bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological rather than geographical isolation dominates Quaternary formation of Mediterranean Cistus species
Authors: FERNÁNDEZ‐MAZUECOS M. , VARGAS P.
Published: March 2010

The lack of a comparative approach makes it impossible to determine the main factors influencing colonization and evolution in plants. Here we conducted the first comparative study of a characteristic Mediterranean lineage (white‐flowered Cistus) taking advantage of its well‐known phylogenetic relationships. A two‐scale approach was applied to address the hypothesis of higher levels of isolation in mountain than in lowland species. First, a time‐calibrated phylogeny using plastid sequences of Cistaceae suggested that the origin of Cistus species postdated both the refilling of the Mediterranean Sea (5.59–5.33 Ma) and the onset of the Mediterranean climate (3.2 Ma). Two hundred and sixty‐three additional, plastid sequences from 111 populations showed different numbers of haplotypes in C. laurifolius (7), C. monspeliensis (2) and C. salviifolius (7). Although haplotype sharing among disjunct populations was observed in all species, phylogeographic analyses revealed haplotype lineages exclusive to Europe or Africa only in the mountain species (C. laurifolius). Isolation by either geographical distance or sea barriers was not significantly supported for the lowland species (C. monspeliensis; C. ladanifer from a previous study). The same is true for the less habitat‐specific species of the lineage (C. salviifolius). Comparative phylogeography of the Cistus species leads us to interpret a general pattern of active colonization surpassing Mediterranean barriers. In contrast, ecological conditions (precipitation, temperature, soils) appear to have determined the distribution of the Cistus species of Mediterranean mountains. This study further provides molecular evidence for multiple colonization patterns in the course of successful adaptation of Cistus species to Mediterranean habitats.
A dominant‐negative needle mutant blocks type III secretion of early but not late substrates in Yersinia
Authors: Davis Alison J. , De Jesús Díaz Dennise A. , Mecsas Joan
Published: March 2010

Yersinia pseudotuberculosis uses a type III secretion system (T3SS) to deliver effectors into host cells. A key component of the T3SS is the needle, which is a hollow tube on the bacterial surface through which effectors are secreted, composed of the YscF protein. To study needle assembly, we performed a screen for dominant‐negative yscF alleles that prevented effector secretion in the presence of wild‐type (WT) YscF. One allele, yscF‐L54V, prevents WT YscF secretion and needle assembly, although purified YscF‐L54V polymerizes in vitro. YscF‐L54V binds to its chaperones YscE and YscG, and the YscF‐L54V–EG complex targets to the T3SS ATPase, YscN. We propose that YscF‐L54V stalls at a binding site in the needle assembly pathway following its release from the chaperones, which blocks the secretion of WT YscF and other early substrates required for building a needle. Interestingly, YscF‐L54V does not affect the activity of pre‐assembled actively secreting machines, indicating that a factor and/or binding site required for YscF secretion is absent from T3SS machines already engaged in effector secretion. Thus, substrate switching may involve the removal of an early substrate‐specific binding site as a mechanism to exclude early substrates from Yop‐secreting machines.
NAD+ auxotrophy is bacteriocidal for the tubercle bacilli
Authors: Vilchèze Catherine , Weinrick Brian , Wong Ka‐Wing , Chen Bing , Jacobs, Jr William R.
Published: March 2010

The human tubercle bacillus Mycobacterium tuberculosis can synthesize NAD+ using the de novo biosynthesis pathway or the salvage pathway. The salvage pathway of the bovine tubercle bacillus Mycobacterium bovis was reported defective due to a mutation in the nicotinamidase PncA. This defect prevents nicotinic acid secretion, which is the basis for the niacin test that clinically distinguishes M. bovis from M. tuberculosis. Surprisingly, we found that the NAD+de novo biosynthesis pathway (nadABC) can be deleted from M. bovis, demonstrating a functioning salvage pathway. M. bovisΔnadABC fails to grow in mice, whereas M. tuberculosisΔnadABC grows normally in mice, suggesting that M. tuberculosis can acquire nicotinamide from its host. The introduction of M. tuberculosis pncA into M. bovisΔnadABC is sufficient to fully restore growth in a mouse, proving that the functional salvage pathway enables nicotinamide acquisition by the tubercle bacilli. This study demonstrates that NAD+ starvation is a cidal event in the tubercle bacilli and confirms that enzymes common to the de novo and salvage pathways may be good drug targets.
Regulation of phosphate uptake via Pst transporters in Halobacterium salinarum R1
Authors: Furtwängler Katarina , Tarasov Valery , Wende Andy , Schwarz Christoph , Oesterhelt Dieter
Published: March 2010

The genome of the archaeon Halobacterium salinarum contains two copies of the pst (phosphate‐specific transport) operon, the genes of which are related to well‐studied bacterial homologues. Both operons (pst1 and pst2) were shown to be polycistronic and, when under Pi‐limited conditions, transcription initiated 1 bp upstream of the translational starts. Under Pi saturation, the pst1 operon utilized an additional transcription start site 59 bp upstream of the first one. The leaderless pst1 transcript was found to be more efficiently translated than the leadered transcript. Promoter strengths differed significantly between the two operons and when Pi levels changed. The basal pst1 promoter activity in Pi‐saturated conditions was minimal while the pst2 promoter was active. In contrast, phosphate limitation induced the pst1 operon threefold more than the pst2 operon. We identified basic and phosphate‐dependent cis‐acting elements in both promoters. Phosphate‐uptake assays conducted with several Pst1 and Pst2 mutant strains revealed differences in the substrate affinities between the two transporters and also suggested that the Pi‐binding proteins PstS1 and PstS2 can interact with either of the two permease subunits of the transporters. The tactic behaviour of wild type and pst‐deletion strains showed that the Pst1 transporter plays an important role for phosphate‐directed chemotaxis.
Fitness correlates with the extent of cheating in a bacterium
Authors: JIRICNY N. , DIGGLE S. P. , WEST S. A. , EVANS B. A. , BALLANTYNE G. , ROSS‐GILLESPIE A. , GRIFFIN A. S.
Published: March 2010

There is growing awareness of the importance of cooperative behaviours in microbial communities. Empirical support for this insight comes from experiments using mutant strains, termed ‘cheats’, which exploit the cooperative behaviour of wild‐type strains. However, little detailed work has gone into characterising the competitive dynamics of cooperative and cheating strains. We test three specific predictions about the fitness consequences of cheating to different extents by examining the production of the iron‐scavenging siderophore molecule, pyoverdin, in the bacterium Pseudomonas aeruginosa. We create a collection of mutants that differ in the amount of pyoverdin that they produce (from 1% to 96% of the production of paired wild types) and demonstrate that these production levels correlate with both gene activity and the ability to bind iron. Across these mutants, we found that (1) when grown in a mixed culture with a cooperative wild‐type strain, the relative fitness of a mutant is negatively correlated with the amount of pyoverdin that it produces; (2) the absolute and relative fitness of the wild‐type strain in the mixed culture is positively correlated with the amount of pyoverdin that the mutant produces; and (3) when grown in a monoculture, the absolute fitness of the mutant is positively correlated with the amount of pyoverdin that it produces. Overall, we demonstrate that cooperative pyoverdin production is exploitable and illustrate how variation in a social behaviour determines fitness differently, depending on the social environment.
Give ‘til it hurts: trade‐offs between immunity and male reproductive effort in the decorated cricket, Gryllodes sigillatus
Authors: GERSHMAN S. N. , BARNETT C. A. , PETTINGER A. M. , WEDDLE C. B. , HUNT J. , SAKALUK S. K.
Published: March 2010

Trade‐offs between life‐history variables can be manifested at either the phenotypic or genetic level, with vastly different evolutionary consequences. Here, we examined whether male decorated crickets (Gryllodes sigillatus) from eight inbred lines and the outbred founder population from which they were derived, trade‐off immune effort [lytic activity, phenoloxidase (PO) activity or encapsulation] to produce spermatophylaxes: costly nuptial food gifts essential for successful sperm transfer. Canonical correlation analysis of the outbred population revealed a trade‐off between spermatophylax mass and lytic activity. Analysis of our inbred lines, however, revealed that although PO activity, encapsulation, body mass, spermatophylax mass and ampulla (sperm capsule) mass were all highly heritable, lytic activity was not, and there was, therefore, no negative genetic correlation between lytic activity and spermatophylax mass. Thus, males showed a phenotypic but not a genetic trade‐off between spermatophylax mass and lytic activity, suggesting that this trade‐off is mediated largely by environmental factors.
Psychological and behavioural impacts of the 2008 China earthquake on blood donors
Authors: Tian F. , Wang J. , Huang Y. , Guo X. , Yun Z. , Yang T. , Nelson K. , Schreiber G. B. , Ness P. , Shan H.
Published: March 2010

Background and Objectives  On May 12, 2008, a severe earthquake hit Sichuan province in China. A post‐earthquake survey was conducted to study the earthquake’s effect on blood donor behaviour and stress at three blood centres at varying distances from the epicentre.

Materials and Methods  A questionnaire was developed to assess donor post‐traumatic stress disorders (PTSD) and attitudes toward giving blood. Responses were compared by centre and donor characteristics using multivariate logistic regression techniques.

Results  Of all 17 456 donors, the overall prevalence of PTSD was 13·2%. Donors who knew someone killed or injured by the earthquake were 2·1 times more likely to have PTSD than others (95% CI: 1·8–2·4). 85·2% of donors cited the earthquake as their reason for donating. 16·1% of donors felt it acceptable to be less honest about one’s health history in an emergency. After adjusting for PTSD, geographic and demographic characteristics, the donors knowing someone killed or injured by the earthquake were 1·4 times (95% CI: 1·2–1·7) more likely to cite the earthquake as reason for donating, and 1·8 times (95% CI: 1·5–2·1) more likely to accept being less honest about one’s health history in case of national emergency.

Conclusions  The psychological and behavioural impacts of the earthquake on blood donors extended far from the epicentre. After a disaster, it is important to emphasize that donors must be truthful on the donor questionnaire as some donors appear willing to be less than honest when they perceive an increased need for blood products.
Construct validity of the Comprehensive Developmental Inventory for Infants and Toddlers
Authors: Hwang Ai‐Wen , Weng Li‐Jen , Liao Hua‐Fang
Published: March 2010

Background: The aim of this study was to investigate the construct validity of the diagnostic test, the Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT).

Methods: A total of 1085 children in four age groups (infant, 1‐year‐old, 2‐year‐old, preschool age) were enrolled. The Developmental Quotient of each subdomain of the five CDIIT subtests (Cognition, Language, Motor, Social, and Self‐help) was used as the basic unit for factor analysis with the iterative principle factor method and promax rotation.

Results: The two‐factor solution in two younger age groups and 2‐ or 3‐factor solutions in the 2‐year‐old and preschool groups provided superior factor structure in terms of interpretability and compatibility with existing child development theories.

Conclusion: Although five constructs were proposed in the original manual of CDIIT, two to three constructs were revealed in this empirical study.
Impact of sustained neuromuscular blockade on outcome of mechanically ventilated children
Authors: Da Silva Paulo S.L. , Neto Henrique M. , De Aguiar Vânia E. , Lopes Jr Emílio , De Carvalho Werther B.
Published: March 2010

Background:  Neuromuscular blocking agents (NMBA) are commonly administered to critically ill children in pediatric intensive care units (PICU) in the USA and Europe. Although NMBA are frequently used in PICU patients, their role in the PICU setting has not yet been clearly defined. The aim of this study was to describe the sustained administration of NMBA and its impact on outcome of PICU patients.

Methods:  A 3‐year retrospective cohort study was conducted to compare mechanically‐ventilated patients who received NMBA for at least 12 h with patients who did not (control group).

Results:  A total of 317 consecutive patients were ventilated over 3473 days. Patients were similar in age, weight and severity scores. Thirty‐four children (10.7%) received NMBA. Compared with controls, the neuromuscular blockade (NMB) group had a longer duration of mechanical ventilation (13.7 vs 5.5 days, P= 0.000), longer PICU stay (20 vs 11 days, P= 0.000) and increased occurrence of ventilator‐associated pneumonia (6.6 vs 4.1/1000 ventilator days, P= 0.010). The NMB use was not associated with higher mortality (8.8% vs 17.6%, P= 0.287) or longer hospital stay (30.5 vs 23 days, P= 0.117).

Conclusion:  Although the use of NMBA was not associated with greater mortality, we found that sustained use of NMBA is associated with prolonged mechanical ventilation, longer PICU stay and higher incidence of ventilator‐associated pneumonia when compared with controls. Larger studies are necessary to confirm these findings.
Evolution in pediatric health care
Authors: Genuis Stephen J.
Published: March 2010

Background:  There is disturbing evidence of escalating chronic disease among children – a phenomenon that is extracting a heavy toll from individuals, families, and health‐care systems.

Methods:  This review was prepared by assessing medical and scientific literature available from Medline, as well as by reviewing numerous books, conference proceedings, and government publications.

Results:  Knowledge translation in medical science, the process whereby new research is incorporated into clinical practice, remains lethargic. Nutritional and environmental factors have recently been recognized as common determinants of modern illness, and various diagnostic techniques in molecular medicine are now available to facilitate diagnosis of disease etiology.

Conclusions:  A re‐evaluation of the current pediatric clinical paradigm is required in light of emerging research from fields such as epigenetics, molecular medicine and environmental health. Education about these branches of medical science should be integrated into pediatric medical education, and important research information from these disciplines should be incorporated into public health care and clinical practice relating to children.
Eleven‐year study of causes of neonatal bacterial meningitis in Ahvaz, Iran
Authors: Aletayeb Mohammad Hasan , Ahmad Farajzadeh Sheikh , Masood Dehdashtian
Published: March 2010

Background:  Bacterial meningitis is a devastating infection with a high mortality rate, especially in neonates. The aim of this study was to determine the causative agents that cause bacterial meningitis in Khuzestan province in the south‐western region of Iran.

Methods:  A descriptive, cross‐sectional study was carried out from 1997 to 2007 at the neonatal ward of a university teaching hospital (Emam Khomeini hospital) in Ahvaz. All infants younger than 29 days old who suffered from meningitis were included. Laboratory tests included Gram stain, culture, and biochemical tests. Cases were defined as meningitis if the cerebrospinal fluid culture was positive.

Results:  Based on cerebrospinal fluid culture, 31 infants were identified as having bacterial meningitis. Eleven (35.5%) of these cases were caused by Klebsiella pneumoniae, nine (29%) were caused by Enterobacter spp., three (9.6%) were caused by Escherichia coli, three (9.6%) were caused by Enterococcus spp., two (6.4%) were caused by Acinetobacter, and one case each (3.2%) was caused by Staphylococcus aureus, Pseudomonas aeruginosa and nontypeable Haemophilus influenzae. The male‐to‐female ratio was 2 : 1 (67.7% were male). The birthweights of 20 (64.5%) patients were under 2500 g and 11 (35.4%) patients had normal birthweights. Thirteen (42%) were early‐onset cases and 18 (58%) were late‐onset cases. More than half of the cases (54.8%) acquired the infection from the hospital. Blood cultures were positive for 18 (58%) patients. Thirty‐two percent of cases died in spite of treatment.

Conclusions:  Klebsiella pneumoniae and Enterobacter spp. were the two main causative agents that caused neonatal bacterial meningitis, and nosocomial meningitis was the most common type in our ward.
Lentivirus‐mediated gene transfer of interleukin 10 to the ovine and human cornea
Authors: Parker Douglas G , Coster Douglas J , Brereton Helen M , Hart Prue H , Koldej Rachel , Anson Donald S , Williams Keryn A
Published: March 2010

Abstract

Background:  Gene transfer to a donor cornea ex vivo can modulate corneal graft failure in experimental animal models. We compared a lentiviral vector (LV) carrying the transgene ovine interleukin 10 (IL10) with a comparable adenoviral vector (Ad) for its ability to transduce ovine and human corneas and to modulate ovine corneal allograft survival.

Methods:  The LV carrying the ovine IL10 gene was used to transduce ovine and human corneas in vitro. LV‐mediated gene expression in corneal endothelium was assessed by real‐time quantitative reverse‐transcriptase polymerase chain reaction, at varying doses and duration of transduction. The effect of ex vivo transduction of the donor cornea with LV‐SV40‐IL10 was assessed following orthotopic corneal transplantation in outbred sheep.

Results:  Expression of IL10 mRNA in Ad‐CMV‐IL10‐transduced ovine corneas was 103‐fold higher than in LV‐SV40‐IL10‐transduced corneas (P < 0.0001), and 107‐fold higher than in non‐transduced controls. IL10 was secreted rapidly from Ad‐CMV‐IL10‐transduced, organ‐cultured corneas, peaking at 13–15 days. IL10 secreted from LV‐SV40‐IL10‐transduced corneas increased 20‐fold compared with controls, but had not reached a plateau at 15 days. Gene expression driven by LV‐SV40‐IL10 varied with vector dose and transduction time, but was less than with Ad‐CMV‐IL10 at both mRNA and protein levels. Gene expression driven by LV‐SV40‐IL10 was faster in the human cornea than the ovine cornea. Corneal allograft survival was prolonged by a median of 7 days in the LV‐SV40‐IL10‐treated recipients, compared with the control group (P = 0.026).

Conclusion:  Although lentiviral vectors show some promise for corneal gene therapy, they are less efficient than adenoviral vectors.
Testing a facilitation model for ecosystem restoration: Does tree planting restore ground layer species in a grassy woodland?
Authors: NICHOLS PETER W. B. , MORRIS E. CHARLES , KEITH DAVID A.
Published: March 2010

Planning for the restoration of degraded ecosystems has a strong basis in facilitation successional theory, which, as applied in restoration practice, states that planting of structurally dominant tree species will assist the entry of other native species into a restored community. In Australia, tree planting has been widely applied in restoration of grassy woodland ecosystems. Trees have been postulated to reduce the cover and diversity of weed species, thus facilitating recolonization of native woodland species (indirect facilitation). The expected outcomes of this process include reduced species richness and abundance of exotic plant species and increased species richness and abundance/dominance of natives in areas beneath tree canopies, with these trends strengthening with time. To assess whether this was occurring, we carried out a comparative analysis of species assemblages found underneath and outside of planted tree canopies in sites replanted with juvenile canopy tree species 3–5 or 8–10 years previously. We sampled revegetated stands of Cumberland Plain Woodland, an endangered ecological community in Western Sydney, Australia. We found that neither the number nor abundance of native ground layer species beneath canopies increased as a result of trees being planted at sites of both ages. Where seed is limited, we predicted an increase in abundance of existing native species under planted tree canopies. On this point, the results were mixed and showed some natives with an increased abundance while others decreased. Exotic species richness showed the reverse of the expected pattern, being greater under tree canopies. These findings lend no support to the theory of indirect facilitation. We conclude that simple facilitation models may be inadequate to support planning of grassy woodland restoration and that those models incorporating successional time lags and restoration barriers are likely to be more informative about the development of communities initiated by tree planting.
Mammal responses to matrix development intensity
Authors: BRADY MEGAN J. , MCALPINE CLIVE A. , MILLER CRAIG J. , POSSINGHAM HUGH P. , BAXTER GREG S.
Published: March 2010

The landscape matrix is increasingly being recognized as important to biodiversity conservation. The nature of the matrix impacts the persistence of species in human‐modified landscapes through its pervasive influence on adjacent habitat and through the habitat value of the matrix itself. However, previous studies have not isolated the effects of the matrix from the effects of other aspects of landscape modification, such as habitat loss and fragmentation, and much remains to be understood about the independent impact of the matrix on wildlife. We investigated the effects of the matrix on mammal abundance and landscape use in south‐east Queensland, Australia. Mammals were surveyed in patch ‘core’, patch ‘edge’ and ‘matrix’ landscape elements along a rural–suburban gradient of matrix development intensity quantified by a weighted road‐length metric, which was significantly correlated with housing density, while controlling for potentially confounding patch and landscape attributes. Response to increasing matrix development intensity was highly species‐specific. Several native species declined in abundance; however, others were more resilient to moderate levels of matrix intensity, one species increased in abundance, and at least one species appeared unaffected by matrix intensity. Native species richness peaked at moderate levels of matrix development intensity. Exotic species richness and feral predators increased with matrix intensity and were negatively correlated with native species. Species response to matrix intensity appeared related to their use of edge or matrix habitat. An ability to use the matrix per se, however, may not translate into an ability to persist in a landscape where development substantially reduces the habitat or movement value of the matrix.
Growth and survivorship as proximate causes of sexual size dimorphism in peninsula dragon lizards Ctenophorus fionni
Authors: JOHNSTON GREG
Published: March 2010

Males and females differ in body size in many animals, but the direction and extent of this sexual size dimorphism (SSD) varies widely. Males are larger than females in most lizards of the iguanian clade, which includes dragon lizards (Agamidae). I tested whether the male larger pattern of SSD in the peninsula dragon lizard, Ctenophorus fionni, is a result of sexual selection for large male size or relatively higher mortality among females. Data on growth and survivorship were collected from wild lizards during 1991–1994. The likelihood of differential predation between males and females was assessed by exposing pairs of male and female lizards to a predator in captivity, and by comparing the frequency of tail damage in wild‐caught males and females. Male and female C. fionni grew at the same rate, but males grew for longer than females and reached a larger asymptotic size (87 mm vs. 78 mm). Large males were under‐represented in the population because they suffered higher mortality than females. Predation may account for some of this male‐biased mortality. The male‐biased SSD in C. fionni resulted from differences in growth pattern between the sexes. The male‐biased SSD was not the result of proximate factors reducing female body size. Indeed SSD in this species remained male‐biased despite high mortality among large males. SSD in C. fionni is consistent with the ultimate explanation of sexual selection for large body size in males.
The recovery of urinary continence after radical retropubic prostatectomy: a randomized trial comparing the effect of physiotherapist‐guided pelvic floor muscle exercises with guidance by an instruction folder only
Authors: Dubbelman Yvette , Groen Jan , Wildhagen Mark , Rikken Berend , Bosch Ruud
Published: March 2010

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVE

To compare the effect on the recovery of incontinence after retropubic radical prostatectomy (RRP) of intensive physiotherapist‐guided pelvic floor muscle exercises (PG‐PFME) in addition to an information folder, with PFME explained to patients by an information folder only (F‐PFME), and to determine independent predictors of failure to regain continence after RRP.

PATIENTS AND METHODS

We postulated that a 10% increase in the proportion of men who regained continence at 6 months with PG‐PFME compared with men treated with F‐PFME only would constitute a clinically relevant effect. To show statistical significance of this difference with a power of 80%, 96 men should be randomized to each of the two arms. One day before operation, all patients received verbal instruction and an information folder on PFME. Patients randomized to the F‐PFME arm received no further physiotherapist guidance, whereas those in the PG‐PFME arm received a maximum of nine sessions with the physiotherapist. The men underwent a 1‐h pad‐test at 1, 12 and 26 weeks, and a 24‐h pad‐test at 1, 4, 8, 12 and 26 weeks after catheter removal. We defined ‘continence’ as urine loss of <1 g at the 1‐h and <4 g at the 24‐h pad‐test.

RESULTS

During the 2‐year recruitment period, the number of patients randomized fell short of the target determined by the sample size calculation, because of limitations of resources and unexpected changes in treatment preferences. Despite this, we analysed the data. Of the 82 randomized patients, 70 completed the study. Of these, 34 and 36 men had been assigned to the PG‐PFME and the F‐PFME group, respectively. At 6 months after RRP, 10 (30%) and nine (27%) men were completely dry on both the 1‐h and 24‐h pad‐test in the PG‐PFME and the F‐PFME group, respectively (difference not significant). In a multivariate analysis the amount of urine loss at 1 week after catheter removal seemed to be an independent prognostic factor for failure to regain continence.

CONCLUSION

PG‐PFME seems to have no beneficial effect on the recovery of continence within the first 6 months after RRP, over an instruction folder‐guided approach. However, due to under‐powering there is a high risk of type II error. Nevertheless, these findings add to the knowledge base for availability in meta‐analyses and can serve as a starting point for the design of new randomized studies.
Total urethral construction with the radial artery‐based forearm free flap in the transsexual
Authors: Garaffa Giulio , Ralph David J. , Christopher Nim
Published: March 2010

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

OBJECTIVE

To report our experience of using a radial artery‐based forearm free flap urethroplasty (RAFFFU) inside a pre‐fashioned pedicled pubic phalloplasty for female‐to‐male gender reassignment.

PATIENTS AND METHODS

A neourethra based on the RAFFF was incorporated into a previously constructed phalloplasty in 27 patients. Surgical outcome, patients’ satisfaction and voiding sensation of the neourethra were subjectively and prospectively assessed by direct questioning during the follow‐up.

RESULTS

After a median follow‐up of 9.2 months, all patients who completed the two stages of the procedure were able to void from the tip of the phallus while standing. Donor‐site morbidity was minimal, with all patients reporting a complete recovery of forearm sensation and mobility. The overall satisfaction rate was 92%.

CONCLUSIONS

The RAFFFU is the best technique of total urethral construction in female‐to‐male transsexuals who opt not to undergo a RAFFF phalloplasty.
Failure of bacille Calmette‐Guérin in patients with high risk non‐muscle‐invasive bladder cancer unsuitable for radical cystectomy: an update of available treatment options
Authors: Yates David R. , Rouprêt Morgan
Published: March 2010

Although the accepted standard upon failing intravesical bacille Calmette‐Guérin (BCG) in patients with high‐risk non‐muscle‐invasive bladder cancer (NMIBC) is radical cystectomy, there are some patients for whom this is not an option. We critically reviewed previous reports on the treatment possibilities available in such a clinical scenario. The options available can be categorized as chemotherapy, immunotherapy, device‐assisted therapy and combined therapy. Combining new with established intravesical treatments seems to hold the most promise. Maintenance thermo‐chemotherapy gives a reported 2‐year disease‐free survival rate of 50% and in small early‐phase studies of intravesical gemcitabine administered in combination with mitomycin‐C, tolerance and efficacy data would suggest the need for larger trials, given the early encouraging results. Electromotive mitomycin‐C given sequentially with BCG might not only reduce the recurrence rate but also reduce progression and disease‐specific mortality, although currently there is no trial in a specific population with ‘BCG failure’.
Relationship of baseline HbA1c and efficacy of current glucose‐lowering therapies: a meta‐analysis of randomized clinical trials
Authors: DeFronzo R. A. , Stonehouse A. H. , Han J. , Wintle M. E.
Published: March 2010

Diabet. Med. 27, 309–317 (2010)

Aims  Baseline glycated haemoglobin (HbA1c) concentrations vary between clinical trials of glucose‐lowering agents and this may affect interpretation of clinical efficacy. The objective of this study is to quantify the relationship between baseline HbA1c and reduction of HbA1c in clinical trials.

Methods  PubMed literature searches from 1991 to 2007. Randomized controlled studies with placebo‐controlled or comparator arms [≥ 9 patients in the intent‐to‐treat (ITT) population] ranging in duration from 23 to 52 weeks, in which baseline and change in glycated haemoglobin (HbA1c) were reported. The relationship between baseline HbA1c and change in HbA1c was analysed by a weighted least‐squared regression model accounting for ITT population and variance of HbA1c change. Fourteen per cent of independently abstracted studies met the selection criteria.

Results  Meta‐analysis from 59 clinical trials (8479 patients) produced weighted R2 of 0.35 (P < 0.0001) for the association of baseline HbA1c and absolute change in HbA1c. Subanalysis of eight metformin clinical trials demonstrated a stronger association [weighted R2 of 0.67 (P = 0.0130)]. Exclusion of metformin clinical trials from the overall meta‐analysis (n = 51) yielded a weighted R2 of 0.31 (P < 0.0001). Subanalyses of clinical trials of glucose‐lowering therapies predominantly targeting fasting (n = 37) or postprandial (n = 22) blood glucose produced weighted R2 values of 0.27 (P < 0.001) and 0.42 (P < 0.005), respectively.

Conclusions  These data demonstrate a positive relationship between baseline HbA1c and the magnitude of HbA1c change across 10 categories of glucose‐lowering therapies, irrespective of class or mode of action. These observations should be considered when assessing clinical efficacy of diabetes therapies derived from clinical trials.
Atherosclerotic disease location and disparities in the control and treatment of cardiovascular risk factors in patients with Type 2 diabetes
Authors: Berthold H. K. , Bestehorn K. P. , Krone W. , Gouni‐Berthold I.
Published: March 2010

Diabet. Med. 27, 303–308 (2010)

Aims  To assess whether differences exist in the control and intensity of medication treatment of cardiovascular risk factors in secondary prevention patients with Type 2 diabetes, depending on their atherosclerotic disease territory [coronary artery disease (CAD), cerebrovascular disease (CBVD) or peripheral arterial disease (PAD)].

Methods  Cross‐sectional analysis of 17 571 patients with Type 2 diabetes with prevalent atherosclerotic disease. Endpoints included uncontrolled cardiovascular disease (CVD) risk factors [systolic blood pressure (SBP) ≥ 140 mmHg, low‐density lipoprotein cholesterol ≥ 3.4 mmol/l and glycated haemoglobin ≥ 8.0%] and high intensity of medication treatment (defined as ≥ 2 classes of anti‐hypertensive agents, ≥ 1 lipid‐lowering agent or either insulin or ≥ 2 oral glucose‐lowering agents) in patients with uncontrolled CVD risk factors. Multiple‐adjusted odds ratios were calculated for CAD, CBVD and PAD after adjusting for sex, age, body mass index, current smoking and diabetes duration.

Results  Proportions of patients with uncontrolled risk factors were significantly different among disease territories. Decreased odds of having lipids not controlled were observed in patients with CAD, while decreased odds of having systolic blood pressure not controlled were observed in patients with PAD. PAD was associated with the highest odds of hyperglycaemia not being controlled. High‐intensity treatment was observed in lipid and blood glucose management but not in hypertension management, independent of disease location.

Conclusions  In subjects with Type 2 diabetes and atherosclerotic disease, control of modifiable CVD risk factors but not intensity of medication treatment is modified by atherosclerotic disease territory. Intensity of medication treatment is different between risk factors.
‘FAMILY’ OWNERSHIP, TUNNELLING AND EARNINGS MANAGEMENT: A REVIEW OF THE LITERATURE
Authors: Bhaumik Sumon Kumar , Gregoriou Andros
Published: March 2010

Abstract In this review paper, we bring together a number of aspects of family firms that are ubiquitous in a number of institutional contexts, often as part of larger business groups. We pay particular attention to the mechanisms by which families retain control over firms, and the incentives of the families in control to expropriate other stakeholders by way of tunnelling. We examine the role of earnings management in facilitating tunnelling, and evidence about the incidence of earnings management in family firms. Our review suggests that while the literature on these aspects of family control is rich, the contexts in which the empirical exercises are undertaken are relatively few, and hence there is considerable opportunity to expand it to other contexts, in particular in the form of cross‐country comparisons of the relative impact of agency conflicts and institutions on these issues.
PRODUCT QUALITY AND MARKET SIZE*
Authors: BERRY STEVEN , WALDFOGEL JOEL
Published: March 2010

Do larger markets offer better products? The question has implications for theories of cities and theories of market organization. We document that in the restaurant industry, where quality is produced largely with variable costs, the range of qualities on offer increases in market size. In daily newspapers, where quality is produced with fixed costs, the average quality of products increases with market size, but the market does not offer much additional variety as it grows large. These results are consistent with IO theories of endogenous product quality and with theories that emphasize the consumption advantages of cities.
COUNTERVAILING POWER IN WHOLESALE PHARMACEUTICALS*
Authors: ELLISON SARA FISHER , SNYDER CHRISTOPHER M.
Published: March 2010

Using data on wholesale prices for antibiotics sold to U.S. drugstores, we test the growing theoretical literature on ‘countervailing power’ (a term for the ability of large buyers to extract discounts from suppliers). Large drugstores receive a modest discount for antibiotics produced by competing suppliers but no discount for antibiotics produced by monopolists. These findings support theories suggesting that supplier competition is a prerequisite for countervailing power. As further evidence for the importance of supplier competition, we find that hospitals receive substantial discounts relative to drugstores, attributed to hospitals' greater ability to induce supplier competition through restrictive formularies.
INFORMATION REVELATION AND BUYER PROFITS IN REPEATED PROCUREMENT COMPETITION*
Authors: THOMAS CHARLES J.
Published: March 2010

I investigate how procurement costs are affected by the information that buyers reveal about sellers' behavior, in a setting with two sequentially offered contracts for which a seller's privately known costs are identical. Expected prices are lowest when sellers learn nothing until all contracts are allocated, are higher when they learn all sellers' price offers as contracts are allocated, and typically are even higher when they learn only the winner's identity, or the winner's identity and price offer. The results suggest that buyers engaged in repeated procurement may pay less by revealing minimal or extensive information, rather than an intermediate amount.
The influence of geographic life environments on cardiometabolic risk factors: a systematic review, a methodological assessment and a research agenda
Authors: Leal C. , Chaix B.
Published: March 2010

Recent environmental changes play a role in the dramatic increase in the prevalence of cardiometabolic risk factors (CMRFs) such as obesity, hypertension, type 2 diabetes, dyslipidemias and the metabolic syndrome in industrialized countries. Therefore, identifying environmental characteristics that are associated with risk factors is critical to develop more effective public health interventions. We conducted a systematic review of the literature investigating relationships between characteristics of geographic life environments and CMRFs (131 articles). Most studies were published after 2006, relied on cross‐sectional designs, and examined whether sociodemographic and physical environmental characteristics, and more recently service environment characteristics, were associated with obesity or, to a lesser extent, hypertension. Only 14 longitudinal studies were retrieved; diabetes, dyslipidemias and the metabolic syndrome were rarely analysed; and aspects of social interactions in the neighbourhood were critically underinvestigated. Environmental characteristics that were consistently associated with either obesity or hypertension include low area socioeconomic position; low urbanization degree; low street intersection, service availability and residential density; high noise pollution; low accessibility to supermarkets and high density of convenience stores; and low social cohesion. Intermediate mechanisms between environmental characteristics and CMRFs have received little attention. We propose a research agenda based on the assessment of underinvestigated areas of research and methodological limitations of current literature.
Potential Payoff from R&D in the Coconut Industry of North Sulawesi, Indonesia
Authors: Henderson Benjamin , Henry Lynn , MacAulay Gordon , Tatuh Jen
Published: March 2010

The coconut industry of North Sulawesi, one of the primary coconut‐producing provinces of Indonesia, is dominated by a small number of products that are primarily exported overseas. As they only comprise a small share of the global coconut product export market, demand for coconut products from North Sulawesi is generally very elastic. Conversely, the supply of coconuts is highly inelastic, especially in the short to medium term. Hence, small shifts in supply and demand lead to large fluctuations in farmer incomes. In this context, an equilibrium displacement model is used to examine the intra‐industry consequences of R&D investments in farm productivity and product development. These investments are assessed in terms of the producer surplus benefits that they generate.
Environmental Performance Assessment of China's Manufacturing
Authors: Zhang Tao
Published: March 2010

This paper applies the data envelopment analysis approach to contribute to the debate on the environmental performance of China's manufacturing sector. Regional and periodic differences in environmental efficiency, environmental quantity and environmental change indexes in China's manufacturing sector are examined for the period between 1998 and 2002. Within the framework of data envelopment analysis and distance functions, environmental quantity and environmental change indexes are measured as variants of the Malmquist quantity index. The overall environmental efficiency of China's manufacturing sector is very low, indicating substantial potential to reduce pollution emissions in China's manufacturing industries. The results and implications of this study can provide helpful information to improve the environmental performance of China's manufacturing sector.
Think Tanks in the United Kingdom and Germany: Actors in the Modernisation of Social Democracy
Authors: Pautz Hartwig
Published: March 2010

This article describes and analyses the role that think tanks in the United Kingdom and Germany played in the modernisation of the British Labour party and the Social Democratic party of Germany between 1992 and 2008. In these years, both parties were de-traditionalised. Especially, their central objective, that of achieving a socially just society, was redefined under the banner of the ‘Third Way’. Policy experts from outside the political parties played an important role in this process. The article discusses what a think tank is and whether in times of ‘paradigmatic’ crisis actors external to a political party can exert influence on the parties' policy objectives and thus supersede internal policy-making institutions. It also analyses, in comparative perspective, the conditions in which think tanks in both countries can be most effective.
Unravelling the process from Closed to Open Innovation: evidence from mature, asset‐intensive industries
Authors: Chiaroni Davide , Chiesa Vittorio , Frattini Federico
Published: March 2010

Open Innovation has been one of the most‐debated topics in management research in the last decade. Although our understanding of this management paradigm has significantly improved over the last few years, a number of important questions are still unanswered. In particular, an issue that deserves further attention is the anatomy of the organizational change process through which a firm evolves from being a Closed to an Open Innovator. The paper represents a first step in overcoming this limitation. In particular, adopting a longitudinal, firm‐level perspective, it addresses the following question: which changes in a firm's organizational structures and management systems does the shift from Closed to Open Innovation entail? In answering this question, the paper uses established concepts in organizational change research to look into a rich empirical basis that documents the adoption of Open Innovation by four Italian firms operating in mature, asset‐intensive industries. The results show that the journey from Closed to Open Innovation involves four main dimensions of the firm's organization, i.e. inter‐organizational networks, organizational structures, evaluation processes and knowledge management systems, along which change could be managed and stimulated.
How Reliable are Income Data Collected with a Single Question?
Authors: Micklewright John , Schnepf Sylke V.
Published: March 2010

Income is an important correlate for numerous phenomena in the social sciences. But many surveys collect data with just a single question covering all forms of income. This raises questions over the reliability of the data that are collected. Issues of reliability are heightened when individuals are asked about the household total rather than own income alone. We argue that the large literature on measuring incomes has not devoted enough attention to ‘single-question’ surveys. We investigate the reliability of single-question data by using the UK Office for National Statistics’s Omnibus survey and the British Social Attitudes survey as examples. We compare the distributions of income in these surveys—individual income in the Omnibus and household income in the British Social Attitudes survey—with those in two larger UK surveys that measure income in much greater detail. Distributions compare less well for household income than for individual income. Disaggregation by gender proves fruitful in much of the analysis. We also establish levels of item non-response to the income question in single-question surveys from a wide range of countries.
IN DEFENCE OF NATURAL DAYLIGHT
Authors: ALLEN KEITH
Published: March 2010

Objects appear different as the illumination under which they are perceived varies. This fact is sometimes thought to pose a problem for the view that colours are mind‐independent properties: if a coloured object appears different under different illuminations, then under which illumination does the object appear the colour it really is? I argue that given the nature of natural daylight, and certain plausible assumptions about the nature of the colours it illuminates, there is a non‐arbitrary reason to suppose that it is under natural daylight that we are able to perceive the real colours of objects.
SELF‐DEFENSE, INNOCENT AGGRESSORS, AND THE DUTY OF MARTYRDOM
Authors: KAUFMAN WHITLEY
Published: March 2010

On the traditional doctrine of self‐defense, defensive force is permissible not only against Culpable Aggressors but against Innocent Aggressors as well (for example, psychotic aggressors). Some moral philosophers have recently challenged this view, arguing that one may not harm innocent attackers because morality requires culpability as an essential condition of being liable to defensive force. This essay examines and rejects this challenge as both a violation of common sense and as insufficiently grounded in convincing reasons from moral theory.
PERFECTION AND DESIRE: SPINOZA ON THE GOOD
Authors: KISNER MATTHEW J.
Published: March 2010

While Spinoza claims that our good is both what increases our essential power and what helps us to satisfy our desires, he admits that people desire things that do not increase their power. This paper addresses this problem by arguing that Spinoza conceives of desires as expressions of our conatus, so that satisfying our desires necessarily increases our power and vice versa. This reading holds, in opposition to recent work, that Spinoza upholds a desire‐satisfaction theory of the good, though an unusual one, since our good is only determined by desires arising from our conatus, in other words, active desires.
INSPECTING THE FOUNDATIONS OF LIBERALISM
Authors: De Jasay Anthony
Published: March 2010

Liberal justice is rooted in a system of conventions. They arise spontaneously as behavioural equilibria that bring mutual advantage to those adopting them. They protect life, limb, property and the pursuit of peaceful purposes, and require the fulfilment of reciprocal promises. Collective choice, where some impose choices on others who submit, violates liberal justice and reduces the set of freedoms. Liberalism and democracy are incompatible as organising principles and ‘liberal democracy’ is a contradiction in terms.