bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing a standardized quality management system for the European Health Network GA2LEN*
Authors: Heinzerling L. , Burbach G. , Van Cauwenberge P. , Papageorgiou P. , Carlsen K.‐H. , Lødrup Carlsen K. C. , Zuberbier T.
Published: November 2009

To cite this article: Heinzerling L, Burbach G, van Cauwenberge P, Papageorgiou P, Carlsen K‐H, Lødrup Carlsen KC, Zuberbier T. Establishing a standardized quality management system for the European Health Network GA2LEN. Allergy 2010; 65: 743–752.

Background:  Quality management is increasingly important in clinical practice. The Global Allergy and Asthma European Network (GA2LEN) is a network of clinical and scientific excellence with originally 25 allergy centres in 16 European countries, a scientific society (European Academy of Allergology and Clinical Immunology), and a patient organization (European Federation of Allergy and Airways Diseases Patients’ Associations). Although some allergy centres adhere to internal quality criteria, the implementation of a standardized quality management system for allergy centres across Europe was lacking.

Objectives:  To implement standardized quality criteria among allergy centres organized within GA2LEN and thus ensure equal standards of diagnosis and care as well as to establish a culture of continuous quality improvement.

Methods:  Quality criteria covering, e.g., diagnostic and therapeutic procedures, and emergency preparedness to assure patient safety were developed and agreed upon by all 25 participating centres. To assure implementation of quality criteria, centres were audited to check quality indicators and document deviations. A follow‐up survey was used to assess the usefulness of the project.

Results:  Deviations were documented mainly in the areas of emergency care/patient safety (27.3% lacked regular emergency training of doctors and nurses; 22.7% inadequate emergency intervention equipment; 22.7% lacked critical incidence reporting/root cause analyses) and handling of extracts/pharmaceuticals (31.8% lacked temperature logs of fridges; 4.5% inadequate check of expiration dates). Quality improvement was initiated as shown by findings of re‐audits. Usefulness of the project was rated high.

Conclusion:  The establishment of a quality management system with joint standards of care and harmonized procedures can be achieved in an international health network and ensures quality of care.
The evolutionary consequence of the individualistic response to climate change
Authors: STEWART J. R.
Published: November 2009

The Quaternary fossil record has abundant evidence for ecologically nonanalogue communities made up of combinations of modern taxa not seen in sympatry today. A brief review of the literature detailing these nonanalogue communities is given with a discussion of their various proposed causes. The individualistic, Gleasonian, response of species to climate and environmental change is favoured by many. The degree to which communities are nonanalogue appears to increase with greater time depth, and this progressive process is a necessary outcome of the individualistic response of species to climate change through time. In addition, it is noted that populations within species, as well as the species as a whole, respond individualistically. This paper proposes that many elements of nonanalogue communities are extinct populations, which may explain their environmentally anomalous combinations. These extinct populations are, by definition, lineages without descendents. It is further proposed that the differential extinction of populations, as a result of continuous ecological reassembly, could amount to a significant evolutionary phenomenon.
Contrasting patterns of phenotypic variation linked to chromosomal inversions in native and colonizing populations of Drosophila subobscura
Authors: FRAGATA I. , BALANYÀ J. , REGO C. , MATOS M. , REZENDE E. L. , SANTOS M.
Published: November 2009

In fewer than two decades after invading the Americas, the fly Drosophila subobscura evolved latitudinal clines for chromosomal inversion frequencies and wing size that are parallel to the long‐standing ones in native Palearctic populations. By sharp contrast, wing shape clines also evolved in the New World, but the relationship with latitude was opposite to that in the Old World. Previous work has suggested that wing trait differences among individuals are partially due to the association between chromosomal inversions and particular alleles which influence the trait under consideration. Furthermore, it is well documented that a few number of effective individuals founded the New World populations, which might have modified the biometrical effect of inversions on quantitative traits. Here we evaluate the relative contribution of chromosomal inversion clines in shaping the parallel clines in wing size and contrasting clines in wing shape in native and colonizing populations of the species. Our results reveal that inversion‐size and inversion‐shape associations in native and colonizing (South America) populations are generally different, probably due to the bottleneck effect. Contingent, unpredictable evolution was suggested as an explanation for the different details involved in the otherwise parallel wing size clines between Old and New World populations of D. subobscura. We challenge this assertion and conclude that contrasting wing shape clines came out as a correlated response of inversion clines that might have been predicted considering the genetic background of colonizers.
Spatio‐temporal pattern ofPentastiridius leporinusmigration in an ephemeral cropping system
Authors: Bressan Alberto , Moral García Francisco J. , Sémétey Olivier , Boudon‐Padieu Elisabeth
Published: November 2009

Cixiid planthoppers (Hemiptera: Fulgoromorpha: Cixiidae) are considered to be important economic pests because of their ability to transmit phloem‐restricted prokaryotes causing emerging plant diseases worldwide. However, little information is available on the biology and ecology of such species. This is the case forPentastiridius leporinus(Linnaeus), a cixiid planthopper reported to live on common reed across Countries of Central and Northern Europe. However, in the east of France, the same planthopper species appears to complete its life cycle in the sugar beet‐wheat cropping system and has been repeatedly shown to transmit prokaryotic plant pathogens that are associated with an emerging disease of sugar beet called syndrome ‘basses richesses'.

To gather evidence on the biology of the planthopper in the cropping rotation, we analysed the flight activity of adults. We used transparent sticky traps for sampling migrating adults and quantified nymphs as well as emerging adults on the roots of wheat plants.

Results showed a significant correlation between disappearance of nymphs and emerging adults from wheat roots and the occurrence of migrant adults in nearby sugar beet fields. Planthoppers migrated more abundantly and colonized sugar beet for longer periods than any other crop available. Flight activity was very pronounced during the migratory phase that was extended from the middle of June to the middle of July. A geographic information system and geostatical analysis revealed that planthoppers flew and colonized the centre of the sugar beet field rather than the borders.

Overall, results obtained in the present study suggest that the ecology and biology of the planthopper vector in the cropping rotation is a primary factor that leads to the emergence of the syndrome ‘basses richesses' disease of sugar beet.
Impact of shade on the spatial distribution of Sahlbergella singularis in traditional cocoa agroforests
Authors: Babin Régis , Ten Hoopen Gerben M. , Cilas Christian , Enjalric Frank , Yede  , Gendre Pierre , Lumaret Jean‐Pierre
Published: November 2009

Shade management is commonly considered to be an effective pest management strategy for cocoa mirids, yet shade management recommendations are not based on extensive knowledge of the mirid ecology in traditional cocoa agroforests.

The main objectives of the present study were an assessment of the impact of shade on the spatial distribution of mirid populations and thus the evaluation of shade management strategies.

Mirid densities were measured and shade was characterized for three plots located in three different agroecological zones in the Centre region of Cameroon. Mirid densities generally followed a negative binomial law. Geostatistical procedures were used to characterize spatial distribution of mirid density. Light conditions were assessed using hemispherical photography.

Populations of Sahlbergella singularis were highly aggregated in the plots. Semivariance analysis and kriging visualized the spatial dependence of mirid densities. Clearly distinguishable mirid pockets of 20–30 adjacent infested cocoa trees were identified in two of the three plots.

The high diversity of shade tree species and the large variability in density and size of shade trees resulted in a considerable heterogeneity of plot light conditions. Percentage transmitted light varied in the range 9.4–80.1% in the most heterogeneous plot.

For two of the three plots, mirid pockets were aggregated in those areas where light transmission was highest. In the third plot, relatively high mirid densities and the presence of an alternative host resulted in a more homogeneous distribution. The importance of these findings for improved mirid control is discussed.
Radical prostatectomy findings in patients predicted to have low‐volume/low‐grade prostate cancer diagnosed by extended‐core biopsies: an analysis of volume and zonal distribution of tumour foci
Authors: Davis John W. , Kim Jeri , Ward John F. , Wang Xuemai , Nakanishi Hiro , Babaian R. Joseph , Troncoso Patricia
Published: November 2009

Study Type – Diagnosis (case series) Level of Evidence 4

OBJECTIVE

To measure total tumour volume (TTV) and dominant TV (DTV) in radical prostatectomy (RP) specimens from patients predicted to have low‐volume, low‐grade (LV/LG) prostate cancer, as this entity can be predicted from biopsy findings and prostate‐specific antigen (PSA) level, but tumour under‐sampling remains a challenge in active surveillance programmes.

PATIENTS AND METHODS

This was a retrospective study from an academic centre, of men with prostate cancer treated from 2000 to 2007, with a PSA level of <10 ng/mL and one core of cancer from an extended scheme showing either Gleason score (GS) 3 + 3 of <3.0 mm or 3 + 4 of <2.0 mm. All men had RP, and the TTV, DTV, tumour location, pathological GS and stage were measured.

RESULTS

Of 3055 RPs, 66 (2.1%) met the inclusion criteria. The core with cancer was from a sextant and alternative site in 26 (39%) and 40 (61%) patients, respectively. A pathological GS 3 + 3 or 3 + 4 was assigned to 94%, while 6% were GS ≥ 4 + 3; all 66 tumours were organ‐confined. The median (range) TTV and DTV were 0.15 (0.0008–5.06) and 0.14 (0.0008–5.04) mL, respectively. The median number of tumour foci was 3 (1–7), being unifocal in 17/66 (26%) and multifocal in 49/66 (74%). The transition zone was involved in 29% of unifocal and 71% of multifocal tumours. Of all 66 patients, the TTV was <0.5 mL in 47 (71%), and of 59 patients with biopsy GS 3 + 3, 33 (56%) had a TTV of <0.5 mL and pathological GS 3 + 3. Of 19 patients with a TTV of ≥0.5 mL, the median TTV was 1.06 (0.51–5.05) mL, with tumour foci of transition zone origin in 16 (84%). The study was limited by its retrospective design and small sample size.

CONCLUSIONS

Using conservative selection criteria for predicting LV/LG cancer, RP specimens showed organ‐confined disease in all cases, upgrading to GS ≥ 4 + 3 in 6%, and TTV <0.5 mL in 71% of cases. The transition zone is a common location of under‐sampled disease.
Novel in vitro model for studying ureteric stent‐induced cell injury
Authors: Elwood Chelsea N. , Lange Dirk , Nadeau Richard , Seney Shannon , Summers Kelly , Chew Ben H. , Denstedt John D. , Cadieux Peter A.
Published: November 2009

OBJECTIVE

To develop a novel in vitro model for the study of bladder and kidney epithelial cell injury akin to stent movement, as ureteric stents are associated with urinary tract complications that can significantly add to patient morbidity. These sequelae may be linked to inflammation triggered by stent‐mediated mechanical injury to the urinary tract.

MATERIALS AND METHODS

T24 bladder and A498 kidney cell line monolayers were damaged mechanically by segments of either Percuflex Plus® (PP) or Triumph® (triclosan‐eluting) stents (both from Boston Scientific Corporation Inc. Natick, MA, USA) and the resulting expression profiles of several pro‐inflammatory cytokines and growth factors were analysed.

RESULTS

After control injury using the PP stent, supernatants of both cell lines had significantly increased levels of interleukin (IL)‐6, IL‐8, basic fibroblast growth factor and platelet‐derived growth factor BB, and A498 cells also had increased tumour necrosis factor α. In almost all cases, the presence of triclosan within the media abrogated the pro‐inflammatory cytokine increases, while its effects on growth factors varied.

CONCLUSION

This study suggests that stent‐related symptoms in the bladder and kidney may be partially due to a local inflammatory response to epithelial damage caused by the presence and movement of the stent. Future stent design should take these inflammatory responses, with respect to physical injury, into consideration, using either more biocompatible materials or anti‐inflammatory compounds such as triclosan.
Is statin use associated with prostate cancer aggressiveness?
Authors: Loeb Stacy , Kan Donghui , Helfand Brian T. , Nadler Robert B. , Catalona William J.
Published: November 2009

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To further examine the association between statins (3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors) and pathological features in a large group of patients undergoing radical prostatectomy (RP), as epidemiological studies have suggested that statins, in addition to their beneficial cardiovascular effects, might reduce the risk of aggressive prostate cancer.

PATIENTS AND METHODS

From 2003 to 2009, 1351 men with data on preoperative statin use had RP by one surgeon. The clinical and pathological tumour features were compared between 504 users of statins and 847 who were not users.

RESULTS

Statin users were significantly older and had a higher mean body mass index than non‐users. The preoperative serum prostate‐specific antigen levels, tumour volume and percentage of cancer in the RP specimen were significantly lower in patients taking statins. Overall, statin users had a proportionately lower rate of adverse tumour pathology features, including a significantly lower risk of positive (cancerous) surgical margins.

CONCLUSION

Our results suggest that the use of statins might be associated with more favourable pathological features at RP. The long‐term disease‐specific outcomes and the underlying link between statins and prostate cancer require further investigation.
Anorectal malformations: what happens in adulthood?
Authors: Davies Melissa C. , Liao Lih‐Mei , Wilcox Duncan T. , Woodhouse Christopher R.J. , Creighton Sarah M.
Published: November 2009

Study Type – Prognosis (case series) Level of Evidence 4

OBJECTIVE

To comprehensively evaluate the outcomes in adults who were born with anorectal malformations (ARMs), to assess the relationships between the major types of ARM and outcomes, and to examine the relationships between bowel and urinary function and sexual well‐being, as advances in surgical treatment for ARMs have led to more patients surviving into adult life, and adult data on urinary and bowel function are scant, with even less known about the effect of diagnosis and treatment on sexual and reproductive function.

PATIENTS AND METHODS

In all, 74 adult patients with a diagnosis of ARM confirmed by review of paediatric medical records completed a series of validated questionnaires on urinary and bowel function, body esteem, sexual well being, fertility and overall quality of life.

RESULTS

There were high levels of urinary and bowel incontinence for both men and women. A high ARM was associated with a greater degree of incontinence. Both men and women scored more poorly than controls on the body esteem, sexual well‐being and quality‐of‐life assessments. Urinary and bowel incontinence was associated with poorer sexual well‐being.

CONCLUSIONS

Bowel and urinary outcomes in adults appear to be worse than suggested in paediatric reports, with high levels of both urinary and fecal incontinence. Poorer outcomes appeared to affect sexual well‐being adversely. To date, attention to issues during transition from childhood to adulthood, particularly concerns about sexual function and well‐being, has been conspicuous by its absence. Patient‐focused multidisciplinary care during this transition must address these issues, which are central to an acceptable quality of life.
Reducing blood loss in open radical retropubic prostatectomy with prophylactic periprostatic sutures
Authors: Carvalhal Gustavo F. , Griffin Christopher R. , Kan Donghui , Loeb Stacy , Catalona William J.
Published: November 2009

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To determine whether the placement of small‐calibre, rapidly absorbed prophylactic periprostatic sutures before the mobilization of the prostate could reduce blood loss during open retropubic radical prostatectomy (RRP).

PATIENTS AND METHODS

In 2007, during open RRP, we began placing prophylactic haemostatic sutures of 4‐0 and 3‐0 plain catgut in the anterior portions of the distal neurovascular bundles (NVBs) and lateral to the proximal NVBs and prostate pedicles before initiating the nerve‐sparing dissection and mobilizing the prostate gland. To evaluate whether this reduced intraoperative blood loss, we compared estimated blood loss (EBL), non‐autologous transfusion rates, and postoperative haemoglobin (Hb) levels between 100 consecutive patients treated immediately before and 100 consecutive patients treated immediately after the adoption of the prophylactic periprostatic suture technique.

RESULTS

Before the use of prophylactic haemostatic sutures, the mean intraoperative blood loss was 1285 mL, and one patient (1%) received an intraoperative non‐autologous transfusion. After the adoption of prophylactic sutures, the mean EBL was 700 mL (P < 0.001), and there were no transfusions. The mean Hb concentration the morning after RRP was 10.9 g/dL before and 11.8 g/dL after the initiation of prophylactic haemostatic sutures (P < 0.001).

CONCLUSION

Prophylactic periprostatic haemostatic sutures significantly reduce intraoperative blood loss during open RRP.
A STUDY OF SPACE IN MUMBAI'S SLUMS
Authors: NIJMAN JAN
Published: November 2009

The urban slum in the less developed world has an overwhelming significance of place for its dwellers: it determines who they are, what they do, where they go, and whom they know. Unlike most Western cities where the different realms of life (residential, work, religious, public, etc.) are spatially segregated, here they are all functionally and spatially integrated. A close examination of slum spaces in Dharavi, Mumbai, reveals such overlapping spatial patterns and raises some fundamental questions. Is there a proper definition of the slum? How should we conceive of the slum community and its spatial features? How useful or problematic are Western concepts of residential segregation, ghettos and enclaves? It is argued that the historical persistence of urban slums points to their indispensability, with the tacit (if inconsistent) approval of the state. Slums not only provide shelter to a large urban labour force but also a milieu that is conducive to intense social organisation and economic production.
A Reflective Review of Disruptive Innovation Theory
Authors: Yu Dan , Hang Chang Chieh
Published: November 2009

Disruptive Innovation Theory has created a significant impact on management practices and aroused plenty of rich debate within academia. Copious as the studies are, the scattered and conflicting nature of the literature on disruptive innovation in the last decade may pose a state of ambiguity for future research, thus necessitating a comprehensive review at this juncture. This paper first clarifies the basic concept and potential misinterpretations of the theory. Believing in the predictive value of the theory on firm performance, the authors then summarize and critique the research on how to enable potential disruptive innovation from internal, external, marketing and technology perspectives. The different perspectives inspired the authors to identify a number of key research directions within the disruptive innovation research domain. Potential future research is also briefly discussed by integrating disruptive innovation with other research domains, such as open innovation. Finally, in addition to theoretical contributions, the authors make practical contributions by outlining a series of potential inhibitors and enablers of disruptive innovation as managerial ‘take‐aways’.
Drying stress and damage processes in human stratum corneum
Authors: Levi K. , Weber R. J. , Do J. Q. , Dauskardt R. H.
Published: November 2009

Synopsis

The drying stresses that develop in stratum corneum (SC) are crucial for its mechanical and biophysical function, its cosmetic feel and appearance, and play a central role in processes of dry skin damage. However, quantitative methods to characterize these stresses are lacking and little understanding exists regarding the effects of drying environment, chemical exposures and moisturizing treatments. We describe the application of a substrate curvature technique adapted for biological tissue to accurately characterize SC drying stresses as a function of time following environmental pre‐conditioning and chemical treatment in a range of drying environments. SC stresses were observed to increase to stress levels of up to ∼ 3 MPa over periods of 8 h depending on pretreatment and drying environment. A unique relationship between the SC stress and water in the drying environment was established. The effect of glycerol on lowering SC stresses and damaging surfactants on elevating SC stresses were quantified. Extensions of the method to continuous monitoring of SC stresses in response to changes in environmental moisture content and temperature are reported. Finally, a biomechanics framework to account for the SC drying stress as a mechanical driving force for dry skin damage is presented.
Employment Experiences, Perspectives, and Wishes of Mothers of Children with Autism in the People’s Republic of China
Authors: McCabe Helen
Published: November 2009

Background  The purpose of this study was to examine the experiences with and meaning of employment in the lives of mothers of children with autism in China.

Materials and Methods  This research used qualitative methods including open‐ended questionnaires and semi‐structured interviews with mothers of children with autism participating in an intervention program in Beijing.

Results  Mothers find employment outside the home appealing, but they also see their role of mother as requiring being responsible and often making sacrifices.

Conclusions  Mothers in this study make sacrifices in their own lives, including employment, in order to promote and provide intervention for their children with autism. These families had fewer services available to them than in many developed Western countries, and most services are at a cost to the parents. Considerations that Chinese mothers of children with autism make regarding their own employment situation are unique.
Rehabilitation of Low Vision in Adults with Intellectual Disabilities: The Influence of Staff
Authors: Sjoukes Liesbeth , Kooijman Aart , Koot Hans , Evenhuis Heleen
Published: November 2009

Background  We explored to what extent carers act on treatment and rehabilitation advice for low vision in intellectual disability (ID) services and how this relates to their familiarity with and appreciation of the advice.

Methods  We followed prospectively 60 adults with a recent diagnosis of low vision during 12 months after their individual intervention advice. Questionnaire scores of carers’ familiarity with and appreciation of the advice and the quality of implementation were analysed using Spearman’s correlation.

Results  Familiarity with the advice was reasonable or good in 41/60, appreciation was positive in 34/60, and implementation was reasonable to complete in 20/60 cases. Familiarity, appreciation and implementation were not significantly related to severity of ID or severity of visual impairment. Implementation was positively correlated with familiarity (Spearman’s ρ = 0.602, P < 0.001) but not with appreciation (Spearman’s ρ = 0.224; P = 0.086).

Conclusion  It is important to keep professional carers knowledgeable and informed to improve the quality of low vision rehabilitation.
Training Staff to Manage Challenging Behaviour
Authors: Van Oorsouw Wietske M. W. J. , Embregts Petri J. C. M. , Bosman Anna M. T. , Jahoda Andrew
Published: November 2009

Background  A training package for staff working with clients presenting challenging behaviour was developed to (1) increase their knowledge regarding challenging behaviour, and (2) to improve the quality of physical intervention techniques. The latter aim was intended to reduce staff anxiety about dealing with incidents and limit physical risk of injury to both clients and themselves.

Materials and Methods  Sessions concerning theories of challenging behaviour were combined with physical intervention training. Effectiveness was assessed using knowledge questionnaires and observation of staff skills. Training effectiveness was tested in a pre–post‐test control group design.

Results and Conclusions  The training program proved to be effective. Staff knowledge of challenging behaviour and the quality of physical intervention techniques increased significantly. Scores remained above pre‐test levels at follow‐up. Staff members evaluated the training positively.
Toxicological evaluation of azumolene after repeated intraperitoneal administration in rats
Authors: Do Carmo Paula Lima , Zapata‐Sudo Gisele , Trachez Margarete Manhães , Das Graças Fernandes Sales Maria , Sudo Roberto Takashi
Published: November 2009

We investigated the toxicity of azumolene (Az), a more water‐soluble compound than dantrolene, after 14 days of intraperitoneal (i.p.) administration in rats at doses of 1, 2.5 or 10 mg/kg/day. No animals died or presented signs of toxicity. No significant differences in water and food consumption or weight gain were noted among the groups. Blood analysis revealed no significant alteration by Az treatment in the number of blood cells. However, Az treatment induced a perivascular inflammatory reaction in the liver and non‐diffuse necrosis of skeletal muscle, both of which occurred only at the highest dose of Az and were completely reversed 14 days after cessation of treatment. Congestion and inflammation in the kidneys were only partially reversed. Caffeine‐induced contracture of skeletal muscle was not altered during 7 days of i.p. injection of Az (2.5 mg/kg/day). In conclusion, Az is a safe compound for long‐term administration, but does cause a mild, reversible reaction in skeletal muscle and kidney.
Pharmacological doses of vitamin A increase caspase‐3 activity selectively in cerebral cortex
Authors: De Oliveira Marcos Roberto , Oliveira Max William Soares , Moreira José Cláudio Fonseca
Published: November 2009

Vitamin A exerts a wide range of physiological roles from embryonic to adulthood stages of the mammalian life. However, there is a great concern regarding the deleterious effects of vitamin A use even therapeutically. It was shown that vitamin A induces behavioral impairments, for instance, anxiety‐like behavior and depression, in experimental animals and humans. Caspases are enzymes associated with cell death; however, there is a role for such enzymes also in synaptic plasticity. Then, based on previously published data, we have investigated the effects of vitamin A supplementation at clinical doses (1000–9000 IU/kg/day) for 28 days on caspase‐3 and caspase‐8 activities in adult rat cerebral cortex, cerebellum, striatum, and hippocampus. Furthermore, we have quantified TNF‐α levels, a pro‐inflammatory cytokine that, besides other biological roles, trigger the extrinsic apoptotic pathway in several cellular types, in those rat brain regions. Interestingly, we found increased caspase‐3 activity only in rat cerebral cortex. In all the other regions caspase‐3 and caspase‐8 activities did not change, as well as the levels of TNF‐α. The presented results, herein, indicate that more caution is needed regarding vitamin A clinical use and, also importantly, the consumption of vitamin A‐fortified foods, which are not exclusively distributed among vitamin A‐deficient subjects.
Levetiracetam inhibits glutamate transmission through presynaptic P/Q‐type calcium channels on the granule cells of the dentate gyrus
Authors: Lee Chun‐Yao , Chen Chih‐Chuan , Liou Horng‐Huei
Published: November 2009

Background and purpose: Levetiracetam is an effective anti‐epileptic drug in the treatment of partial and generalized seizure. The purpose of the present study was to investigate whether levetiracetam regulates AMPA and NMDA receptor‐mediated excitatory synaptic transmission and to determine its site of action in the dentate gyrus (DG), the area of the hippocampus that regulates seizure activities.

Experimental approach: Whole‐cell patch‐clamp method was used to record the AMPA and NMDA receptor‐mediated excitatory postsynaptic currents (EPSCAMPAand EPSCNMDA) in the presence of specific antagonists, from the granule cells in the DG in brain slice preparations from young Wistar rats (60–120 g).

Key results: Levetiracetam (100 µM) inhibited both evoked EPSCAMPAand EPSCNMDAto an equal extent (80%), altered the paired‐pulse ratio (from 1.39 to 1.25), decreased the frequency of asynchronous EPSC and prolonged the inter‐event interval of miniature EPSCAMPA(from 2.7 to 4.6 s) without changing the amplitude, suggesting a presynaptic action of levetiracetam. The inhibitory effect of levetiracetam on evoked EPSCAMPAwas blocked by ω‐agatoxin TK (100 nM), a selective P/Q‐type voltage‐dependent calcium channel blocker, but not by nimodipine (10 µM) or ω‐conotoxin (400 nM).

Conclusions and implications: These results suggest that levetiracetam modulated the presynaptic P/Q‐type voltage‐dependent calcium channel to reduce glutamate release and inhibited the amplitude of EPSC in DG. This effect is most likely to contribute to the anti‐epileptic action of levetiracetam in patients.
Geranylgeraniol prevents the cytotoxic effects of mevastatin in THP‐1 cells, without decreasing the beneficial effects on cholesterol synthesis
Authors: Campia I , Lussiana C , Pescarmona G , Ghigo D , Bosia A , Riganti C
Published: November 2009

Background and purpose:  Statins, inhibitors of hydroxymethylglutaryl‐CoA reductase, reduce the intracellular synthesis of cholesterol and prevent the onset of atherosclerosis. They also decrease the synthesis of isoprenoid molecules, such as the side chain of ubiquinone and geranylgeranyl pyrophosphate. As a consequence, statins impair mitochondrial metabolism and the activation of small monomeric GTPases (such as Rho and Ras), causing toxic effects. To date, a successful strategy to prevent statin toxicity is lacking.

Experimental approach:  In human monocytic THP‐1 cells, we measured the synthesis of cholesterol and isoprenoids, mitochondrial electron flow, the activity of RhoA and Rac, cell death and proliferation.

Key results:  Mevastatin reduced the synthesis of cholesterol, geranylgeranyl pyrophosphate and ubiquinone, mitochondrial electron transport, activity of RhoA and Rac, and cell proliferation, accompanied by increased cell death. Geranylgeraniol, a cell‐permeable analogue of geranylgeranyl pyrophosphate, reversed all these effects of mevastatin, without affecting its ability to reduce cholesterol synthesis. Notably, geranylgeraniol was more effective than the addition of exogenous ubiquinone, which rescued mitochondrial respiratory activity and reversed mevastatin cytotoxicity, but did not alter the decrease in cell proliferation. The same results were obtained in human liver HepG2 cells.

Conclusions and implications:  Geranylgeraniol had a broader protective effect against the cytotoxicity of statins than exogenous ubiquinone. Therefore, geranylgeraniol may be a more useful and practical means of limiting the toxicities of statins, without reducing their efficacy as cholesterol lowering agents.
Characterization of the oestrogenic activity of non‐aromatic steroids: are there male‐specific endogenous oestrogen receptor modulators?
Authors: Wang Pan , Wen Yujing , Han Gui‐Zhen , Sidhu Pritam Kaur , Zhu Bao Ting
Published: November 2009

Background and purpose:  The endogenous oestrogens have important biological functions in men as well as in women. Because 17β‐oestradiol and oestrone are also formed in the male body, these aromatic oestrogens are generally thought to be responsible for exerting the required oestrogenic functions in the male. In the present study, we tested the hypothesis that some of the non‐aromatic steroids that are androgen precursors or metabolites with hydroxyl groups at C‐3 and/or C‐17 positions may also be able to serve as ligands for the oestrogen receptors (ER) in the male.

Experimental approach:  A total of sixty non‐aromatic steroids (selected from families of androstens, androstans, androstadiens, oestrens and oestrans) were analysed for their ability to bind and activate the human ERα and ERβin vitro and in cultured cells.

Key results:  Six of the non‐aromatic steroids, that is, 5‐androsten‐3β,17β‐diol, 5α‐androstan‐3β,17β‐diol, 5(10)‐oestren‐3α,17β‐diol, 5(10)‐oestren‐3β,17β‐diol, 4‐oestren‐3β,17β‐diol and 5α‐oestran‐3β,17β‐diol, were found to have physiologically relevant high binding affinity (∼50% of that of oestrone) for human ERα and ERβ. These non‐aromatic steroids also activated the transcriptional activity of human ERs and elicited biological responses (such as growth stimulation) in two representative ER‐positive human cancer cell lines (MCF‐7 and LNCaP) with physiologically relevant potency and efficacy. Molecular docking analysis of these six active compounds showed that they could bind to ERα and ERβ in a manner similar to that of 17β‐oestradiol.

Conclusions and implications:  These results provide evidence for the possibility that some of the endogenous androgen precursors or metabolites could serve as male‐specific ER ligands.
Basal hypercortisolism and trauma in patients with psychogenic nonepileptic seizures
Authors: Bakvis Patricia , Spinhoven Philip , Giltay Erik J. , Kuyk Jarl , Edelbroek Peter M. , Zitman Frans G. , Roelofs Karin
Published: November 2009

Purpose:  Several studies have indicated that psychogenic nonepileptic seizures (PNES) are associated with psychological trauma, but only a few studies have examined the associations with neurobiologic stress systems, such as the hypothalamus–pituitary–adrenal (HPA) axis and its end‐product cortisol. We tested several relevant HPA‐axis functions in patients with PNES and related them to trauma history.

Methods:  Cortisol awakening curve, basal diurnal cortisol, and negative cortisol feedback (using a 1 mg dexamethasone suppression test) were examined in 18 patients with PNES and 19 matched healthy controls (HCs) using saliva cortisol sampling on two consecutive days at 19 time points. Concomitant sympathetic nervous system (SNS) activity was assessed by analyzing saliva α‐amylase (sAA).

Results:  Patients with PNES showed significantly increased basal diurnal cortisol levels compared to HCs. This effect was driven mainly by patients reporting sexual trauma who showed a trend toward higher cortisol levels as compared to patients without a sexual trauma report. Importantly, the increased basal diurnal cortisol levels in patients were not explained by depression, medication, or smoking, or by current seizures or group differences in SNS activity.

Discussion:  This is the first study showing that basal hypercortisolism in patients with PNES is independent of the acute occurrence of seizures. In addition, basal hypercortisolism was more pronounced in traumatized patients with PNES as compared to nontraumatized patients with PNES. These findings suggest that HPA‐axis activity provides a significant neurobiologic marker for PNES.
Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies
Authors: Kwan Patrick , Arzimanoglou Alexis , Berg Anne T. , Brodie Martin J. , Allen Hauser W. , Mathern Gary , Moshé Solomon L. , Perucca Emilio , Wiebe Samuel , French Jacqueline
Published: November 2009

To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two “hierarchical” levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.
Aluminum Stock and Flows in U.S. Passenger Vehicles and Implications for Energy Use
Authors: Cheah Lynette , Heywood John , Kirchain Randolph
Published: November 2009

In this article, a methodology to model the annual stock and flows of aluminum in a key end‐use sector in the United States—passenger vehicles—from 1975–2035 is described. This dynamic material flow model has enabled analysis of the corresponding energy embodied in automotive aluminum as well as the cumulative aluminum production energy demand. The former was found to be significant at 2.6 × 109 gigajoules (GJ) in year 2008 under baseline assumptions. From 2008–2035, the cumulative energy required to produce aluminum to be used in vehicles is estimated at 7.8 × 109 GJ. Although the automotive aluminum stock is expected to increase by 1.8 times by 2035, the corresponding energy embodied is not expected to grow as rapidly due to efficiency improvements in aluminum processing over time. The model's robustness was tested by checking the sensitivity of the results to variations in key input assumptions, including future vehicle sales, lifetimes, and scrap recovery. Sensitivity of energy embodied in automotive aluminum to changes in aluminum production efficiency and aluminum applications within the vehicle were also explored. Using more recycled aluminum or improving the energy efficiency of aluminum production at a faster rate can lower production energy demands. However, aggressive and sustained changes are needed beginning today to achieve meaningful reductions. This may potentially be countered by increased use of stamped aluminum in vehicles.
Do Problems with Information Processing Affect the Process of Psychotherapy for Adults with Learning Disabilities or Attention Deficit/Hyperactivity Disorder?
Authors: Cosden Merith , Patz Sarah , Smith Steven
Published: November 2009

Problems in processing information can affect psychosocial functioning. Psychotherapy can be used to address psychosocial problems; however, the same information–processing problems that contribute to disabilities, such as learning disabilities (LD) or attention deficit/hyperactivity disorder (ADHD), particularly deficits in auditory processing and attention, may also interfere with the process of psychotherapy. Using a Web–based survey, data dealing with perceptions of the effectiveness of psychotherapy were obtained from 52 adult patients with LD and/or ADHD and 87 adults who did not have any diagnosed cognitive difficulties. While all respondents reported psychotherapy was helpful, those with LD were less likely than others to seek therapy again and reported a greater need for more accommodations. Respondents with auditory processing problems were less likely than others to meet treatment goals. Overall, 44 percent of patients with a diagnosed disability indicated the condition affected therapy. Clients’ descriptions of the impact of their disabilities on psychotherapy, and need for accommodations, are presented. Implications for both clients and therapists are discussed.
Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia
Authors: BAILIE George R. , MASON Nancy A. , VALAORAS Thomas G.
Published: November 2009

There is limited safety information about ferric carboxymaltose (FCM), a new intravenous iron preparation. This randomized, crossover study compared the safety and tolerability of double‐blinded intravenous doses of FCM or placebo in patients with iron deficiency anemia. Subjects (559) with iron deficiency anemia received a dose of either FCM (15 mg/kg, maximum 1000 mg) over 15 minutes or placebo on day 0. On day 7, subjects received the other agent. Safety evaluations were performed on days 7 and 14. The primary endpoint was the incidence of treatment‐emergent adverse events during each 7‐day study period. During the first 24 hours and during the 7‐day treatment period, at least one treatment‐emergent adverse event was experienced by 15.0% and 29.3% of subjects after FCM and 11.4% and 19.7% after placebo, respectively. Most were classified as Grade 1 or 2. Six subjects had Grade 3 treatment‐emergent adverse events after FCM and 9 subjects after placebo. One subject had a Grade 4, and 1 subject had a Grade 5 treatment‐emergent adverse event, but neither was considered study drug‐related. During the first 24 hours of the treatment period, drug‐related adverse events were reported in 9.3% of subjects receiving FCM and 4.8% receiving placebo. Of drug‐related Grade 3 events, 4 subjects received FCM and 5 subjects received placebo. Administration of FCM (15 mg/kg, maximum of 1000 mg) over 15 minutes was well tolerated and associated with minimal risk of adverse reactions in patients with iron deficiency anemia.
C.E.R.A. once every 4 weeks in patients with chronic kidney disease not on dialysis: The ARCTOS extension study
Authors: KESSLER Michèle , MARTÍNEZ‐CASTELAO Alberto , SIAMOPOULOS Kostas C. , VILLA Giuseppe , SPINOWITZ Bruce , DOUGHERTY Frank C. , BEYER Ulrich
Published: November 2009

C.E.R.A., a continuous erythropoietin receptor activator is approved for the treatment of anemia in patients with chronic kidney disease (CKD). The ARCTOS (administration of C.E.R.A. in CKD patients to treat anemia with a twice‐monthly schedule) phase 3 study demonstrated the efficacy and safety of C.E.R.A. in correcting anemia when administered once every 2 weeks (Q2W) subcutaneously in patients with CKD not on dialysis. We assessed the feasibility and long‐term safety of converting patients who responded to treatment with C.E.R.A. Q2W to C.E.R.A. once every 4 weeks (Q4W) during a 24‐week extension period. After the core ARCTOS study period (28 weeks), 296 patients entered the 24‐week extension period. At week 29, patients who responded to C.E.R.A. Q2W during the core period were rerandomized to receive subcutaneous C.E.R.A. Q2W or Q4W. Patients in the comparator arm could receive darbepoetin alfa once weekly or Q2W. Dosage was adjusted to maintain hemoglobin (Hb) between 11 and 13 g/dL. Mean Hb levels remained stable in all groups, and were comparable at the end of the extension period (mean [standard deviation], C.E.R.A. Q2W, 11.92 [0.90] g/dL; C.E.R.A. Q4W, 11.70 [0.86] g/dL; darbepoetin alfa, 11.89 [0.98] g/dL). Mean within‐patient standard deviation values for Hb were also comparable in all groups (0.66, 0.62, and 0.65 g/dL for C.E.R.A. Q2W, C.E.R.A. Q4W and darbepoetin alfa, respectively). All treatments were well tolerated. Subcutaneous C.E.R.A. Q4W is safe and effective in maintaining stable Hb levels in patients with CKD not on dialysis following correction with subcutaneous C.E.R.A. Q2W.
Responsibility in Childhood: Three Developmental Trajectories
Authors: Ochs Elinor , Izquierdo Carolina
Published: November 2009

AbstractIn this article, we analyze the development of responsibility through the lens of the Peruvian Matsigenka, Samoan, and middle‐class Los Angeles, California, childhoods. We propose that recognizing social awareness, social responsiveness, and self‐reliance as keystone properties of responsibility supports an argument that children's routine work at home enables not only social but also moral responsibility, in the form of respectful awareness of and responsiveness to others' needs and reliance on knowledge that takes into consideration others' judgments. We document distinct modes of engagement in community and family activities evidenced in community ethnographies of children in Matsigenka, Samoa, and in middle‐class Los Angeles, and propose seven arguments (related to sociopolitical organization, necessity, development, school priority, independence–interdependence, attention practices, and inconsistency) that bear on these observations. A contradiction in the values and practices for promoting independence and giving care is manifested exclusively in the L.A. families, creating a dependency dilemma for children of these families. If moral responsibility involves an active turning toward the other that engenders the capacity for compassion, our research indicates childhood socialization practices differentially facilitate or complicate achievement of this perspective. [responsibility, child development, socialization, Samoa, Los Angeles, Matsigenka]
“Do You Know Who You Are?” Radical Existential Doubt and Scientific Certainty in the Search for the Kidnapped Children of the Disappeared in Argentina
Authors: Gandsman Ari
Published: November 2009

AbstractDuring the Argentine military dictatorship (1976–83) up to 30,000 people disappeared. Included among them were an estimated 500 children who were handed over to families related (or with close ties) to security forces.The Grandmothers of the Plaza de Mayoformed to discover their fate. During the 1980s, theGrandmothersused newly available genetic technologies as a means of verifying the identities of potential grandchildren to reunite them with their biological families. In the 1990s, custody was no longer an issue because the children were legally adults. Forced to change their strategy, they embarked on public campaigns directing those with “doubts about their identity” to contact the organization. This article provides an ethnographic analysis of these public campaigns to advance theoretical perspectives on the nature of embodied truth and the transformation of individual concerns regarding personal identity to collective doubt regarding national identity and belonging. [identity, human rights, genetics, history, politics, memory]