit diminishes over development due to competition of mature larvae.
Phronêsis vs Scepticism: An Early Modernist Perspective
Authors: Cervantes Fernando
Published: October 2010

Taking advantage of the way in which Charles Taylor hinges his account of the rise of modern secularity around the year 1500, this article attempts a reassessment of some aspects of early modern thought which have been prominent in recent studies. In particular, it focuses on the thin boundary between illusion and reality, on the lure of scepticism, and on the changing role of the Aristotelian notion of phronêsis in human action.
A Secular Age: an exercise in breach-mending
Authors: Flanagan Kieran
Published: October 2010

This article considers three aspects of Taylor's A Secular Age: the issue of the status and authority of theological insights derived from sociological analyses; the irresolvable ambiguities of secularity, where it marks the disappearance of religion but inadvertently affirms its persistence; and the properties of nostalgia and memory that unexpectedly shape post-secularity and the forms of enchantment it seeks.
Being Post-secular in the Social Sciences: Taylor's Social Imaginaries
Authors: Lyon David
Published: October 2010

Following the fall of mainstream secularization paradigms, this article suggests opportunities arise for considering social and political life as ‘religious’ phenomena and, specifically, for using Taylor's pregnant notion of ‘social imaginaries’ as a bridge between ‘secular’ and ‘post-secular’ social science. Thus, themes implicit in A Secular Age are made explicit and used to challenge how social science is done in ‘post-secular’ times.
Multiculturalism, Catholicism and Us
Authors: Tester Keith
Published: October 2010

Taylor addresses A Secular Age to an ‘us’ identified with the West. In this way the book is particularised and entered into a conversation. It is a prime example of the multiculturalism Taylor acclaims. However the paper argues that the commitment to multiculturalism forces A Secular Age to downplay the importance of Catholicism as an institution. It is contended that the book is a great work of catholicity (small ‘c’) but in need of more Catholicism (capital ‘C’).