bluuebunny/crossref_metadata_2025 huggingface dataset:
Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A: safety, efficacy and pharmacokinetics
Authors: Kulkarni R. , Karim F. A. , Glamocanin S. , Janic D. , Vdovin V. , Ozelo M. , Rageliene L. , Carboni E. , Laguna P. , Dobaczewski G. , Seremetis S. , Lindblom A. , Santagostino E.
Published: May 2013

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open‐label, non‐controlled trial investigated the safety, efficacy and pharmacokinetics (PK) of turoctocog alfa, a new rFVIII product, in a paediatric population. The primary objective was to evaluate safety. A total of 31 younger children (0–5 years) and 32 older children (6–11 years), with ≥50 exposure days to any factor VIII (FVIII) product and no history of inhibitors, received prophylaxis with turoctocog alfa (25–50 IU kg−1 every second day or 25–60 IU kg−1 three times weekly). PK assessments of turoctocog alfa and the patients’ previous FVIII product were performed in 28 patients. Mean exposure to turoctocog alfa was 60 exposure days per patient. This corresponds to approximately 4.5 months in the trial. None of the patients developed inhibitors (≥0.6 BU) and no safety concerns were raised. A total of 120 bleeding episodes (95%) were controlled with 1–2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as ‘excellent’ or ‘good’ haemostatic response) for treatment of bleeding episodes was 92%. Overall, the median annualized bleeding rate was 3.0 (interquartile range: 8.5) bleeds patient−1 year−1. PK parameters were comparable between the two age groups. In conclusion, the present large global clinical trial showed that turoctocog alfa was safe, effective in treatment of bleeding episodes and had a prophylactic effect in paediatric patients.
Undermining patient and public engagement and limiting its impact: The consequences of the Health and Social Care Act 2012 on collective patient and public involvement
Authors: Tritter Jonathan Q , Koivusalo Meri
Published: May 2013

Patient and public involvement has been at the heart of UK health policy for more than two decades. This commitment to putting patients at the heart of the British National Health Service (NHS) has become a central principle helping to ensure equity, patient safety and effectiveness in the health system. The recent Health and Social Care Act 2012 is the most significant reform of the NHS since its foundation in 1948. More radically, this legislation undermines the principle of patient and public involvement, public accountability and returns the power for prioritisation of health services to an unaccountable medical elite. This legislation marks a sea‐change in the approach to patient and public involvement in the UK and signals a shift in the commitment of the UK government to patient‐centred care.
Solutions to the Exploration/Exploitation Dilemma: Networks as a New Level of Analysis
Authors: Stadler Christian , Rajwani Tazeeb , Karaba Florence
Published: May 2013

This paper reviews the extant literature on the exploration/exploitation dilemma. Based on a systematic analysis of structural, behavioural, systemic and temporal solutions, the authors are able to show that the learning literature continues to struggle with the question of how exactly an organization can separate exploration and exploitation and at the same time enable necessary knowledge exchange and cooperation between these two notions. Paying closer attention to networks might enable future research to answer this question. In particular, a combination of structural aspects of networks and social ties has the potential to explain how the solutions currently on offer can be implemented successfully, how organizations can combine several of them, and how they can shift between them.
A case of nicorandil‐induced unilateral corneal ulceration
Authors: Trechot Fanny , Batta Benjamine , Petitpain Nadine , Bazard Marie C , Angioi Karine , Trechot Philippe
Published: May 2013

Nicorandil, a second‐generation nitro derivative, has been reported to induce single or multiple ulcerations in many locations, including oral, anal, perianal, vulvovaginal, perivulval, penile, gastrointestinal, colic, peristomal and skin locations. Ocular locations are now highly suspected. Herein, we report the case of a 78‐year‐old woman who experienced corneal ulceration at second cataract surgery (right eye) while being treated with nicorandil for 3 years. Four years before, she had had an uneventful first cataract surgery (left eye). The ulcers healed within 6 weeks after simple withdrawal of nicorandil, an expected delay for this type of chemical ulcer. The substitution of nicorandil with classic nitric oxide donors has already been done without complication. Surgical intervention is unnecessary and inappropriate. Case reports of ocular side effects induced by nicorandil are rare and probably underestimated.
AtMYB44 regulates resistance to the green peach aphid and diamondback moth by activating EIN2‐affected defences in Arabidopsis
Authors: Lü B.‐B. , Li X.‐J. , Sun W.‐W. , Li L. , Gao R. , Zhu Q. , Tian S.‐M. , Fu M.‐Q. , Yu H.‐L. , Tang X.‐M. , Zhang C.‐L. , Dong H.‐S.
Published: May 2013

Recently we showed that the transcription activator AtMYB44 regulates expression of EIN2, a gene essential for ethylene signalling and insect resistance, in Arabidopsis thaliana (Arabidopsis). To link the transactivation with insect resistance, we investigated the wild‐type and atmyb44 mutant plants, genetically Complemented atmyb44 (Catmyb44) and AtMYB44‐Overexpression Transgenic Arabidopsis (MYB44OTA). We found that AtMYB44 played a critical role in Arabidopsis resistance to the phloem‐feeding generalist green peach aphid (Myzus persicae Sulzer) and leaf‐chewing specialist caterpillar diamondback moth (Plutella xylostella L.). AtMYB44 was required not only for the development of constitutive resistance but also for the induction of resistance by both herbivorous insects. Levels of constitutive and herbivore‐induced resistance were consistent with corresponding amounts of the AtMYB44 protein constitutively produced in MYB44OTA and induced by herbivory in Catmyb44. In both cases, AtMYB44 promoted EIN2 expression to a greater extent in MYB44OTA than in Catmyb44. However, AtMYB44‐promoted EIN2 expression was arrested with reduced resistance levels in the EIN2‐deficient Arabidopsis mutant ein2‐1 and the MYB44OTA ein2‐1 hybrid. In the different plant genotypes, only MYB44OTA constitutively displayed phloem‐based defences, which are specific to phloem‐feeding insects, and robust expression of genes involved in the biosynthesis of glucosinolates, which are the secondary plant metabolites known as deterrents to generalist herbivores. Phloem‐based defences and glucosinolate‐related gene expression were not detected in ein2‐1 and MYB44OTA ein2‐1. These results establish a genetic connection between the regulatory role of AtMYB44 in EIN2 expression and the development of Arabidopsis resistance to insects.
Disproportionate effects of non‐colonial small herbivores on structure and diversity of grassland dominated by large herbivores
Authors: Rebollo Salvador , Milchunas Daniel G. , Stapp Paul , Augustine David J. , Derner Justin D.
Published: May 2013

The response of semiarid grasslands to small, non‐colonial herbivores has received little attention, focusing primarily on the effects of granivore assemblages on annual plant communities. We studied the long‐term effects of both small and large herbivores on vegetation structure and species diversity of shortgrass steppe, a perennial semiarid grassland considered marginal habitat for small mammalian herbivores. We hypothesized that 1) large generalist herbivores would affect more abundant species and proportions of litter‐bare ground‐vegetation cover through non‐selective herbivory, 2) small herbivores would affect less common species through selective but limited consumption, and 3) herbivore effects on plant richness would increase with increasing aboveground net primary production (ANPP). Plant community composition was assessed over a 14‐year period in pastures grazed at moderate intensities by cattle and in exclosures for large (cattle) and large‐plus‐small herbivores (additional exclusion of rabbits and rodents). Exclusion of large herbivores affected litter and bare ground and basal cover of abundant, common and uncommon species. Additional exclusion of small herbivores did not affect uncommon components of the plant community, but had indirect effects on abundant species, decreased the cover of the dominant grass Bouteloua gracilis and total vegetation, and increased litter and species diversity. There was no relationship between ANPP and the intensity of effects of either herbivore body size on richness. Exclusion of herbivores of both body sizes had complementary and additive effects which promoted changes in vegetation composition and physiognomy that were linked to increased abundance of tall and decreased abundance of short species. Our findings show that small mammalian herbivores had disproportionately large effects on plant communities relative to their small consumption of biomass. Even in small‐seeded perennial grasslands with a long history of intensive grazing by large herbivores, non‐colonial small mammalian herbivores should be recognized as an important driver of grassland structure and diversity.
Another call for the end of invasion biology
Authors: Valéry Loïc , Fritz Hervé , Lefeuvre Jean‐Claude
Published: May 2013

The restriction of invasion biology to non‐native species has been laid down as one founding principle of the discipline by many researchers. However, this split between native and non‐native species is highly controversial. Using a phenomenological approach and a more pragmatic examination of biological invasions, the present paper discusses how this dichotomy has restricted the relevance of the field, both from theoretical and practical viewpoints. We advocate the emergence of a broader disciplinary field.
Distribution patterns in generalized vitiligo
Authors: Speeckaert R. , van Geel N.
Published: May 2013

Background

Vitiligo is a common pigmentation disorder affecting approximately 1% of the world population. Nonetheless, its distribution pattern is not well investigated.

Objective

The aim of this study was to investigate whether the distribution pattern of vitiligo is dependent on the clinical characteristics.

Methods

A total of 700 generalized vitiligo patients were included in this retrospective observational cohort study.

Results

The most important predilection areas were the face (87%), followed by acral areas (76.3%) and extremities (59.7%). In women, joints (P = 0.002) (especially elbows), hips (P < 0.001), trunk (P < 0.001) and body folds (P < 0.001) (especially axillas) were more frequently affected compared to men. In contrast, in men more depigmentations in the beard area and genital area were observed (P < 0.001). Vitiligo at a young age is more prone to be localized at the lower extremities whereas the upper extremities are more susceptible at an older age. In the face, the periocular area is linked to a younger age, in contrast to the perioral area. Acral areas were more frequently affected in patients with autoimmune disorders (in particular thyroid disease) (P = 0.001).

Conclusion

These results point to important differences in the distribution pattern according to the clinical characteristics. Although in some of these areas Koebner's phenomenon probably plays a role, other differences may represent a specific characteristic vulnerability related to the age, gender or typical association with autoimmune disease.
Monitoring oriental fruit moth (Lepidoptera: Tortricidae) with the Ajar bait trap in orchards under mating disruption
Authors: Knight A. , Basoalto E. , Hilton R. , Molinari F. , Zoller B. , Hansen R. , Krawczyk G. , Hull L.
Published: May 2013

Studies in Oregon, California, Pennsylvania and Italy evaluated the relative performance of the Ajar trap compared with several other traps for the capture of Grapholita molesta (Busck), in pome and stone fruit orchards treated with sex pheromone dispensers for mating disruption. The Ajar is a delta‐shaped trap with a screened jar filled with an aqueous terpinyl acetate plus brown sugar bait solution (TAS) that opens inside the trap and is surrounded by a sticky liner. The TAS‐baited Ajar trap was evaluated with and without the addition of a sex pheromone lure and compared with a delta trap baited with a sex pheromone lure and a bucket trap filled with the TAS bait. Although the Ajar trap had a 90% lower evaporation of the TAS bait than the bucket trap, both of them caught similar numbers in the majority of the field tests of both sexes of G. molesta. The addition of the sex pheromone lure did not increase moth catches by the TAS‐baited Ajar trap. The TAS‐baited Ajar trap caught significantly greater numbers of moths than the sex pheromone‐baited delta trap in 18 of the 20 orchards. Few hymenopterans were caught in orange TAS‐baited Ajar traps, but the catch of flies and other moths relative to the target pest remained high. Flight tunnel and field tests evaluated the effect of several screen designs on the catches of G. molesta and non‐target species. All exclusion devices significantly reduced the catch of larger moths. However, designs that did not reduce the catch of male G. molesta did not reduce the catch of muscid flies. Exclusion devices with openings <7.0 mm significantly reduced the catch of female G. molesta. The addition of (E)‐β‐farnesene, (E)‐β‐ocimene or butyl hexanoate septa lures to TAS‐baited Ajar traps significantly increased total moth catch. The addition of (E)‐β‐ocimene also significantly increased female moth catch.
Increased prion protein processing and expression of metabotropic glutamate receptor 1 in a mouse model of Alzheimer's disease
Authors: Ostapchenko Valeriy G. , Beraldo Flavio H. , Guimarães Andre L. S. , Mishra Sanju , Guzman Monica , Fan Jue , Martins Vilma R. , Prado Vania F. , Prado Marco A. M.
Published: May 2013

Prion protein (PrPC), a glycosylphosphatidylinositol‐anchored protein corrupted in prion diseases, has been shown recently to interact with group I metabotropic glutamate receptors (mGluRs). Moreover, both PrPC and mGluRs were proposed to function as putative receptors for β‐amyloid in Alzheimer's disease. PrPC can be processed in neurons via α or β‐cleavage to produce PrPC fragments that are neuroprotective or toxic, respectively. We found PrPC α‐cleavage to be 2–3 times higher in the cortex of APPswe/PS1dE9 mice, a mouse model of Alzheimer's disease. A similar age‐dependent increase was observed for PrPC β‐cleavage. Moreover, we observed considerable age‐dependent increase in cortical expression of mGluR1, but not mGluR5. Exposure of cortical neuronal cultures to β‐amyloid oligomers upregulated mGluR1 and PrPC α‐cleavage, while activation of group I mGluRs increased PrPC shedding from the membrane, likely due to increased levels of a disintegrin and metalloprotease10, a key disintegrin for PrPC shedding. Interestingly, a similar increase in a disintegrin and metalloprotease10 was detected in the cortex of 9‐month‐old APPswe/PS1dE9 animals. Our experiments reveal novel and complex processing of PrPC in connection with mGluR overexpression that seems to be triggered by β‐amyloid peptides.

image

Prion protein (PrPC) and metabotropic glutamate receptors (mGluR) are implicated in Alzheimer's disease (AD). We found age‐dependent increase in PrPC processing, ADAM10 and mGluR1 levels in AD mouse model. These changes could be reproduced in cultured cortical neurons treated with Aβ peptide. Our findings suggest that increased levels of Aβ can trigger compensatory responses that may affect neuronal toxicity.
Choline transporter‐like protein 4 (CTL4) links to non‐neuronal acetylcholine synthesis
Authors: Song Pingfang , Rekow Stephen S. , Singleton Corey‐Ayne , Sekhon Harmanjatinder S. , Dissen Gregory A. , Zhou Minerva , Campling Barbara , Lindstrom Jon , Spindel Eliot R.
Published: May 2013

Synthesis of acetylcholine (ACh) by non‐neuronal cells is now well established and plays diverse physiologic roles. In neurons, the Na+‐dependent, high affinity choline transporter (CHT1) is absolutely required for ACh synthesis. In contrast, some non‐neuronal cells synthesize ACh in the absence of CHT1 indicating a fundamental difference in ACh synthesis compared to neurons. The aim of this study was to identify choline transporters, other than CHT1, that play a role in non‐neuronal ACh synthesis. ACh synthesis was studied in lung and colon cancer cell lines focusing on the choline transporter‐like proteins, a five gene family choline‐transporter like protein (CTL)1–5. Supporting a role for CTLs in choline transport in lung cancer cells, choline transport was Na+‐independent and CTL1–5 were expressed in all cells examined. CTL1, 2, and 5 were expressed at highest levels and knockdown of CTL1, 2, and 5 decreased choline transport in H82 lung cancer cells. Knockdowns of CTL1, 2, 3, and 5 had no effect on ACh synthesis in H82 cells. In contrast, knockdown of CTL4 significantly decreased ACh secretion by both lung and colon cancer cells. Conversely, increasing expression of CTL4 increased ACh secretion. These results indicate that CTL4 mediates ACh synthesis in non‐neuronal cell lines and presents a mechanism to target non‐neuronal ACh synthesis without affecting neuronal ACh synthesis.
Nursing students’ attitudes towards provision of sexual health care in clinical practice
Authors: Huang Cheng‐Yi , Tsai Li‐Ya , Tseng Tsui‐Hwa , Li Chi‐Rong , Lee Sheuan
Published: May 2013

Aims and objectives

To investigate nursing students' attitudes towards providing sexual health care in clinical practice and to identify associated factors.

Background

Sexual health care is an important component of holistic health care. Nurses' personal sexual knowledge and attitudes are shown to influence provision of sexual health care.

Design

This is a descriptive, cross‐sectional study.

Methods

We selected 146 senior nursing students by convenience sampling from nursing schools in two medical universities in central Taiwan. Data were collected using the Nursing Attitudes on Sexual Health Care scale developed based on the ‘Permission/Limited Information/Specific Suggestions/Intensive Therapy’ model. Higher scores indicated more positive attitudes.

Results

Participants' mean age was 22·15 years. Mean total Nursing Attitudes on Sexual Health Care scores ranged from 45–75 (61·40 ± 10·17). Nursing students' most positive attitudes towards Permission/Limited Information/Specific Suggestions/Intensive Therapy sexual healthcare interventions were at the Permission level, and least positive attitudes were at levels of Specific Suggestion and Intensive Therapy. The top three positive items were as follows: accept patients' expression of sexual concerns, initiate discussions and encourage patients to talk. Male nursing students had negative attitudes towards sexual healthcare interventions, which became more positive as age increased, especially at the Limited Information level.

Conclusions

Nursing students had different attitudes towards different levels of sexual health care in the Permission/Limited Information/Specific Suggestions/Intensive Therapy model. Attitudes were associated with age and gender. The Nursing Attitudes on Sexual Health Care scale is useful and reliable for identifying nurses' attitudes towards providing sexual health care.

Relevance to clinical practice

The Permission/Limited Information/Specific Suggestions/Intensive Therapy‐based Nursing Attitudes on Sexual Health Care scale helps to identify nurses' attitudes. A better understanding of nurses' attitudes towards provisional sexual health care will provide information needed to develop appropriate education programmes to improve delivery of sexual health care.
Executive dysfunction is independently associated with reduced functional independence in heart failure
Authors: Alosco Michael L , Spitznagel Mary Beth , Raz Naftali , Cohen Ronald , Sweet Lawrence H , Colbert Lisa H , Josephson Richard , van Dulmen Manfred , Hughes Joel , Rosneck Jim , Gunstad John
Published: May 2013

Aims and objectives

To examine the independent association between executive function with instrumental activities of daily living and health behaviours in older adults with heart failure.

Background

Executive function is an important contributor to functional independence as it consists of cognitive processes needed for decision‐making, planning, organising and behavioural monitoring. Impairment in this domain is common in heart failure patients and associated with reduced performance of instrumental activities of daily living in many medical and neurological populations. However, the contribution of executive functions to functional independence and healthy lifestyle choices in heart failure patients has not been fully examined.

Design

Cross‐sectional analyses.

Methods

One hundred and seventy‐five heart failure patients completed a neuropsychological battery and echocardiogram. Participants also completed the Lawton–Brody Instrumental Activities of Daily Living Scale and reported current cigarette use.

Results

Hierarchical regressions revealed that reduced executive function was independently associated with worse instrumental activity of daily living performance with a specific association for decreased ability to manage medications. Partial correlations showed that executive dysfunction was associated with current cigarette use.

Conclusions

Our findings suggest that executive dysfunction is associated with poorer functional independence and contributes to unhealthy behaviours in heart failure. Future studies should examine whether heart failure patients benefit from formal organisation schema (i.e. pill organisers) to maintain independence.

Relevance to clinical practice

Screening of executive function in heart failure patients may provide key insight into their ability to perform daily tasks, including the management of treatment recommendations.
Including nurses in care models for older people with mild to moderate depression: an integrative review
Authors: Dreizler Jutta , Koppitz Andrea , Probst Sebastian , Mahrer‐Imhof Romy
Published: May 2013

Aims and objectives

The aim of this integrative literature review was twofold: (1) to investigate different collaborative programmes for older people with depression living at home with diverse access to care and (2) to describe conceptualisation of the nurses' role and interventions within these care models.

Background

One in four older people who visits a General Practitioner suffers from depression. Depression is a concern for 15% of all older home‐care service clients. Detecting and managing depression in older people is highlighted as a key role of nurses. A literature review has been conducted to investigate collaborative models of care, aimed at ensuring low‐threshold access to care and exploring the scope of nurse practice within these models.

Methods

Literature review comprising 14 studies and reviews.

Results

Three different collaborative care programmes (Collaborative Care Model, Community Mental Health Team and Psychogeriatric Assessment and Treatment in City Housing programme) were identified. In all programmes, the essential aspects were complex and multifaceted interventions, provided by a variety of healthcare professionals, but the access to care differed. All studies described the role of nurses differently and with wide variations.

Conclusions

Despite a broad scope of practice, nurses play a pivotal role within the different models of care. Nurses have to have the educational background and expertise in mental health issues to recognise depression and eventually be able to provide more comprehensive interventions to alleviate depression in older people.

Relevance to practice

Collaboration is needed to meet the needs of older people with depression. New forms of work divisions are pivotal to achieve this objective.
Caring for families of the terminally ill in Malaysia from palliative care nurses’ perspectives
Authors: Namasivayam Pathma , Lee Susan , O'Connor Margaret , Barnett Tony
Published: May 2013

Aims and objectives

To describe the process that nurses experienced in engaging with families in Malaysian palliative care settings and the challenges they faced.

Background

In palliative care settings, nurses and the terminally ill person's family members interact very closely with each other. It is important for nurses to work with families to ensure that the care of the terminally ill person is optimised.

Research design

A qualitative design using grounded theory methods was used to describe how nurses engaged with families and the challenges they faced.

Methods

Twenty‐two nurses from home care and inpatient palliative care settings across Malaysia participated in this study. Data were collected through seven interviews and eight focus group discussions conducted between 2007–2009.

Results

The main problem identified by nurses was the different expectations to patient care with families. The participants used the core process of Engaging with families to resolve these differences and implemented strategies described as Preparing families for palliative care, Modifying care and Staying engaged to promote greater consistency and quality of care. When participants were able to resolve their different expectations with families, these resulted in positive outcomes, described as Harmony. However, negative outcomes of participants not being able to resolve their different expectations with families were Disharmony.

Conclusions

This study highlights the importance of engaging and supporting families of the terminally ill as well as providing a guide that may be used by nurses and carers to better respond to families' needs and concerns.

Relevance to clinical practice

The study draws attention to the need for formal palliative care education, inclusive of family care, to enable nurses to provide the terminally ill person and their family effective and appropriate care.
JMS at 50: Trends over Time
Authors: Clark Timothy , Wright Mike , Iskoujina Zilia , Garnett Philip
Published: May 2013

We present an analysis of the articles published in the Journal of Management Studies since its inception to assess to what extent JMS has: maintained its leading international ranking; maintained its founding mission as a broad based management journal; and remained a broad based management journal compared to other general management journals. In terms of its impact factor and citations despite reaching a low point in 2001, we find that JMS today ranks higher than it has ever done throughout its 50‐year history. From our content analysis covering the life‐cycle of JMS, we find four areas have been the most frequently represented, although their relative importance varies between decades: Organizational Management/Behaviour, Strategy, Human Resource Management, and General Management, accounting for 67 per cent of articles published over the period. JMS has strengthened its international author distribution through the increase in authors from the EU especially; the period 2000–04 which saw the predominance of UK authors was an anomaly. There are marked differences between type of article and author country of origin. Our comparative analysis of the word networks between the journals JMS, AMJ, ASQ, and HRM shows that over each decade the papers in the first three normally form a single cluster, indicating that the words used in the papers in the different journals are similar, while papers from HRM often form an outlining group. Notably, in the early 2000s papers in JMS form a distinct cluster, with papers from HRM paralleling the anomaly identified in the content analysis. Overall, JMS has regained its distinctiveness as a broad‐based international management journal, not favouring any particular theoretical or empirical approach.
The Relationship Between Erectile Dysfunction and Open Urethroplasty: A Systematic Review and Meta-Analysis
Authors: Feng Chao , Xu Yue-Min , Barbagli Guido , Lazzeri Massimo , Tang Chen-ye , Fu Qiang , Sa Ying-Long
Published: May 2013

Introduction

Various urethroplasty techniques have been used to treat urethral stricture. Whether the patient erectile function is affected by this open surgery is still controversial.

Aim

The aim of this study is to determine the relationship between erectile function and open urethroplasty.

Methods

A systematic review of the literature was performed using Medline, Embase, the Web of Science, and the Cochrane Library databases through October 2012 to identify articles published in any language that examined the effect of open urethroplasty on the risk of erectile dysfunction (ED). This meta-analysis was conducted according to the guidelines for the meta-analysis of observational studies in epidemiology.

Main Outcome Measures

The incidence of ED after urethroplasty.

Results

This meta-analysis consisted of 23 cohort studies, which included 1,729 cases. No significant difference was noticed in patients with anterior urethral stricture before or after intervention (odds ratio [OR] = 0.86; 95% confidence interval [CI]: 0.52–1.40; P = 0.53). While statistical difference in the incidence of ED was revealed in patients before and after intervention for a posterior urethral (OR = 2.51; 95% CI: 1.82–3.45; P < 0.001), further comparisons demonstrated that most anterior urethroplasties did not have an obvious effect on patient erectile function. However, it seems that the incidence of ED was higher in the bulbar anastomosis group than in the oral graft urethroplasty group (OR = 0.32 95% CI: 0.11–0.93; P = 0.04). For the posterior urethroplasty, previous operative history did not show a strong relationship with ED. No statistically significant difference in the risk of ED was demonstrated comparing the posterior urethral reconstructive techniques included in this analysis.

Conclusion

The adverse effect of urethroplasty itself on erectile function is limited, as more patients recover erectile function after urethral reconstruction. For anterior urethroplasty, bulbar anastomosis might cause a slightly higher incidence of ED than other operations. For posterior urethroplasty, trauma might be the main cause of ED.
Performances of Police Legitimacy in Rio's Hyper Favela
Authors: Larkins Erika Robb
Published: May 2013

Rio de Janeiro is home to over one-thousand favelas (slums), the majority of which are controlled by armed drug traffickers engaged in a long-standing war with police. This article shows how state legitimacy is challenged by the everyday reality of dual power, postcolonial legacies of inequality and marginalization, and a porous culture of law. Drawing on ethnographic fieldwork in one of the largest favelas in the city, I argue that police actions revolve around the enactment of violent spectacle, performed by the Elite Special Forces, BOPE. The use of performative violence, however, rather than shoring up state control at the margins of city life, works instead to undermine police (and state) authority.
In Search of Moral Recognition? Policing and Eudaemonic Legitimacy in Ghana
Authors: Tankebe Justice
Published: May 2013

Ghana is widely considered as “a beacon of hope for democracy in Africa” (Gyimah-Boadi 2010, 137). Yet substantive democratic transformations of policing have stagnated mainly because the police continue to act as a handmaiden of the state and powerful elites. Consequently, the reliance on performance in crime control and order maintenance as the bedrock of colonial police legitimacy (as judged by colonial administrators) has survived unscathed. Anxieties about violent crime, mainly in urban areas, have accompanied the pursuit of neoliberal economics and politics. Having staked their legitimacy on performance, the police view these anxieties and doubts about their effectiveness as potentially de-legitimating. They have responded in a highly dramatic but violent fashion, including the extrajudicial killing of suspected violent offenders believed to be the cause of feelings of insecurity. This article examines the nature of this pathway to legitimacy.
Mutation design and strain background influence the phenotype of Escherichia coli luxS mutants
Authors: Haigh Richard , Kumar Brijesh , Sandrini Sara , Freestone Primrose
Published: May 2013

Previous analyses of luxS in Escherichia coli have used different strain backgrounds and design formats to produce the luxS mutation, resulting in luxS mutants with confusingly dissimilar phenotypes. This study therefore investigates the roles that strain background and mutational design strategy have upon the phenotype of the pathogenic E. coli luxS mutant. We inactivated luxS in three E. coli backgrounds: enteropathogenic E. coli E2348‐69, and enterohaemorrhagic strains Sakai and NCTC12900. To investigate the influence of mutational design strategy, four mutation formats were used: antibiotic resistance insertion methodologies as previously employed, using tetracycline and chloramphenicol resistance cassettes, and non‐polar strategies creating deletion and premature termination mutations. Our study showed that the E. coli luxS phenotype was markedly dependent on strain background: in some strains disruption of luxS caused significant metabolic stress or no stress at all. How the luxS mutation was constructed also shaped its phenotype: non‐polar mutants were very similar to wild type, while mutations made using the antibiotic insertion methodologies produced phenotypes defective in growth and virulence. Proteomic profiling of our luxS mutants showed only a few proteins were differentially expressed and those that were altered suggested a metabolic rather than communication role for the E. coli luxS gene product.
Cyanuric acid hydrolase: evolutionary innovation by structural concatenation
Authors: Peat Thomas S. , Balotra Sahil , Wilding Matthew , French Nigel G. , Briggs Lyndall J. , Panjikar Santosh , Cowieson Nathan , Newman Janet , Scott Colin
Published: May 2013

The cyanuric acid hydrolase, AtzD, is the founding member of a newly identified family of ring‐opening amidases. We report the first X‐ray structure for this family, which is a novel fold (termed the ‘Toblerone’ fold) that likely evolved via the concatenation of monomers of the trimeric YjgF superfamily and the acquisition of a metal binding site. Structures of AtzD with bound substrate (cyanuric acid) and inhibitors (phosphate, barbituric acid and melamine), along with mutagenesis studies, allowed the identification of the active site. The AtzD monomer, active site and substrate all possess threefold rotational symmetry, to the extent that the active site possesses three potential Ser–Lys catalytic dyads. A single catalytic dyad (Ser85–Lys42) is hypothesized, based on biochemical evidence and crystallographic data. A plausible catalytic mechanism based on these observations is also presented. A comparison with a homology model of the related barbiturase, Bar, was used to infer the active‐site residues responsible for substrate specificity, and the phylogeny of the 68 AtzD‐like enzymes in the database were analysed in light of this structure–function relationship.
PTS phosphorylation of Mga modulates regulon expression and virulence in the group A streptococcus
Authors: Hondorp Elise R. , Hou Sherry C. , Hause Lara L. , Gera Kanika , Lee Ching‐En , McIver Kevin S.
Published: May 2013

The ability of a bacterial pathogen to monitor available carbon sources in host tissues provides a clear fitness advantage. In the group A streptococcus (GAS), the virulence regulator Mga contains homology to phosphotransferase system (PTS) regulatory domains (PRDs) found in sugar operon regulators. Here we show that Mga was phosphorylated in vitro by the PTS components EI/HPr at conserved PRD histidines. A ΔptsI (EI‐deficient) GAS mutant exhibited decreased Mga activity. However, PTS‐mediated phosphorylation inhibited Mga‐dependent transcription of emm in vitro. Using alanine (unphosphorylated) and aspartate (phosphomimetic) mutations of PRD histidines, we establish that a doubly phosphorylated PRD1 phosphomimetic (D/DMga4) is completely inactive in vivo, shutting down expression of the Mga regulon. Although D/DMga4 is still able to bind DNA in vitro, homo‐multimerization of Mga is disrupted and the protein is unable to activate transcription. PTS‐mediated regulation of Mga activity appears to be important for pathogenesis, as bacteria expressing either non‐phosphorylated (A/A) or phosphomimetic (D/D) PRD1 Mga mutants were attenuated in a model of GAS invasive skin disease. Thus, PTS‐mediated phosphorylation of Mga may allow the bacteria to modulate virulence gene expression in response to carbohydrate status. Furthermore, PRD‐containing virulence regulators (PCVRs) appear to be widespread in Gram‐positive pathogens.
The sensor kinase KdpD of Escherichia coli senses external K+
Authors: Laermann Vera , Ćudić Emina , Kipschull Kerstin , Zimmann Petra , Altendorf Karlheinz
Published: May 2013

The Kdp system of Escherichia coli is composed of the high‐affinity K+ transporter KdpFABC and the two regulatory proteins KdpD (sensor kinase) and KdpE (response regulator), which constitute a typical two‐component system. The kdpFABC operon is induced under K+‐limiting conditions and, to a lesser extent, under high osmolality in the medium. In search for the stimulus sensed by KdpD, we studied the inhibitory effect of extracellular K+ on the Kdp system at pH 6.0, which is masked by unspecific K+ transport at higher pH values. Based on KdpD derivatives carrying single aspartate replacements in the periplasmic loops which are part of the input domain, we concluded that the inhibition of the Kdp system at extracellular K+ concentrations above 5 mM is mediated via KdpD/KdpE and not due to inhibition of the K+‐transporting KdpFABC complex. Furthermore, time‐course analyses of kdpFABC expression revealed that a decline in the extracellular K+ concentration efficiently stimulates KdpD/KdpE‐mediated signal transduction. In this report we provide evidence that the extracellular K+ concentration serves as one of the stimuli sensed by KdpD.
Paralogous chemoreceptors mediate chemotaxis towards protein amino acids and the non‐protein amino acid gamma‐aminobutyrate (GABA)
Authors: Rico‐Jiménez Miriam , Muñoz‐Martínez Francisco , García‐Fontana Cristina , Fernandez Matilde , Morel Bertrand , Ortega Álvaro , Ramos Juan Luis , Krell Tino
Published: May 2013

The paralogous receptors PctA, PctB and PctC of Pseudomonas aeruginosa were reported to mediate chemotaxis to amino acids, intermediates of amino acid metabolism and chlorinated hydrocarbons. We show that the recombinant ligand binding regions (LBRs) of PctA, PctB and PctC bind 17, 5 and 2 l‐amino acids respectively. In addition, PctC‐LBR recognized GABA but not any other structurally related compound. l‐Gln, one of the three amino acids that is not recognized by PctA‐LBR, was the most tightly binding ligand to PctB suggesting that PctB has evolved to mediate chemotaxis primarily towards l‐Gln. Bacteria were efficiently attracted to l‐Gln and GABA, but mutation of pctB and pctC, respectively, abolished chemoattraction. The physiological relevance of taxis towards GABA is proposed to reside in an interaction with plants. LBRs were predicted to adopt double PDC (PhoQ/DcuS/CitA) like structures and site‐directed mutagenesis studies showed that ligands bind to the membrane‐distal module. Analytical ultracentrifugation studies have shown that PctA‐LBR and PctB‐LBR are monomeric in the absence and presence of ligands, which is in contrast to the enterobacterial receptors that require sensor domain dimers for ligand recognition.
The role of zinc in the interplay between pathogenic streptococci and their hosts
Authors: Shafeeq Sulman , Kuipers Oscar P. , Kloosterman Tomas G.
Published: May 2013

Recent studies on pathogenic streptococci have revealed that zinc is a pivotal metal ion in their interaction with the host. In these streptococci, systems exist that ensure optimal use of zinc from the surrounding milieu, as well as export of zinc when concentrations exceed tolerance levels. Zinc uptake is of crucial importance for the virulence of streptococci, whereas elevated zinc levels induced in the host during infection are detrimental for these pathogens. The expression or activity of a number of putative surface proteins and virulence factors depends on zinc. Moreover, several metal sensor proteins that mediate the transcriptional response to zinc in streptococci have recently been characterized. A number of components of zinc‐ and other metal ion‐acquisition systems are suitable as protective antigens and may be future targets for the development of new vaccines, thus providing opportunities for the development of novel therapies. This review will discuss the recent advancements in the important field of metal ion biology in relation to the virulence of pathogenic streptococci, with a central focus on zinc homeostasis in Streptococcus pneumoniae.
Cadential Intervention inShostakovich's Piano Trio inEminor, Op. 67
Authors: Fankhauser Gabriel
Published: May 2013

Insertions between the structural dominant and tonic of underlying perfect cadences delay and intensify progressions of harmony, voice leading and hypermetre. More disruptive than other evaded cadences, these cadential interventions ultimately still serve to unify the music through motivic development. Brief analysis of excerpts from the works ofJ.S.Bach andHaydn demonstrates the traditional use of cadential intervention and prepares for the analysis of an idiomatic approach byShostakovich. His Prelude inC♯ minor, Op. 34 No. 10, and Second Piano Trio, Op. 67, contain extraordinary cadential interventions that seem to break continuity, on the one hand, yet serve vital unifying roles in the larger context of each piece, on the other. Since both structural and hermeneutical meaning in the Trio hinges on interpretation of its tonal closure, the cadential intervention at its conclusion receives special attention. Modified Schenkerian analysis invites an alternative approach, showing how an underlying complete tonal structure may substantiate a complete narrative.
In vitro antibacterial activity and physicochemical properties of a crude methanol extract of the larvae of the blow fly Lucilia cuprina
Authors: TEH C. H. , NAZNI W. A. , LEE H. L. , FAIRUZ A. , TAN S. B. , SOFIAN‐AZIRUN M.
Published: May 2013

The emergence of multidrug‐resistant bacterial strains has prompted the reintroduction of maggot therapy in the treatment of chronic, infected wounds. Many previous studies have demonstrated the potent antibacterial activity of larval excretions/secretions of the blowfly Lucilia sericata (Meigen) (Diptera:Calliphoridae) against bacteria. However, the antibacterial activity of its sibling species, Lucilia cuprina (Wiedemann) (Diptera:Calliphoridae) against a wide range of pathogenic bacteria has never been determined. The aim of this study was to develop a new procedure to produce whole body extract of larvae of L. cuprina via methanol extraction as well as to demonstrate the in vitro antibacterial activity of this extract against seven selected wound pathogens (Staphylococcus aureus, methicillin‐resistant S. aureus, S. epidermidis, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli). The turbidimetric assay demonstrated that L. cuprina larval extract was significantly potent against all bacteria tested (P < 0.001). Additionally, colony‐forming unit (CFU), agar well diffusion and minimum inhibitory concentration assays have confirmed the apparent potency of larval extract against P. aeruginosa. The reconstituted larval extract was highly robust and thermally stable. These observations substantiated the feasibility of the methanol extraction method in the production of larval extract.
Apples and oranges: a comparison of costing methods for obesity
Authors: Bierl M. , Marsh T. , Webber L. , Brown M. , McPherson K. , Rtveladze K.
Published: May 2013

Obesity has escalated to epidemic proportions over the past 30 years resulting in increased disease burden and healthcare costs. The aim of this paper was to analyse different costing methods for obesity. Several databases have been searched to identify eligible literature estimating obesity cost. These were categorized into databases, patient‐attributable fraction (PAF) and modelling studies. Studies from the United States were used to explore effects of study designs on cost outcomes. Our results show that cost outcomes are largely affected by underlying study designs, such as population size, age, cost categories (medical expenditure vs. total costs), length of the data collection and body mass index cut‐offs. Three study types are likely to have an impact on reported costs, with modelling studies providing the most conservative estimates. Database studies can help to increase the overall awareness of the economic burden of obesity. PAF studies can make the obesity disease more tangible by drawing connections to diseases. Decision makers need to be aware of the different purposes and weaknesses of the studies when interpreting cost outcomes. Further research is needed to refine the existing methods and provide high‐quality data accounting for the complexity of the disease.
The Comparison of Two Vertical Outsourcing Structures under Push and Pull Contracts
Authors: Wang Yulan , Niu Baozhuang , Guo Pengfei
Published: May 2013

In a three‐tier supply chain comprising an original equipment manufacturer (OEM), a contract manufacturer (CM), and a supplier, there exist two typical outsourcing structures: control and delegation. Under the control structure, the OEM contracts with the CM and the supplier respectively. Under the delegation structure, the OEM contracts with the CM only and the CM subcontracts with the supplier. We compare the two outsourcing structures under a push contract (whereby orders are placed before demand is realized) and a pull contract (whereby orders are placed after demand is realized). For all combinations of outsourcing structures and contracts, we derive the corresponding equilibrium wholesale prices, order quantities, and capacities. We find that the equilibrium production quantity is higher under control than under delegation for the push contract whereas the reverse holds for the pull contract. Both the OEM and the CM prefer control over delegation under the push contract. However, under the pull contract, the OEM prefers control over delegation whereas the CM and the supplier prefer delegation over control. We also show that for a given outsourcing structure, the OEM prefers the pull contract over the push contract. In extending our settings to a general two‐wholesale‐price (TWP) contract, we find that when wholesale prices are endogenized decision variables, the TWP contract under our setting degenerates to either a push or a pull contract.
Supply Disruptions, Heterogeneous Beliefs, and Production Efficiencies
Authors: Chen Ying‐Ju
Published: May 2013

Recent years have witnessed the pervasive supply disruptions and their impacts on supply chain performance. In this study, we investigate the optimal procurement design with supply disruptions and heterogeneous beliefs between the buyer and the supplier. We examine the impact of information asymmetry on the supplier's belief, the control right of the backup production, and the verifiability of supply disruption. The belief heterogeneity creates speculative gains and losses because the buyer and the supplier hold different estimates of the disruption probability. We demonstrate that the buyer's incentive to exploit this belief heterogeneity leads to real production inefficiencies in different scenarios. The production efficiency is not necessarily improved with more transparent information. Moreover, a very pessimistic supplier may have no incentive to invest in improving the reliability even if this is costless, and the supplier may produce more when the expected production cost becomes higher. When the buyer sees some value in using the supplier's estimate to update his own belief, we find that the main results hold unless the buyer completely abandons his belief.