bluuebunny/crossref_metadata_2025 huggingface dataset:
The energy required to produce materials: constraints on energy-intensity improvements, parameters of demand
Authors: Gutowski Timothy G. , Sahni Sahil , Allwood Julian M. , Ashby Michael F. , Worrell Ernst
Published: January 2013

In this paper, we review the energy requirements to make materials on a global scale by focusing on the five construction materials that dominate energy used in material production: steel, cement, paper, plastics and aluminium. We then estimate the possibility of reducing absolute material production energy by half, while doubling production from the present to 2050. The goal therefore is a 75 per cent reduction in energy intensity. Four technology-based strategies are investigated, regardless of cost: (i) widespread application of best available technology (BAT), (ii) BAT to cutting-edge technologies, (iii) aggressive recycling and finally, and (iv) significant improvements in recycling technologies. Taken together, these aggressive strategies could produce impressive gains, of the order of a 50–56 per cent reduction in energy intensity, but this is still short of our goal of a 75 per cent reduction. Ultimately, we face fundamental thermodynamic as well as practical constraints on our ability to improve the energy intensity of material production. A strategy to reduce demand by providing material services with less material (called ‘material efficiency’) is outlined as an approach to solving this dilemma.
Material efficiency: providing material services with less material production
Authors: Allwood Julian M. , Ashby Michael F. , Gutowski Timothy G. , Worrell Ernst
Published: January 2013

Material efficiency, as discussed in this Meeting Issue, entails the pursuit of the technical strategies, business models, consumer preferences and policy instruments that would lead to a substantial reduction in the production of high-volume energy-intensive materials required to deliver human well-being. This paper, which introduces a Discussion Meeting Issue on the topic of material efficiency, aims to give an overview of current thinking on the topic, spanning environmental, engineering, economics, sociology and policy issues. The motivations for material efficiency include reducing energy demand, reducing the emissions and other environmental impacts of industry, and increasing national resource security. There are many technical strategies that might bring it about, and these could mainly be implemented today if preferred by customers or producers. However, current economic structures favour the substitution of material for labour, and consumer preferences for material consumption appear to continue even beyond the point at which increased consumption provides any increase in well-being. Therefore, policy will be required to stimulate material efficiency. A theoretically ideal policy measure, such as a carbon price, would internalize the externality of emissions associated with material production, and thus motivate change directly. However, implementation of such a measure has proved elusive, and instead the adjustment of existing government purchasing policies or existing regulations— for instance to do with building design, planning or vehicle standards—is likely to have a more immediate effect.
A one-dimensional platinum mixed-valence complex with bridging thiocyanate S atoms: [[PtII(en)2](μ-SCN)[PtIV(en)2](μ-SCN)](ClO4)4(en is ethane-1,2-diamine)
Authors: Ozawa Yoshiki , Kim Misa , Toriumi Koshiro
Published: January 2013

A new one-dimensional platinum mixed-valence complex with nonhalogen bridging ligands, namelycatena-poly[[[bis(ethane-1,2-diamine-κ2N,N′)platinum(II)]-μ-thiocyanato-κ2S:S-[bis(ethane-1,2-diamine-κ2N,N′)platinum(IV)]-μ-thiocyanato-κ2S:S] tetrakis(perchlorate)], {[Pt2(SCN)2(C2H8N2)4](ClO4)4}n, has been isolated. The PtIIand PtIVatoms are located on centres of inversion and are stacked alternately, linked by the S atoms of the thiocyanate ligands, forming an infinite one-dimensional chain. The PtIV—S and PtII...S distances are 2.3933 (10) and 3.4705 (10) Å, respectively, and the PtIV—S...PtIIangle is 171.97 (4)°. The introduction of nonhalogen atoms as bridging ligands in this complex extends the chemical modifications possible for controlling the amplitude of the charge-density wave (CDW) state in one-dimensional mixed-valence complexes. The structure of a discrete PtIVthiocyanate compound, bis(ethane-1,2-diamine-κ2N,N′)bis(thiocyanato-κS)platinum(IV) bis(perchlorate) 1.5-hydrate, [Pt(SCN)2(C4H8N2)2](ClO4)2·1.5H2O, has monoclinic (C2) symmetry. TwoS-bound thiocyanate ligands are located intranspositions, with an S—Pt—S angle of 177.56 (3)°.
Laboratory seismic monitoring of supercritical CO2 flooding in sandstone cores using the Split Hopkinson Resonant Bar technique with concurrent x‐ray Computed Tomography imaging
Authors: Nakagawa Seiji , Kneafsey Timothy J. , Daley Thomas M. , Freifeld Barry M. , Rees Emily V.
Published: January 2013

Accurate estimation of CO2 saturation in a saline aquifer is essential for the monitoring of supercritical CO2 injected for geological sequestration. Because of strong contrasts in density and elastic properties between brine and CO2 at reservoir conditions, seismic methods are among the most commonly employed techniques for this purpose. However the relationship between seismic (P‐wave) velocity and CO2 saturation is not unique because the velocity depends on both wave frequency and the CO2 distribution in rock. In the laboratory, we conducted measurements of seismic properties of sandstones during supercritical CO2 injection. Seismic responses of small sandstone cores were measured at frequencies near 1 kHz, using a modified resonant bar technique (Split Hopkinson Resonant Bar method). Concurrently, saturation and distribution of supercritical CO2 in the rock cores were determined via x‐ray CT scans. Changes in the determined velocities generally agreed with the Gassmann model. However, both the velocity and attenuation of the extension wave (Young's modulus or ‘bar’ wave) for the same CO2 saturation exhibited differences between the CO2 injection test and the subsequent brine re‐injection test, which was consistent with the differences in the CO2 distribution within the cores. Also, a comparison to ultrasonic velocity measurements on a bedded reservoir rock sample revealed that both compressional and shear velocities (and moduli) were strongly dispersive when the rock was saturated with brine. Further, large decreases in the velocities of saturated samples indicated strong sensitivity of the rock's frame stiffness to pore fluid.
Niche differentiation of ammonia oxidizers and nitrite oxidizers in rice paddy soil
Authors: Ke Xiubin , Angel Roey , Lu Yahai , Conrad Ralf
Published: January 2013

The dynamics of populations and activities of ammonia‐oxidizing and nitrite‐oxidizing microorganisms were investigated in rice microcosms treated with two levels of nitrogen. Different soil compartments (surface, bulk, rhizospheric soil) and roots (young and old roots) were collected at three time points (the panicle initiation, heading and maturity periods) of the season. The population dynamics of bacterial (AOB) and archaeal (AOA) ammonia oxidizers was assayed by determining the abundance (using qPCR) and composition (using T‐RFLP and cloning/sequencing) of their amoA genes (coding for a subunit of ammonia monooxygenase), that of nitrite oxidizers (NOB) by quantifying the nxrA gene (coding for a subunit of nitrite oxidase of Nitrobacter spp.) and the 16S rRNA gene of Nitrospira spp. The activity of the nitrifiers was determined by measuring the rates of potential ammonia oxidation and nitrite oxidation and by quantifying the copy numbers of amoA and nxrA transcripts. Potential nitrite oxidation activity was much higher than potential ammonia oxidation activity and was not directly affected by nitrogen amendment demonstrating the importance of ammonia oxidizers as pace makers for nitrite oxidizer populations. Marked differences in the distribution of bacterial and archaeal ammonia oxidizers, and of Nitrobacter‐like and Nitrospira‐like nitrite oxidizers were found in the different compartments of planted paddy soil indicating niche differentiation. In bulk soil, ammonia‐oxidizing bacteria (Nitrosospira and Nitrosomonas) were at low abundance and displayed no activity, but in surface soil their activity and abundance was high. Nitrite oxidation in surface soil was dominated by Nitrospira spp. By contrast, ammonia‐oxidizing Thaumarchaeota and Nitrobacter spp. seemed to dominate nitrification in rhizospheric soil and on rice roots. In contrast to soil compartment, the level of N fertilization and the time point of sampling had only little effect on the abundance, composition and activity of the nitrifying communities. The results of our study show that in rice fields population dynamics and activity of nitrifiers is mainly differentiated by the soil compartments rather than by nitrogen amendment or season.
Demanding a safer tomorrow: Japan's anti‐nuclear rallies in the summer of 2012 (Respond to this article at http://www.therai.org.uk/at/debate)
Authors: Ogawa Akihiro
Published: January 2013

This article discusses Japan's nuclear energy policy and describes the anti‐nuclear protest demonstrations that were held in Japan throughout the summer of 2012, including the author's personal experiences at some of these protests, illuminating the grassroots nature of the current anti‐nuclear movement.
Citations out of place (Respond to this article at http://www.therai.org.uk/at/debate)
Authors: Fardon Richard
Published: January 2013

Mary Douglas wrote that she derived the phrase ‘dirt is matter out of place’ from Lord Chesterfield, but the authorship of something close to this phrase was more likely Lord Palmerston's, and it arose in the context of policy concerns over urban sewage and rural fertilizer. The phrase was picked up immediately, made more abstract, and applied in a variety of contexts that drew together moral judgements with considerations of hygiene. Hence the phrase had a complex authorship and usage that had already prepared it for the uses to which Douglas would put it, and its history shows how the aphoristic formulation of a widely held notion can provoke thought by, in twenty‐first century terms, going viral.
Effect of parasitoids, seed‐predators and ant‐mutualists on fruiting success and germination of Acacia drepanolobium in Kenya
Authors: Martins Dino J.
Published: January 2013

Acacia drepanolobium is an obligate ant‐plant that bears dehiscent pods exploited by predispersal seed‐predators and parasitoids. Fruit set and seed germination in relation to ant‐association, bruchid and parasitoid infestation were investigated in a large‐scale multi‐year study in Kenya. Ant‐association had a significant impact on the overall numbers of fruiting trees. 94.8% of Crematogaster mimosae‐occupied trees, 25.6% of C. nigriceps‐occupied trees, and 82.2% of Tetraponera penzigi‐occupied trees set fruit. Within each tree, ant‐association had no significant impact on the amount of seed produced: C. mimosae‐occupied trees produced 47.5 seeds per branch, C. nigriceps‐occupied trees 44.9 seeds per branch and T. penzigi‐occupied trees 38.3 seeds per branch. Ant‐association did not limit seed‐predators or vary significantly by ant. Seeds infested by bruchids germinated in significantly lower proportions (6.2%) compared to uninfested seed (78.6%). Bruchid‐infested seed is also exploited by parasitoid wasps. Parasitoids appear to have a moderate but significant ‘rescue’ effect on bruchid‐infested seed with 18.4% of parasitoid‐infested seed germinating. Stable isotopes (δ15N) revealed the trophic structure of the seed‐associated insects, showing clearly that bruchids are seed predators and the parasitoid wasp Dinarmus magnus exploits the dominant Bruchidius sp.
Infrequent attention to dietary and physical activity behaviours in conversations in Swedish child health services
Authors: Bohman B , Eriksson M , Lind M , Ghaderi A , Forsberg L , Rasmussen F
Published: January 2013

Aim

To investigate conversations between nurses and parents in Swedish child health services and to assess to what extent attention is directed towards dietary and physical activity behaviours in children.

Methods

Twenty‐three nurses audio‐recorded one session each. Recordings were assessed and topics were classified according to predetermined categories.

Results

The three most frequent topics of conversation concerned physical examinations of the child (30% of session time), talking to the child to establish or maintain contact and interest (15%), and development of language skills (12%). Dietary habits came on fourth place (10%), and physical activity ranked 14 (4%).

Conclusion

Attention to dietary and physical activity behaviours in children is infrequent in Swedish child health services. Concern is raised about the efficacy of prevention efforts against childhood obesity.
Transforming the Line of Control: Bringing the “Homeland” Back In
Authors: Mohan Surinder
Published: January 2013

The majority of existing research on the Indo‐Pakistani conflict has shown that this conflict persists due to the confronting actors' long‐term incompatibility in goals and their use of realpolitik conceptions to resolve their core issue—Kashmir. While most of this research is focused on the dynamics of already established realpolitik scholarship, less is known about how it contributed to make this dyad exceedingly dangerous in the post–Cold War era. The present effort attempts to account for the “action‐reaction conundrum” by illuminating how the traditional realist practices are performing contrary to their security maximization objectives in the India‐Pakistan rivalry. In order to bring the two states out of their prolonged security dilemma, what is needed is a way forward through the transformation of the Line of Control on the basis of an approach that combines the Westphalian state and an alternative paradigm. This article concludes by discussing the steps required to move in this direction, that is, toward Indo‐Pakistani coexistence and a progressive future for South Asia more generally.
A phase I study of pulse high‐dose vorinostat (V) plus rituximab (R), ifosphamide, carboplatin, and etoposide (ICE) in patients with relapsed lymphoma
Authors: Budde Lihua E. , Zhang Michelle M. , Shustov Andrei R. , Pagel John M. , Gooley Ted A. , Oliveira George R. , Chen Tara L. , Knudsen Nancy L. , Roden Jennifer E. , Kammerer Britt E. , Frayo Shani L. , Warr Thomas A. , Boyd Thomas E. , Press Oliver W. , Gopal Ajay K.
Published: January 2013

Given the poor outcomes of relapsed aggressive lymphomas and preclinical data suggesting that ≥2·5 μmol/l concentrations of vorinostat synergize with both etoposide and platinums, we hypothesized that pulse high‐dose vorinostat could safely augment the anti‐tumour activity of (R)ICE [(rituximab), ifosphamide, carboplatin, etoposide] chemotherapy. We conducted a phase I dose escalation study using a schedule with oral vorinostat ranging from 400 mg/d to 700 mg bid for 5 d in combination with the standard (R)ICE regimen (days 3, 4 and 5). Twenty‐nine patients [median age 56 years, median 2 prior therapies, 14 chemoresistant (of 27 evaluable), 2 prior transplants] were enrolled and treated. The maximally tolerated vorinostat dose was defined as 500 mg twice daily × 5 d. Common dose limiting toxicities included infection (n = 2), hypokalaemia (n = 2), and transaminitis (n = 2). Grade 3 related gastrointestinal toxicity was seen in 9 patients. The median vorinostat concentration on day 3 was 4·5 μmol/l (range 4·2–6·0 μmol/l) and in vitro data confirmed the augmented antitumour and histone acetylation activity at these levels. Responses were observed in 19 of 27 evaluable patients (70%) including 8 complete response/unconfirmed complete response. High‐dose vorinostat can be delivered safely with (R)ICE, achieves potentially synergistic drug levels, and warrants further study, although adequate gastrointestinal prophylaxis is warranted.
Biological roles of cAMP: variations on a theme in the different kingdoms of life
Authors: Gancedo Juana M.
Published: January 2013

Cyclic AMP (cAMP) plays a key regulatory role in most types of cells; however, the pathways controlled by cAMP may present important differences between organisms and between tissues within a specific organism. Changes in cAMP levels are caused by multiple triggers, most affecting adenylyl cyclases, the enzymes that synthesize cAMP. Adenylyl cyclases form a large and diverse family including soluble forms and others with one or more transmembrane domains. Regulatory mechanisms for the soluble adenylyl cyclases involve either interaction with diverse proteins, as happens in Escherichia coli or yeasts, or with calcium or bicarbonate ions, as occurs in mammalian cells. The transmembrane cyclases can be regulated by a variety of proteins, among which the α subunit and the βγ complex from G proteins coupled to membrane receptors are prominent. cAMP levels also are controlled by the activity of phosphodiesterases, enzymes that hydrolyze cAMP. Phosphodiesterases can be regulated by cAMP, cGMP or calcium‐calmodulin or by phosphorylation by different protein kinases. Regulation through cAMP depends on its binding to diverse proteins, its proximal targets, this in turn causing changes in a variety of distal targets. Specifically, binding of cAMP to regulatory subunits of cAMP‐dependent protein kinases (PKAs) affects the activity of substrates of PKA, binding to exchange proteins directly activated by cAMP (Epac) regulates small GTPases, binding to transcription factors such as the cAMP receptor protein (CRP) or the virulence factor regulator (Vfr) modifies the rate of transcription of certain genes, while cAMP binding to ion channels modulates their activity directly. Further studies on cAMP signalling will have important implications, not only for advancing fundamental knowledge but also for identifying targets for the development of new therapeutic agents.
The effect of mesenchymal stem cells on dynamic changes of T cell subsets in experimental autoimmune uveoretinitis
Authors: Li G , Yuan L , Ren X , Nian H , Zhang L , Han Z C , Li X , Zhang X
Published: January 2013

Mesenchymal stem cells (MSCs) are being explored extensively as a promising treatment for autoimmune diseases. We have recently reported that MSCs could ameliorate experimental autoimmune uveoretinitis (EAU) in rats. In this study, we examined further the effects of MSCs on the dynamics of T cell subsets in both eye and spleen and their cytokine production during the course of EAU. We focused on when and where the MSCs had inhibitory effects on T helper type 1 (Th1) and Th17 cells and how long the inhibitory effect lasted, in order to provide more mechanistic evidence for MSCs on the treatment of uveitis. Compared to the control group, administration of MSCs decreased the production of Th1 and Th17 cytokines significantly, while the production of Th2 and regulatory T cell (Treg) cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-β] was elevated during the entire course of EAU. Correspondingly, the dynamic levels of IL-17 in the aqueous humour (AqH) were reduced in MSC-treated rats. Moreover, the ratio of Th17/Treg cells in both spleen and eye was decreased. These results provide powerful evidence that MSCs can regulate negatively both Th1 and Th17 responses and restore the balance of Th17/Tregs in the whole course of EAU, which is important for the regression of the disease.
Up-regulation of alternate co-stimulatory molecules on proinflammatory CD28null T cells in bronchiolitis obliterans syndrome
Authors: Hodge G , Hodge S , Ahern J , Holmes-Liew C-L , Reynolds P N , Holmes M
Published: January 2013

Bronchiolitis obliterans syndrome (BOS) is associated with lack of immunosuppression of T cell proinflammatory cytokines and increased T cell granzyme B. Repeated antigen-driven proliferation down-regulates T cell CD28. We hypothesized that down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules (CD134, CD137, CD152 and CD154) on T cells may be associated with BOS. Co-stimulatory molecules, granzyme B, perforin and intracellular cytokines were measured by flow cytometry on T cells from stable lung transplant patients (n = 38), patients with BOS (n = 20) and healthy controls (n = 10). There was a significant increase in the percentage of CD4/28null and CD8/28null T cells producing granzyme B, interferon (IFN)-γ and tumour necrosis factor (TNF)-α in BOS compared with stable patients. Down-regulation of CD28 was associated with steroid resistance and up-regulation of CD134, CD137, CD152 and CD154 on CD4+ T cells and CD137 and CD152 on CD8+ T cells. There was a significant correlation between increased CD28null/CD137 T cells producing IFN-γ, TNF-α with BOS grade (r = 0·861, P < 0·001 for CD28null/CD137 IFN-γ/CD8) and time post-transplant (r = 0·698, P < 0·001 for CD28null/CD137 IFN-γ/CD8). BOS is associated with down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules on steroid-resistant peripheral blood proinflammatory CD4+ and CD8+ T cells. Therapeutic targeting of alternate co-stimulatory molecules on peripheral blood CD28null T cells and monitoring response using these assays may help in the management of patients with BOS.
Anxiety symptoms severity and short‐term clinical outcome in first‐episode psychosis
Authors: Montreuil Tina C. , Malla Ashok K. , Joober Ridha , Bélanger Claude , Lepage Martin
Published: January 2013

Aim

In psychotic disorders, a limited number of studies have documented the presence of symptoms of anxiety, especially in first‐episode psychosis (FEP). There is a growing interest in better understanding how these symptoms may affect the severity of psychotic symptoms and clinical outcome. This study examined the association between symptoms of anxiety, as measured by the Hamilton Anxiety Rating Scale (HARS) and the Positive and Negative Syndrome Scale (PANSS), and short‐term clinical outcome. We first examined the potential association between anxiety symptom severity among FEP patients and remission. A secondary objective explored the relation between the PANSS single item subscale ‘anxiety’ item and the total score value of the HARS.

Method

Data were collected on 201 FEP patients divided into remitted and unremitted groups based on clinical data at 6 months. Anxiety ratings were compared between 67 remitted and 99 unremitted patients with the HARS, and for 72 remitted and 103 unremitted patients with the (G2) PANSS.

Results

A significant interaction Time × Group was observed on the HARS and on the PANSS G2 item. Looking at the two time points specifically, groups did not significantly differ at baseline on either the HARS or the PANSS. At 6 months, these two groups were significantly different on both anxiety rating scores – HARS [t(170) = 3.48, P = 0.001)] and PANSS G2 [t(173) = 2.51, P = 0.013)].

Conclusion

Anxiety severity is marked in FEP, and appears to be linked to poor short‐term clinical outcome. The PANSS single item (G2) seems to represent a good indicator of anxiety as it significantly correlates with a more systematic measure of anxiety, namely the HARS score. Anxiety severity appears to vary across diagnosis type.
Transition to university: the role played by emotion
Authors: McMillan W.
Published: January 2013

Students experience transition to university as challenging. Recent studies implicate emotion in university success. This article reports on a pilot study to examine the extent to which school to university transition is experienced as emotional. Understanding the role of emotion in this transition can inform mechanisms for student support. This qualitative study used focus group interviews to elicit insider accounts of transition. The pilot cohort consisted of a tutorial group of twenty‐eight students from within the class of one hundred and eight‐first‐year students at one Faculty of Dentistry in South Africa. Three focus group interviews were conducted. Issues identified in the literature as significant were used to analyse the data. Eleven descriptive tags related to transition and associated with emotion were identified from the data. These were clustered into four themes – ‘academic challenges’, ‘friends and family’, ‘outside constraints’ and ‘identity’. Findings suggest that emotions are a natural part of the experience of transition. Drawing on insights of students' emotional needs, it is suggested that students in transition need a roadmap and a guide. A framework, to be used as a roadmap, is suggested. Peer mentoring is discussed as a mechanism for mediating the framework and thus for supporting students in the transition.
Pharmacodynamic and pharmacokinetic evaluation of coadministration of lacosamide and an oral contraceptive (levonorgestrel plus ethinylestradiol) in healthy female volunteers
Authors: Cawello Willi , Rosenkranz Bernd , Schmid Bernhard , Wierich Werner
Published: January 2013

Purpose

To determine whether the antiepileptic drug lacosamide affects the pharmacokinetics or pharmacodynamics of a combined oral contraceptive (OC; ethinylestradiol 0.03 mg plus levonorgestrel 0.15 mg).

Methods

This was an open‐label trial in healthy female volunteers. Eligible women entered cycle 1 of the trial on the first day of menstruation. Cycle 1 was a medication‐free, run‐in phase of approximately 28 days to confirm that normal ovulation occurred. Volunteers with confirmed ovulation entered the subsequent cycle and started taking OCs. After establishing ovulation suppression (defined as progesterone serum concentration <5.1 nm on day 21 of the menstrual cycle) in volunteers taking the OCs in cycle 2, lacosamide 400 mg/day was administered concomitantly in the subsequent cycle (cycle 3). The pharmacokinetic parameters of area under the concentration‐time curve (AUC), maximum steady‐state plasma drug concentration (Cmax), and time to maximum concentration (tmax) were measured for the OC components and lacosamide.

Key Findings

A total of 37 volunteers completed cycle 1, and 32 completed cycle 2. In each of the 31 volunteers who completed the trial (through cycle 3), pharmacodynamic assessment showed progesterone serum concentration was <5.1 nm on day 21 of cycle 2, when the OC was administered alone, and on day 21 of cycle 3, when lacosamide was administered concomitantly. The AUC of ethinylestradiol alone versus together with lacosamide was 1,067 ± 404 versus 1,173 ± 330 pg h/ml. Corresponding values of Cmax were 116.9 ± 48.8 versus 135.7 ± 28.6 pg/ml. For levonorgestrel, the AUC alone was 74.2 ± 21.4 versus 80.9 ± 18.5 ng h/ml with lacosamide. Corresponding values of Cmax were 6.7 ± 1.9 versus 7.4 ± 1.5 ng/ml. The AUC and Cmax point estimates and almost all 90% confidence intervals (except for Cmax of ethinylestradiol) for ethinylestradiol and levonorgestrel (with and without lacosamide) were within the conventional bioequivalence range, and no relevant changes in tmax were observed for ethinylestradiol (1.5 ± 0.6 h alone vs. 1.4 ± 0.7 h with lacosamide) or for levonorgestrel (1.5 ± 1.0 h alone vs. 1.1 ± 0.6 h with lacosamide). Lacosamide pharmacokinetics were consistent with those observed in previous studies of lacosamide alone, with values for AUC of 113.5 ± 20.7 μg h/ml, Cmax of 13.8 ± 2.2 μg/ml, and tmax of 1.1 ± 0.4 h.

Significance

Lacosamide and an OC containing ethinylestradiol and levonorgestrel have low potential for drug–drug interaction; therefore, coadministration of the two drugs is unlikely to result in contraceptive failure or loss of seizure control.
Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy
Authors: McCormick Cornelia , Quraan Maher , Cohn Melanie , Valiante Taufik A. , McAndrews Mary Pat
Published: January 2013

Purpose

The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change.

Methods

Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance–presurgical memory performance) data were available for half of these patients.

Key Findings

Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery.

Significance

Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE.
Sinus node dysfunction: An adverse effect of lacosamide
Authors: Chinnasami Suganthi , Rathore Chaturbhuj , Duncan John S.
Published: January 2013

Lacosamide, a recently introduced antiepileptic drug, acts by enhancing the slow inactivation of voltage‐dependent sodium channels. Cardiac conduction disturbances, namely atrial fibrillation and atrioventricular block, have been reported in patients with epilepsy. We report a patient with drug‐resistant focal epilepsy who developed asymptomatic sinus node dysfunction following lacosamide use, which resolved on stopping lacosamide. This is the first report of sinus node dysfunction associated with lacosamide therapy.
Hsp90, an unlikely ally in the war on cancer
Authors: Barrott Jared J. , Haystead Timothy A. J.
Published: January 2013

On the surface heat shock protein 90 (Hsp90) is an unlikely drug target for the treatment of any disease, let alone cancer. Hsp90 is highly conserved and ubiquitously expressed in all cells. There are two major isoforms α and β encoded by distinct genes and together they may constitute 1%–3% of the cellular protein. Deletion of the protein is embryonic lethal and there are no recognized polymorphisms suggesting an association or causal relationship with any human disease. With respect to cancer, the proteins absence from two recent high profile articles, ‘Hallmarks of cancer: the next generation’ [Hanahan & Weinberg (2011) Cell 144, 646–674] and ‘Comprehensive molecular portraits of human breast tumours’ [Koboldt et al. (2012) Nature] underlines the perception that it is an unlikely bona fide target to treat this disease. Yet, to date, there are 17 distinct Hsp90 inhibitors in clinical trials for multiple indications in cancer. The protein has been championed for over 20 years by the National Cancer Institute (Bethesda, MD, USA) as a cancer target since the discovery of the antitumor activity of the natural product geldanamycin. This review aims to look at the conundrum of why Hsp90 can even be considered a druggable target for the treatment of cancer. We propose that in contrast to the majority of chemotherapeutics our growing armamentarium of investigational Hsp90 drugs represents an elegant choice that offers real hope in the long‐term treatment of certain cancers.
Endoplasmic reticulum lectin XTP3‐B inhibits endoplasmic reticulum‐associated degradation of a misfolded α1‐antitrypsin variant
Authors: Fujimori Tsutomu , Kamiya Yukiko , Nagata Kazuhiro , Kato Koichi , Hosokawa Nobuko
Published: January 2013

The endoplasmic reticulum (ER) is an organelle that synthesizes many secretory and membrane proteins. However, proteins often fold incorrectly. Terminally misfolded polypeptides in the ER are retro‐translocated to the cytosol, where they are ultimately degraded by the ubiquitin–proteasome system, a process termed ER‐associated degradation (ERAD). By recognizing the specific structures of N‐linked oligosaccharides attached to polypeptides, lectins play an important role in the quality control of glycoproteins in the ER. Mammalian OS‐9 and XTP3‐B are ER‐resident lectins that contain mannose 6‐phosphate receptor homology (MRH) domains, which recognize sugar moieties; OS‐9 has one MRH domain and XTP3‐B has two. Both are involved in ERAD, but the functional differences between the two are poorly understood. The present study analyzed the function of human XTP3‐B, and found, by frontal affinity chromatography analysis, that its C‐terminal MRH domain specifically recognized the Man9GlcNAc2 (M9) glycan in vitro and M9 glycans on an ERAD substrate NHK, a terminally misfolded α1‐antitrypsin variant, in vivo. Furthermore, endogenous XTP3‐B was a component of the HRD1–SEL1L membrane‐embedded ubiquitin ligase complex, an association that was stabilized by a direct interaction with SEL1L. The lectin activity of XTP3‐B was required for its binding to NHK, but not for its association with SEL1L. Unlike OS‐9, XTP3‐B did not enhance the degradation of misfolded glycoproteins, but instead inhibited the degradation of NHK bearing M9 oligosaccharides. Therefore, we propose that XTP3‐B recognizes M9 glycans on unfolded polypeptides, thereby acting as a negative regulator of ERAD, and also protects newly synthesized immature polypeptides from premature degradation.
Effect of drying kinetics on main bioactive compounds and antioxidant activity of acerola (Malpighia emarginata D.C.) residue
Authors: Duzzioni Alexandra G. , Lenton Vanessa M. , Silva Diogo I. S. , Barrozo Marcos A. S.
Published: January 2013

This study investigates the drying kinetics of residue of acerola, in a fixed‐bed dryer, analysing the effect of the process variables on the antioxidant properties of the residue. A complete factorial design 32 has been performed, where the independent variables studied were as follows: air velocity (0.5, 1.0 and 1.5 m s−1) and air‐drying temperature (40, 50 and 60 °C). The bioactive compounds studied were L‐ascorbic acid, total phenolic, total flavonoids and antioxidant activity (expressed as IC50) was determined using free radical DPPH•. Both independent variables studied have shown to be statistically significant. The content of ascorbic acid was the highest at 60 °C and 1.0 m s−1 (126.2 ± 0.004 mg 100 g−1) while for the fresh residue 16.12 ± 0.003 mg 100 g−1, whereas the total phenolic showed the highest content at 50 °C and 1.5 m s−1 (46.2 ± 0.003 mg gallic acid.100 g−1) while for the fresh residue 12.59 ± 0.001 mg gallic acid.100 g−1. The drying conditions play an important role in determining the final quality of the product mainly in terms of antioxidant activity.
Tropical traditional fermented food, a field full of promise. Examples from the Tropical Bioresources and Biotechnology programme and other related French–Vietnamese programmes on fermented food
Authors: Lan Cao‐Hoang , Son Chu‐Ky , Ha Ho Phu , Florence Husson , Binh Le Thanh , Mai Le‐Thanh , Tram Nguyen Thi Hoai , Khanh Tran Thi Minh , Phu Tu Viet , Dominique Valentin , Yves Waché
Published: January 2013

In tropical countries, traditional fermented foods are usually home‐made products obtained through spontaneous fermentation or backslopping. They are now facing an evolution aiming at responding to quality, safety and mass production issues. This requires acquisition of knowledge on raw materials, microbial ecosystems and fermentation processes. Vietnam is a laboratory for such studies as traditional fermented foods play an important role in the diet of Vietnamese and as these foods are very diverse. Among the most popular are nem chua (sausage reminding Thai Nham), dua muoi (cabbage reminding Kimchi), tom chua (shrimps) and the well‐known nuoc mam. The challenge for these products to enter the industrial era is to reach a level of quality and safety without losing their character. Beside the research for starters to elaborate these products, the world of fermented products is also a world of innovation and the microbial ecosystem of traditional products can also be used for the adaptation of fermented products from other regions, such as wines (from grape or other fruits), for cross‐cultural innovations such as soy‐yogurts, for technology transfer from one fermentation (soy sauce) to another one (fish sauce) and for evolution of traditional products towards higher nutritional qualities such as nem chua nam (replacing part of the sausage meat by mushrooms). Finally, these complex microbial ecosystems are a source of probiotic, antimicrobial compounds and biocatalysts, which can benefit health and improve food processes worldwide. After a presentation of Vietnamese traditional fermented foods, this article aims at illustrating the diverse applications of research on fermented products through examples obtained in past research and in the Tropical Bioresources and Biotechnology project.
The basis examination of leukocyte–platelet aggregates with CD45 gating as a novel platelet activation marker
Authors: Nagasawa A. , Matsuno K. , Tamura S. , Hayasaka K. , Shimizu C. , Moriyama T.
Published: January 2013

Introduction

Platelet activation in circulation is considered to be associated with thrombosis and inflammation; thus, sensitive and easy‐to‐use markers are necessary. In this study, we established a simple and rapid protocol to clinically examine leukocyte–platelet aggregate formation associated with activated platelets in circulation.

Methods

Whole blood was stained with PC5‐conjugated anti‐CD45 monoclonal antibody and fluorescent isothiocyanate‐conjugated anti‐CD41 monoclonal antibody for leukocyte–platelet aggregate analysis. For platelet activation, 5 μm thrombin receptor–activated peptide (TRAP) or 2 μg/mL collagen was added. Samples were analyzed by EPICS XL (Beckman Coulter, Miami, FL, USA). Monocytes, neutrophils, and lymphocytes were gated based on differences in CD45 fluorescence intensity and side scatter. For each gate, the percentage (%) of platelets expressing CD41 was analyzed. Same drawing sample was stained with anti‐CD62P monoclonal antibody. Platelet CD62P expression was then analyzed with gating for platelet cell population.

Results

We analyzed leukocyte–platelet aggregates and platelet CD62P expression in 18 healthy individuals. Leukocyte–platelet aggregates, mainly monocyte–platelet aggregates, increased when platelets were activated by platelet agonists. Monocyte–platelet aggregates and neutrophil–platelet aggregates also increased over time with mild platelet activation.

Conclusion

Leukocyte–platelet aggregates, mainly monocyte–platelet aggregates, appear to be a sensitive marker of platelet activation in circulation.
The role of interferon‐β in the treatment of multiple sclerosis and experimental autoimmune encephalomyelitis – in the perspective of inflammasomes
Authors: Inoue Makoto , Shinohara Mari L.
Published: January 2013

Inflammasomes in innate immune cells mediate the induction of inflammation by sensing microbes and pathogen‐associated/damage‐associated molecular patterns. Inflammasomes are also known to be involved in the development of some human and animal autoimmune diseases. The Nod‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome is currently the most fully characterized inflammasome, although a limited number of studies have demonstrated its role in demyelinating autoimmune diseases in the central nervous system of humans and animals. Currently, the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), is known to be induced by the NLRP3 inflammasome through enhanced recruitment of inflammatory immune cells in the central nervous system. On the other hand, interferon‐β (IFNβ), a first‐line drug to treat MS, inhibits NLRP3 inflammasome activation, and ameliorates EAE. The NLRP3 inflammasome is indeed a factor capable of inducing EAE, but it is dispensable when EAE is induced by aggressive disease induction regimens. In such NLRP3 inflammasome‐independent EAE, IFN‐β treatment is generally not effective. This might therefore be one mechanism that leads to occasional failures of IFN‐β treatment in EAE, and possibly, in MS as well. In the current review, we discuss inflammasomes and autoimmunity; in particular, the impact of the NLRP3 inflammasome on MS/EAE, and on IFN‐β therapy.
Review paper: Instrumentation for marine magnetotelluric and controlled source electromagnetic sounding
Authors: Constable Steven
Published: January 2013

We review and describe the electromagnetic transmitters and receivers used to carry out magnetotelluric and controlled source soundings in the marine environment. Academic studies using marine electromagnetic methods started in the 1970s but during the last decade these methods have been used extensively by the offshore hydrocarbon exploration industry. The principal sensors (magnetometers and non‐polarizing electrodes) are similar to those used on land but magnetotelluric field strengths are not only much smaller on the deep sea‐floor but also fall off more rapidly with increasing frequency. As a result, magnetotelluric signals approach the noise floor of electric field and induction coil sensors (0.1 nV/m and 0.1 pT) at around 1 Hz in typical continental shelf environments. Fluxgate magnetometers have higher noise than induction coils at periods shorter than 500 s but can still be used to collect sea‐floor magnetotelluric data down to 40–100 s. Controlled source transmitters using electric dipoles can be towed continuously through the seawater or on the sea‐bed, achieving output currents of 1000 A or more, limited by the conductivity of seawater and the power that can be transmitted down the cables used to tow the devices behind a ship. The maximum source‐receiver separation achieved in controlled source soundings depends on both the transmitter dipole moment and on the receiver noise floor and is typically around 10 km in continental shelf exploration environments. The position of both receivers and transmitters needs to be navigated using either long baseline or short baseline acoustic ranging, while sea‐floor receivers need additional measurements of orientations from compasses and tiltmeters. All equipment has to be packaged to accommodate the high pressure (up to 40 MPa) and corrosive properties of seawater. Usually receiver instruments are self‐contained, battery powered and have highly accurate clocks for timekeeping, even when towed on the sea‐floor or in the water column behind a transmitter.
Diagnostic tests in urology: percutaneous biopsy of renal masses
Authors: Bell Michael D. , Lavallée Luke T. , Dahm Philipp , Witiuk Kelsey , Breau Rodney H.
Published: January 2013

What's known on the subject? and What does the study add?

Small renal masses are often detected incidentally with abdominal CT. About 80% of these masses are malignant. Many studies have investigated the diagnostic accuracy of small renal mass biopsy using various techniques. This has resulted in a broad range of published sensitivities and specificities without a clear guide for clinical use.

This evidence‐based medicine article addresses the clinical utility of renal mass biopsy. Based on a common patient scenario, a guide to calculating the probability of malignancy after a benign biopsy is provided. The scenario is used to show the potential influence of renal mass biopsy on clinical decision‐making. This appraisal also discusses the limitations of the current literature, highlighting the need for multi‐institutional studies with standardised biopsy techniques and a reliable comparator to confirm the clinical utility of this diagnostic test.
Extended pelvic lymphadenectomy and various radical prostatectomy techniques: is pelvic drainage necessary?
Authors: Danuser Hansjoerg , Di Pierro Giovanni Battista , Stucki Patrick , Mattei Agostino
Published: January 2013

What's known on the subject? and What does the study add?

The occurence of lymphoceles in patients after radical prostatectomy is well known (2–10%). It appears that patients undergoing open extraperitoneal radical prostatectomy develop more lymphoceles than patients undergoing robot‐assisted radical prostatectomy with transperitoneal access.

The present study investigates in a prospective randomized manner whether the time of drainage (1 vs 7 days) makes a difference or whether drainage is even necessary. The study data, collected in the same institution, are compared with the incidence of lymphocele in patients treated by robot‐assisted radical prostatectomy.

Objective

To investigate whether routine drainage is advisable after open extended pelvic lymph node dissection (ePLND) and retropubic radical prostatectomy (RRP) by measuring the incidence of lymphoceles and comparing these results with those of a series of robot‐assisted radical prostatectomy (RARP) and ePLND.

Patients and Methods

A total of 331 consecutive patients underwent ePLND and RRP or RARP.

The first 132 patients underwent open ePLND and RRP and received two pelvic drains; these patients were prospectively randomized into two groups: group 1 (n = 66), in which the drains were shortened on postoperative (PO) days 3 and 5 and removed on PO day 7, and group 2 (n = 66), in which the drains were removed on PO day 1.

The next 199 patients were assigned to two consecutive groups not receiving drainage: group 3 (n = 73) undergoing open ePLND and RRP, followed by group 4 (n = 126) treated by transperitoneal robot‐assisted ePLND and RARP.

All patients had ultrasonographic controls 5 and 10 days and 3 and 12 months after surgery.

Results

Lymphoceles were detected in 6.6% of all patients, 3.3% of whom were asymptomatic and 3.3% of whom were symptomatic.

Symptomatic lymphoceles were detected in 0% of group 1, 8% of group 2, 7% of group 3 and 1% of group 4, with groups 2 and 3 differing significantly from group 4 (P < 0.05).

In total, 5% of all patients undergoing open RRP (groups 1–3) had symptomatic lymphoceles vs 1% of patients undergoing RARP (group 4) (P = 0.06).

Nodal‐positive patients had significantly more symptomatic lymphoceles than nodal‐negative patients (10% vs 2%) (P < 0.02).

Conclusions

Symptomatic lymphoceles occur less frequently after open RRP and pelvic drainage over 7 days than after open RRP and pelvic drainage over 1 day or without drainage.

Patients undergoing RARP without drainage had significantly fewer lymphoceles than patients receiving open RRP without drainage.
The New England Research Institutes, Inc. (NERI) Nocturia Advisory Conference 2012: focus on outcomes of therapy
Authors: Weiss Jeffrey P. , Blaivas Jerry G. , Blanker Marco H. , Bliwise Donald L. , Dmochowski Roger R. , Drake Marcus , DuBeau Catherine E. , Hijaz Adonis , Rosen Raymond C. , Van Kerrebroeck Philip E.V. , Wein Alan J.
Published: January 2013

What's known on the subject? and What does the study add?

A consensus statement published in 2011 summarised current research, clinical approaches, and treatment options for nocturia. Since that time, new research has refined our understanding of nocturia in clinically important ways and new evidence has been presented on the efficacy and outcomes of several treatment methods for this underreported, infrequently recognised, and undertreated problem in adults. This paper provides updated guidance to clinicians in light of recent advances in the field.