bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Apolipoprotein E ε2 With White Matter Disease but Not With Microbleeds
Authors: Lemmens Robin , Görner Astrid , Schrooten Maarten , Thijs Vincent
Published: February 2007

Background and Purpose—

Apolipoprotein E (apoE) alleles (ε2 and ε4) are associated with cerebral amyloid angiopathy, in which white matter disease and microbleeds are prominent features. The role of apoE in patients with microbleeds or white matter disease but no evidence of cerebral amyloid angiopathy has not been elucidated. We studied apoE alleles in relation to white matter disease and microbleeds in patients with transient ischemic attack or ischemic stroke.

Methods—

We obtained brain MRI scans and apoE genotypes in 334 transient ischemic attack or ischemic stroke patients. Microbleeds were scored on a gradient echo MRI and white matter disease was examined on fluid attenuated inversion recovery MRI using a semiquantitative rating scale.

Results—

Patients with moderate to severe white matter disease more frequently carried apoE ε2 alleles (25.2% versus 11.3%,
P
=0.001), but not apoE ε4 (26.6% in apoE ε4 carriers versus 25.9%;
P
=0.98). Adjustment for traditional risk factors did not modify this relationship (odds ratio, 2.9; 95% confidence interval, 1.5 to 5.3). There was no association between the presence of microbleeds and the apoE ε4 or apoE ε2 alleles.

Conclusions—

ApoE alleles do not exert a major influence on the development of microbleeds, but apoE ε2 may be associated with development of moderate to severe white matter disease in transient ischemic attack and stroke patients.
Characterization of Phosphate Transport in Rat Vascular Smooth Muscle Cells
Authors: Villa-Bellosta Ricardo , Bogaert Yolanda E. , Levi Moshe , Sorribas Víctor
Published: February 2007

Objective—

Hyperphosphatemia and inorganic phosphate (Pi) transport by vascular smooth muscle cells (VSMCs) have been implicated in the pathogenesis of vascular calcification. The aim of this work has been to characterize Pi transport in VSMCs.

Methods and Results—

Primary cultures of VSMCs express both high affinity Na-dependent and Na-independent components of Pi transport. Under physiological conditions both transport systems are saturated, show similar activity, and are inhibited by increasing pH. The Na-dependent transport is also weakly inhibited by phosphonoformic acid (PFA) (3.9 mmol/L IC
50
at 0.05 mmol/L Pi). Real-time polymerase chain reaction shows that Pit1 and Pit2 are expressed to the same degree, and no other Pi transporters are significantly expressed. When expressed in Xenopus oocytes they are strictly Na-dependent, with high affinities for Pi, and are inhibited by increasing pH, but only weakly inhibited by PFA. We have used RNA interference to demonstrate that Pit1 and Pit2 are the transporters responsible for Na-dependent Pi transport in VSMCs.

Conclusions—

Taken together these novel findings suggest new roles of Pi transport in the pathogenesis of VC and have implications as potential future clinical targets.
Activity patterns, behavioural repertoires, and agonistic interactions of crayfish: A non-manipulative field study
Authors: Davis Karen , Huber Robert
Published: February 2007

Agonistic behaviour of crayfish has been studied extensively in laboratory settings where pairs or groups of individuals are allowed to interact within an experimental arena. Crayfish agonistic behaviour within its natural context, however, has received little attention to date. The present, non-manipulative field study explored activity patterns, behavioural repertoires, and agonistic encounters of rusty crayfish (Orconectes rusticus) during the summer months using continuous, 24-hour, underwater video recording at a series of representative field sites. Following the filming, crayfish within the vicinity of the camera site were captured and measured. Individual densities were high, reaching a maximum of 68 individuals/m2 at some sites. Large crayfish predominantly inhabited deeper sections of the river and were mostly active at night, whereas small crayfish generally utilized the shallows and were active outside their burrows during day and dusk. Time outside their shelter was mainly used for feeding. Individuals frequently returned to the same shelter they had emerged from. Agonistic encounters were common events and generally occurred in the context of shelter acquisition or defense. Dyadic fighting progressed with escalating sequences of stereotyped aggressive acts. Furthermore, high intensities with unrestrained use of claws were seen in encounters between size-matched opponents. The results of this study allow us to root laboratory findings of crayfish aggression within a comprehensive, ethological framework and to consider ultimate consequences for individual fighting decisions and strategies.
Carotenoid-based plumage coloration and aggression during molt in male house finches
Authors: Medina-Jerez William , Adams Heather , McGraw Kevin
Published: February 2007

Birds often use colorful traits to mediate resource competitions, and typically individuals with bright or large patches of color are more competitive than or dominant to those with drab or small color patches. Male House Finches (Carpodacus mexicanus) are an exception, however, as drab males tend to be more aggressive than bright males during the breeding season and in winter. One hypothesis for this 'negatively correlated handicap' is that drab male house finches, being comparatively sexually unattractive and in poor health and condition, have more to gain by elevating aggression and increasing access to food and pursuit of (especially extra-pair) mates. It would seem important then to test this hypothesis during the period of molt, when birds are actively acquiring the foods and carotenoid pigments that make them colorful and a time in which there is a clear link between plumage color and nutrition/health in this species. We conducted two captive dominance experiments with male House Finches from the southwestern United States (their native range) to examine the relationship between carotenoid-based plumage coloration and aggression during molt. In the first experiment, where birds exhibited their natural, currently growing plumage color, we found that drab males were significantly more aggressive than bright males. However, when plumage colors were manipulated with art markers in a second experiment, color display was no longer significantly predictive of agonistic outcomes. These results suggest that: (1) drab male dominance is not an artifact in eastern US populations and instead is a conserved property of native and non-native House Finches, (2) like in our previous studies in winter, plumage color is correlated with dominance but does not serve as a visual signal of social status in this species, and (3) drab males should have a competitive advantage over access to important carotenoid-rich foods during molt, but apparently do not become as colorful because they do not adequately locate carotenoid-rich foods or do not use them efficiently for energetic or health reasons, which are perhaps exacerbated by elevated testosterone levels.
Spatial association and social behaviour in zoo-living female ring-tailed coatis (Nasua nasua)
Authors: Aureli Filippo , Romero Teresa
Published: February 2007

Most carnivore species are solitary and tend not to associate either with members of the same sex or with the opposite sex. In contrast, coati adult females and juveniles live in stable groups, called 'bands'. Coatis display complex cooperative behaviours, and their bands resemble primate female-bonded societies in various features. In this study we examined spatial association patterns among zoo-living ring-tailed coatis and related it to the patterns of affiliative and aggressive interactions. We found that coati females did not associate or interact with one another randomly. A cluster analysis on spatial association data revealed two main subunits, the size and composition of which were the same in two observation periods. Furthermore, the distribution of affiliative and aggressive interactions of the coatis reflected patterns of spatial association. Affiliative behaviour was more frequent between members of the same subunit than between members of different subunits, whereas aggressive interactions were more frequent between subunits than within subunits. We discuss the implications of these findings for coati social organisation suggesting that the two subunits may reflect the potential for subgroup formation and fission-fusion dynamics in wild populations.
Lack of Pharmacokinetic Interaction Between Anidulafungin and Tacrolimus
Authors: Dowell James A. , Stogniew Martin , Krause David , Henkel Timothy , Damle Bharat
Published: February 2007

The safety and pharmacokinetics of anidulafungin coadministered with tacrolimus were investigated using a single‐sequence, open‐label design. Healthy volunteers received 5 mg tacrolimus orally on days 1 and 13 of the study. Anidulafungin (200 mg) was administered intravenously on day 4, followed by 100‐mg doses on days 5 through 13. Key pharmacokinetic parameters, including Cmax, AUC, t½, CL, and Vss, were derived from concentration‐time data. The 90% confidence intervals (CIs) of the ratios of mean pharmacokinetic parameters of anidulafungin plus tacrolimus to each drug alone were well within the 80% to 125% bioequivalence range, indicating no pharmacokinetic interaction. This ratio was 101.6 (90% CI: 92.77–111.22) for tacrolimus AUC0‐∞ and 107.2 (90% CI: 105.1–109.4) for anidulafungin AUCss. The 2 drugs were well tolerated, and no drug‐related serious adverse events were reported. Because of its lack of pharmacokinetic interaction with key immunosuppressive agents, anidulafungin is an important option for the prevention and treatment of invasive fungal infections in transplant recipients.
Pomegranate Juice Does Not Impair Clearance of Oral or Intravenous Midazolam, a Probe for Cytochrome P450‐3A Activity: Comparison With Grapefruit Juice
Authors: Farkas Dora , Oleson Lauren E. , Zhao Yanli , Harmatz Jerold S. , Zinny Miguel A. , Court Michael H. , Greenblatt David J.
Published: February 2007

The effect of pomegranate juice (PJ) or grapefruit juice (GFJ) on CYP3A activity was studied in vitro and in healthy human volunteers. In human liver microsomes, the mean 50% inhibitory concentrations (IC50) for PJ and GFJ versus CYP3A (triazolam α‐hydroxylation) were 0.61% and 0.55%, (v/v) respectively, without preincubation of inhibitor with microsomes. After preincubation, the IC50for PJ increased to 0.97% (P< .05), whereas the IC50for GFJ decreased to 0.41% (P< .05), suggesting mechanism‐based inhibition by GFJ but not PJ. Pretreatment of volunteer subjects (n = 13) with PJ (8 oz) did not alter the elimination half‐life, volume of distribution, or clearance of intravenous midazolam (2 mg). Administration of PJ also did not affect Cmax, total area under the curve (AUC), or clearance of oral midazolam (6 mg). However, GFJ (8 oz) increased midazolam Cmaxand AUC by a factor of 1.3 and 1.5, respectively, and reduced oral clearance to 72% of control values. Thus, PJ does not alter clearance of intravenous or oral midazolam, whereas GFJ impairs clearance and elevates plasma levels of oral midazolam.
Battered Black Women's Use of Religious Services and Spirituality for Assistance in Leaving Abusive Relationships
Authors: Potter Hillary
Published: February 2007

Though there is substantial rationale to consider any association between spirituality and religion and intimate partner violence, research in this area is particularly lacking. African Americans are known to utilize religion and spirituality at significant rates to deal with adversity. Accordingly, any investigation of Black women's methods of contending with abusive relationships would be deficient if it did not include an examination of the women's use of ecclesiastical resources. Using 40 semistructured in-depth interviews with battered Black women, this article explores the participants' successes and discontent with religion and spirituality to escape abuse.
Control systems for membrane fusion in the ancestral eukaryote; evolution of tethering complexes and SM proteins
Authors: Koumandou V Lila , Dacks Joel B , Coulson Richard MR , Field Mark C
Published: February 2007

Background

In membrane trafficking, the mechanisms ensuring vesicle fusion specificity remain to be fully elucidated. Early models proposed that specificity was encoded entirely by SNARE proteins; more recent models include contributions from Rab proteins, Syntaxin-binding (SM) proteins and tethering factors. Most information on membrane trafficking derives from an evolutionarily narrow sampling of model organisms. However, considering factors from a wider diversity of eukaryotes can provide both functional information on core systems and insight into the evolutionary history of the trafficking machinery. For example, the major Qa/syntaxin SNARE families are present in most eukaryotic genomes and likely each evolved via gene duplication from a single ancestral syntaxin before the existing eukaryotic groups diversified. This pattern is also likely for Rabs and various other components of the membrane trafficking machinery.

Results

We performed comparative genomic and phylogenetic analyses, when relevant, on the SM proteins and components of the tethering complexes, both thought to contribute to vesicle fusion specificity. Despite evidence suggestive of secondary losses amongst many lineages, the tethering complexes are well represented across the eukaryotes, suggesting an origin predating the radiation of eukaryotic lineages. Further, whilst we detect distant sequence relations between GARP, COG, exocyst and DSL1 components, these similarities most likely reflect convergent evolution of similar secondary structural elements. No similarity is found between the TRAPP and HOPS complexes and the other tethering factors. Overall, our data favour independent origins for the various tethering complexes. The taxa examined possess at least one homologue of each of the four SM protein families; since the four monophyletic families each encompass a wide diversity of eukaryotes, the SM protein families very likely evolved before the last common eukaryotic ancestor (LCEA).

Conclusion

These data further support a highly complex LCEA and indicate that the basic architecture of the trafficking system is remarkably conserved and ancient, with the SM proteins and tethering factors having originated very early in eukaryotic evolution. However, the independent origin of the tethering complexes suggests a novel pattern for increasing complexity in the membrane trafficking system, in addition to the pattern of paralogous machinery elaboration seen thus far.
APC/C – the master controller of origin licensing?
Authors: Sivaprasad Umasundari , Machida Yuichi J , Dutta Anindya
Published: February 2007

DNA replication must be tightly controlled to prevent initiation of a second round of replication until mitosis is complete. So far, components of the pre-replicative complex (Cdt1, Cdc6 and geminin) were considered key players in this regulation. In a new study, Machida and Dutta have shown that depletion of Emi1 caused cells to replicate their DNA more than once per cell cycle [1]. This effect was dependent on the ability of Emi1 to inhibit the APC/C. In addition to its role in regulating entry into mitosis, oscillation of APC/C activity regulates pre-RC formation: high APC/C activity in late M/G1 allows pre-RC formation and low APC/C activity in S/G2 prevents pre-RC formation for a second time thereby preventing rereplication. Each redundant pathway to prevent rereplication is dependent on regulating one of the pre-RC components, and all of the pathways are co-regulated by Emi1 through the APC/C. In this commentary we discuss how this new role of Emi1 adds to our understanding of the regulation of replication initiation. We also review the literature to analyze whether APC/C has a role in regulating endoreduplication (a normal state of polyploidy in some differentiated cells). Similarly a role of premature APC/C activation in genomic instability of tumors is discussed.
Risk factors for post-traumatic stress disorder symptoms following critical illness requiring mechanical ventilation: a prospective cohort study
Authors: Girard Timothy D , Shintani Ayumi K , Jackson James C , Gordon Sharon M , Pun Brenda T , Henderson Melinda S , Dittus Robert S , Bernard Gordon R , Ely EWesley
Published: February 2007

Introduction

Post-traumatic stress disorder (PTSD) has been identified in a significant portion of intensive care unit (ICU) survivors. We sought to identify factors associated with PTSD symptoms in patients following critical illness requiring mechanical ventilation.

Methods

Forty-three patients who were mechanically ventilated in the medical and coronary ICUs of a university-based medical center were prospectively followed during their ICU admission for delirium with the Confusion Assessment Method for the ICU. Additionally, demographic data were obtained and severity of illness was measured with the APACHE II (Acute Physiology and Chronic Health Evaluation II) score. Six months after discharge, patients were screened for PTSD symptoms by means of the Post-Traumatic Stress Syndrome 10-Questions Inventory (PTSS-10). Multiple linear regression was used to assess the association of potential risk factors with PTSS-10 scores.

Results

At follow-up, six (14%) patients had high levels of PTSD symptoms. On multivariable analysis, women had higher PTSS-10 scores than men by a margin of 7.36 points (95% confidence interval [CI] 1.62 to 13.11; p = 0.02). Also, high levels of PTSD symptoms were less likely to occur in older patients, with symptoms declining after age 50 (p = 0.04). Finally, although causation cannot be assumed, the total dose of lorazepam received during the ICU stay was associated with PTSD symptoms; for every 10-mg increase in cumulative lorazepam dose, PTSS-10 score increased by 0.39 (95% CI 0.17 to 0.61; p = 0.04). No significant relationship was noted between severity of illness and PTSD symptoms or duration of delirium and PTSD symptoms.

Conclusion

High levels of PTSD symptoms occurred in 14% of patients six months following critical illness necessitating mechanical ventilation, and these symptoms were most likely to occur in female patients and those receiving high doses of lorazepam. High levels of PTSD symptoms were less likely to occur in older patients.
Pancreatic Glucokinase Is Activated by Insulin-Like Growth Factor-I
Authors: Yoshida Kazuya , Murao Koji , Imachi Hitomi , Cao Wen M. , Yu Xiao , Li Junhua , Ahmed Rania A. M. , Kitanaka Noriko , Wong Norman C. W. , Unterman Terry G. , Magnuson Mark A. , Ishida Toshihiko
Published: February 2007

Glucokinase (GK) plays a key role in the regulation of glucose use and glucose-stimulated insulin secretion in pancreatic islet cells. Gene targeting of the IGF-I receptor down-regulated pancreatic islet GK activity. That finding prompted us to examine the potential mechanism that may control GK gene activity using an islet cell line, INS-1, known to express IGF-I receptor. Exposure of these cells to IGF-I induced GK protein expression and activity of the enzyme in a dose-dependent manner. In addition, IGF-I induced activity of a reporter construct containing the GK promoter in parallel with the effect on endogenous GK mRNA levels. The stimulatory effect of IGF-I on GK promoter activity was abrogated by wortmannin and LY294002, specific inhibitors of phosphatidylinositol 3-kinase. Exposure of cells to IGF-I elicited a rapid phosphorylation of Akt and FoxO1, a known target of Akt signaling. Constitutively active Akt stimulates the activity of the GK promoter, and a dominant-negative mutant of Akt or mutagenesis of a FoxO1 response element in the GK promoter abolished the ability of IGF-I to stimulate the promoter activity. Furthermore, cell knockdown of FoxO1 with small interfering RNA disrupted the effect of IGF-I on GK expression. These results demonstrate that the phosphatidylinositol 3-kinase/Akt/FoxO1 pathway contributes to the regulation of GK gene expression in response to IGF-I stimulation.
Expression of Anti-Mullerian Hormone Protein during Early Follicular Development in the Primate Ovary in Vivo Is Influenced by Suppression of Gonadotropin Secretion and Inhibition of Vascular Endothelial Growth Factor
Authors: Thomas Fiona H. , Telfer Evelyn E. , Fraser Hamish M.
Published: February 2007

Anti-Mullerian hormone (AMH) plays a role during early follicular development and selection. The aim of this study was to determine the pattern of AMH protein expression in the marmoset ovary and to investigate the effects of inhibition of gonadotropins or vascular endothelial growth factor (VEGF) activity on AMH expression in vivo. GnRH antagonist or VEGF Trap, a soluble decoy receptor, was administered on d 0 or 5 of the follicular phase of the cycle, and ovaries were collected at the end of the follicular phase (d 10). AMH protein was expressed in the marmoset ovary in granulosa cells from the primary stage, with the most abundant staining at the preantral and early antral stages. Inhibition of gonadotropin secretion or VEGF activity between d 0–10 of the cycle decreased AMH expression in early preantral follicles (P < 0.01), and AMH expression was decreased in late preantral follicles in the presence of the VEGF Trap (P < 0.01), compared with controls. There was significantly less AMH expression in early antral follicles with both treatments (P < 0.01), and a decrease in the ratio of oocyte-associated/basement-membrane-associated granulosa cell expression of AMH (P < 0.05). When treatments were administered from d 5–10 of the cycle, both VEGF Trap and GnRH antagonist decreased AMH expression in preantral follicles (P < 0.01) but had no significant effect on early antral follicles. In conclusion, VEGF and gonadotropins are involved in the regulation of expression of AMH in the marmoset. This AMH expression may be a marker of abnormal folliculogenesis in the absence of gonadotropin stimulation or functional angiogenesis.
Identification and Characterization of Two Nuclear Factor-κB Sites in the Regulatory Region of the Dopamine D2 Receptor
Authors: Bontempi Sandra , Fiorentini Chiara , Busi Chiara , Guerra Nicoletta , Spano PierFranco , Missale Cristina
Published: February 2007

Regulation of D2 receptor (D2R) expression is crucial in the function of dopaminergic systems. Because alterations of D2R expression may contribute to the development of different disorders, it is important to elucidate the mechanisms regulating D2R gene transcription. We report the characterization of two putative nuclear factor-κB (NF-κB) motifs, referred to as D2-κB sites, in the human D2R promoter, and demonstrate that they bind NF-κB subunits and stimulate D2R promoter activity. D2-κB sites show different degrees of conservation and specificity, when compared with canonical kB sites. The D2-κB1 site (from −407 to −398) is highly conserved and binds p50/p65 and p50/c-Rel complexes, whereas D2-κB2 (from −513 to −504) is more degenerated and only binds p50/p65 heterodimers. Activation of D2-κB sites in COS-7 cells expressing a luciferase reporter vector containing the D2R promoter resulted in increased transcriptional activity. Site-directed mutagenesis of each D2-κB site differentially modified D2R promoter activity. In particular, mutation of the D2-κB1 motif did not affect D2R promoter response to p50/c-Rel complexes, whereas inactivation of the D2-κB2 site decreased it. Mutations of either D2-κB1 or D2-κB2 sites attenuated the D2R promoter transcriptional efficiency induced by p50/p65 complexes. Thus, D2R transcription mediated by p50/c-Rel is supported mainly by the D2-κB2 site, whereas both sites are necessary to support the full transcriptional activity mediated by p50/p65 complexes. A correlation was found between NF-κB activity and D2R expression in the pituitary and pituitary-derived cells but not in the striatum, suggesting that NF-κB regulation of D2R expression could be a pituitary-specific mechanism.
Differential Hormonal Regulation and Function of Progesterone Receptor Isoforms in Normal Adult Mouse Mammary Gland
Authors: Aupperlee Mark D. , Haslam Sandra Z.
Published: February 2007

In normal mouse mammary gland, the mitogenic action of progesterone (P) is mediated by two P receptor (PR) isoforms, PRA and PRB. PRA is predominantly expressed in the adult virgin, and PRB is predominantly expressed during pregnancy. To investigate hormonal regulation of PR isoform expression and isoform-specific functions in vivo, adult ovariectomized BALB/c mice were treated for 3, 5, or 10 d with estrogen (E), P, or estrogen plus progesterone (E+P). Using an immunohistochemical approach with isoform-specific antibodies, we investigated hormonal regulation of PRA and PRB and their functional roles in proliferation and morphogenesis. Significant E-induced proliferation was only observed after 5 d at the distal tips of ducts; there was no sidebranching or alveologenesis. P induced proliferation that resulted in sidebranching and alveologenesis, but E+P treatment produced more proliferation sooner and more extensive sidebranching and alveologenesis. PRA levels were increased by E and decreased by P. Increased PRB levels were induced by treatment with P or E+P and coincided with the formation of alveoli. PRA was the predominant PR isoform expressed during sidebranching, and colocalization of PRA with 5-bromo-2′-deoxyuridine revealed that proliferation of PRA-positive and -negative cells was responsible for P-induced sidebranching. PRB was the predominant PR isoform expressed during alveologenesis, and colocalization of PRB with 5-bromo-2′-deoxyuridine showed that both PRB-positive and -negative cells proliferated during alveolar expansion. These results demonstrate different hormonal regulation of PRA and PRB levels in vivo and suggest that P can induce proliferation through either PRA or PRB via direct and paracrine mechanisms.
Markets: Cartel Behavior and Amateurism in College Sports
Authors: Kahn Lawrence M
Published: February 2007

This paper studies intercollegiate athletics in the context of the theory of cartels. Some point to the explicit attempts by the National Collegiate Athletic Association (NCAA) to restrict output and payments for factors of production as evidence of cartel behavior. Others argue that such limits enhance product quality by preserving amateurism. I find that the NCAA's compensation limits on athletes lead to high levels of rents from the entertainment revenues produced by the athletes, a finding consistent with the cartel interpretation. The athletes producing these rents are disproportionately African-American, while the beneficiaries are primarily white. The rents are typically spent on facilities, nonrevenue sports, and, possibly, head coaches' salaries. Big-time football and men's basketball programs earn accounting profits, although the athletic departments in which they reside make accounting losses on average. However, there is some evidence, albeit not unanimous, that sports generate alumni contributions, state appropriations, and additional student applications. But, arms race considerations suggest that there may be some societal gains to the aggregate limitation of spending on college athletics.
Audit of syphilis treatment, follow-up and contact-tracing rates
Authors: Fernando I , Thompson C
Published: February 2007

An audit of diagnoses of syphilis infection managed at the Edinburgh genitourinary (GU) medicine clinic for the period 1 October 2001–31 October 2004. In all, 101 patients were identified as untreated carriers or contacts requiring treatment, partner notification and follow-up. Treatment rate was 100% in the audit population. Among this patient group, 90% were offered testing for other sexually transmitted infections (STIs) with a positivity rate of 24%. The HIV testing rate was 85%, resulting in five new diagnoses.
A comparison of self-taken vulvovaginal and cervical samples for the diagnosis of Chlamydia trachomatis infection by polymerase chain reaction
Authors: Keane F E A , Bendall Richard , Saulsbury N , Haddon Lisa
Published: February 2007

Implementation of the National Chlamydia Screening Programme in Cornwall commenced in April 2003. Initially, women in community venues were screened using urine samples. However, many of these urine samples were inhibitory to polymerase chain reaction (PCR), resulting in a high recall rate for women in the programme. The decision to switch to self-taken vulvovaginal samples led us to carry out an in-house validation of this sample compared with endocervical samples. Data from 333 women were analysed. Of the endocervical samples, 15.9% were positive compared with 16.8% vulvovaginal samples. This difference between positivity rates in cervical and self-taken vulvovaginal samples is not significant. Equivocal results occurred with 4.7% of the vulvovaginal samples but were not seen with the endocervical samples. Self-taken vulvovaginal samples are acceptable to women, as sensitive as endocervical swabs and more suited to PCR testing with the Roche COBAS Amplicor system than urine samples.
Is there a role for leucocyte esterase testing in non-invasive screening using nucleic acid amplification tests of asymptomatic men?
Authors: Horner Patrick J , Taylor-Robinson David
Published: February 2007

With the increasing pressure to achieve the government's 48 hour access target for departments of genitourinary (GU) medicine better utilization of resources must be part of the solution. The leucocyte esterase (LE) test has been shown to perform as well as a urethral smear in asymptomatic men in identifying chlamydia-positive individuals and is likely to perform better in detecting genitalium-positive individuals than chlamydia-positive men. The LE test, which is both inexpensive and non-invasive, offers an interim, evidence-based, solution to the issue of whether asymptomatic men attending departments of GU medicine should be screened for the presence of urethral inflammation.
Dose reduction effective in alleviating symptoms of saquinavir toxicity
Authors: Stephan C , Carlebach A , Rottmann C , Haberl A , Dauer B , von Hentig N , Kurowski M , Staszewski S
Published: February 2007

Gastrointestinal intolerance is a limitation of boosted saquinavir antiretroviral treatment. We present three HIV-infected individuals whose severe toxicity symptoms started directly after initiation of a standard dose saquinavir hard-gel capsule-containing regimen (saquinavir/ritonavir 1000/100 mg). All patients underwent immediate 12 h pharmacokinetic (PK) assessment and showed extraordinarily high saquinavir plasma exposure. All three patients did not recover until the saquinavir exposure was decreased. This pilot case study anticipates a new concept of 'direct PK'-guided individual dose interventions under close viral load monitoring. Two major reasons for symptomatic saquinavir overexposure were defined: impaired liver function in a chronic hepatitis C virus co-infected individual at normal liver performance parameters and a delayed cytochrome p450 enzyme autoinduction. Overexposure seems to be an independent intolerance factor. Although delayed autoinduction is not well established as a reason for adverse events in saquinavir therapy, this observation may be confirmed in the near future by increased use.
Rapid HIV testing, pregnancy, antiretroviral prophylaxis and infant abandonment in St Petersburg
Authors: Hillis Susan D , Rakhmanova Aza , Vinogradova Elena , Voronin Evgeny , Yakovlev Alexei , Khaldeeva Natalia , Akatova Natalia , Samarskaya Mida , Volkova Galina , Kissin Dmity , Jamieson Denise J , Glynn M Kathleen , Robinson Joanna , Miller William C
Published: February 2007

In St Petersburg, Russia, a rapid HIV-testing programme was implemented in April 2004 for high-risk women giving birth. Among 670 women without prenatal care who received rapid HIV testing, 6.4% (43) had positive results. Among HIV-positive mothers, receipt of intrapartum antiretroviral prophylaxis increased significantly compared to pre-programme levels (76 versus 41%). Additionally, infant abandonment increased significantly (50% versus 26%), and was 10 times greater in women with unintended versus intended pregnancies (73% versus 7%).
HIV-infected pregnant women have greater adherence with antiretroviral drugs than non-pregnant women
Authors: Vaz Maria José Rodrigues , Barros Sonia Maria Oliveira , Palacios Ricardo , Senise Jorge Figueiredo , Lunardi Luciana , Amed Abes Mahmed , Castelo Adauto
Published: February 2007

The objective of the study was to evaluate the influence of pregnancy on the level of adherence with antiretroviral (ARV) drugs, in a prospective cohort of 72 pregnant women and 79 non-pregnant women. Adherence was measured by pill counting and self-reporting. Women were deemed adherent if 95% or more of all ARV had been taken as prescribed, in two occasions. According to pill counting, 43.1 and 17.7% of pregnant and non-pregnant women, respectively, met the criteria of adherence ( P = 0.001); in the postpartum, adherence declined to 20.6% ( P = 0.002). In both groups, adherence rates by self-reporting were significantly higher as compared with pill counting ( P = 0.001). In multivariate regression analysis, age >29 years (odds ratio [OR] 3.58, confidence interval [CI] 95% 0.10–0.75, P = 0.011), mean number of pills/day <6 (OR 2.53, CI 95% 1.07–6.01, P = 0.035), and being pregnant (OR 3.33, CI 95% 1.36–8.13, P = 0.008) were independently associated to greater adherence.
Validity of self-reported 'safe sex' among female sex workers in Mombasa, Kenya—PSA analysis
Authors: Gallo M F , Behets F M , Steiner M J , Thomsen S C , Ombidi W , Luchters S , Toroitich-Ruto C , Hobbs M M
Published: February 2007

We assessed the validity of self-reported sex and condom use by comparing self-reports with prostate-specific antigen (PSA) detection in a prospective study of 210 female sex workers in Mombasa, Kenya. Participants were interviewed on recent sexual behaviours at baseline and 12-month follow-up visits. At both visits, a trained nurse instructed participants to self-swab to collect vaginal fluid specimens, which were tested for PSA using enzyme-linked immunosorbent assay (ELISA). Eleven percent of samples ( n = 329) from women reporting no unprotected sex for the prior 48 hours tested positive for PSA. The proportions of women with this type of discordant self-reported and biological data did not differ between the enrolment and 12-month visit (odds ratio [OR] 1.1; 95% confidence interval [CI] 0.99, 1.2). The study found evidence that participants failed to report recent unprotected sex. Furthermore, because PSA begins to clear immediately after exposure, our measures of misreported semen exposure likely are underestimations.
Lymphogranuloma venereum: an emerging cause of proctitis in men who have sex with men
Authors: Richardson Daniel , Goldmeier David
Published: February 2007

Before 2003, lymphogranuloma venereum (LGV) was rare in developed nations. Several large clusters of LGV in men who have sex with men have been reported across Europe and in the United States of America (USA) since 2003. LGV is caused by L1, L2 and L3 serovars of Chlamydia trachomatis and is a sexually transmitted infection. LGV causes genital ulcers, infected inguinal lymph nodes (buboes) and proctitis/proctocolitis. Treatment with a three-week course of doxycycline prevents rectal strictures, bowel obstruction, bowel perforation and possibly death. Clinicians seeing men who have sex with men with inguinal lymphadenopathy and bowel symptoms should be aware of this current epidemic.
Lamivudine-associated macrocytosis in HIV-infected patients
Authors: Khawcharoenporn Thana , Shikuma Cecilia M , Williams Andrew E , Chow Dominic C
Published: February 2007

Macrocytosis has been increasingly observed in HIV-infected population and is an early indicator of bone marrow toxicity. A retrospective study was conducted among these patients in a HIV clinic to assess risk factors of macrocytosis. We found that lamivudine was strongly associated with macrocytosis (OR = 24.6 [2.9–3223.0], P = 0.001). This association may be due to lamivudine's effect on erythrocyte synthesis.
Management of rape/sexual assault cases within genitourinary medicine clinics: results from a study in North Thames
Authors: Obeyesekera S , Jones K , Forster G E , Welch J , Brook M G , Daniels D ,   North Thames Gumhiv Audit Group
Published: February 2007

A regional audit was undertaken to evaluate current practice in the management of survivors of sexual assault (SA) seen in genitourinary (GU) medicine clinics in the North Thames. The majority of the survivors were women. Most were fast-tracked, or seen in dedicated SA clinics. Over 60% of staff had specific training in management of SA. Core services provided included screening and treatment for sexually transmitted infections, emotional support, emergency contraception and hepatitis B vaccination. The sexual health needs of these survivors of SA are being met by most clinics. The development and use of a standardized care proforma across the region may be a means to further improve the care provided.
Should the child live? Doctors, families and conflict
Authors: Glover Jonathan
Published: February 2007

It is a terrible thing to let a child die against the deeply held and clearly expressed view of the child's parents. Yet it could be claimed that there are some conditions so burdensome that it may also be a terrible thing to deny a child the escape of death. The focus of this piece is on three ethical issues relating to withholding and withdrawal of treatment in a neonatal and paediatric context. The first is whether there are other interests that should be considered as well as those of the child. The second is how we should think about the interests of the child. The third is a set of issues raised by cases where the medical team and the family reach different conclusions about what it is best to do. Reference is made to the recent cases of Charlotte Wyatt and Luke Winston-Jones.
The relationship between medical law and ethics
Authors: Miola J
Published: February 2007

This article seeks to identify a 'problem' in the interaction between medical law and ethics, which is that neither fully appreciates how the other works. In particular, it argues that medical law has not only failed to formulate a consistent conception of the role that medical ethics performs, but it does not adequately differentiate between categories of medical ethics discourse. Consequently, the ethical content of a case, if identified at all, will not be dealt with in a consistent manner. The article further argues that medical ethics does not recognize the power that law gives to it, and that the result is a regulatory vacuum. It then uses the findings of the Bristol Royal Infirmary Report to demonstrate, by analogy, how this may lead to problems.
A brief guide to the Human Tissue Act 2004
Authors: Brazier M , Fovargue S
Published: February 2007

The Human Tissue Act 2004 is designed to regulate the storage and use of organs and tissues from the living, and the removal, storage and use of the same material from the deceased. It repeals much criticized legislation, including the Human Tissue Act 1961, and establishes a Human Tissue Authority to ensure compliance with the Act via a licensing and monitoring regime. When the Act comes into force, probably in April 2006, it will be a criminal offence not to comply with certain provisions of the Act, and a new offence of DNA 'theft' will be introduced. Importantly, the Act places consent at the centre of the system, both from the living and from or on behalf of the deceased.
Seeking ethical approval: opening up the lines of communication
Authors: Hallowell Nina , Lawton Julia
Published: February 2007

This paper attempts to open debate about the nature of and need for ethical review of health-related social science research. Drawing upon personal experience and anecdotal reports we describe some of the problems social scientists and ethics committee members may encounter when social science research is reviewed by Multicentre and Local Research Ethics Committees. We argue that the boundary between research methods and ethics is ambiguous and flexible, and that ethics therefore permeates research at all levels from the construction of the research question to the ways in which data are collected and disseminated. We suggest that the dissatisfaction both sides may experience may be mitigated by more communication and a willingness to understand the others' definition of what counts as ethics and how research is organized and executed. We conclude that ethical review has great potential to strengthen research, and that we must work hard to avoid a situation in which ethical review is seen as just a bureaucratic exercise.
User involvement leads to more ethically sound research
Authors: Staley Kristina , Minogue Virginia
Published: February 2007

Involving service users and carers in clinical research can help to improve its quality and relevance. By defining the limits of ethical acceptability, improving research design and management, ensuring information for participants is accessible and ensuring the views of participants are properly respected, user involvement can also improve the ethical conduct of research. But research proposals with good quality user involvement have experienced difficulties in obtaining ethical approval. Not all Research Ethics Committees (RECs) fully understand the active role of service user/carer researchers and the current review system can act as a barrier to involving service users and carers in research. This problem urgently needs to be addressed because it is actually in the interests of RECs to promote and support user involvement. This will require adapting the systems of ethical approval, providing further training for REC members and involving service users and carers in developing and implementing these changes.
Medical studies with 'no material ethical issues' - an unhelpful, confusing and potentially unethical suggestion
Authors: Yentis S M , Dawson A J
Published: February 2007

Both the recent 'Warner' review of the UK research ethics committee (REC) system and the subsequent consultation document produced by the Central Office for Research Ethics Committees (COREC) emphasize the need to distinguish 'research' from what might be termed 'non-research'. This is to be determined through a process of filtering or 'triage', the intention being that RECs will avoid considering proposals with 'no material ethical issues'. In this paper we argue that trying to distinguish 'true' research from other projects is counterproductive, misleading and potentially unethical. Our case is built around three assertions: (1) the distinction between research and non-research is imprecise; (2) both medical research and non-research can generate similar ethical issues; and (3) projects should be judged according to what they involve, not how they are labelled.
Ethics in the face of uncertainty: preparing for pandemic flu
Authors: Sheather Julian
Published: February 2007

The recent appearance of an extremely widespread avian influenza virus (H5N1) that has crossed to humans in highly pathogenic form has lead to speculation that another outbreak of pandemic influenza could be imminent. However, neither the timing of the pandemic, nor the nature and epidemiology of the virus, can be predicted. This uncertainty presents major difficulties in identifying relevant ethical issues in decision-making. If the next pandemic is relatively mild, decisions may be restricted to prioritizing access to essential health services during the peak of the pandemic. If the virus is more pathogenic, social stability may be threatened. It is clear that, irrespective of the nature of the next pandemic, health professionals will have a key role in decisions about allocating scarce health resources during its acute stages. It is essential that they are not forced to make decisions without the support of established guidance or protocols. Any such guidance must be practical (decisions will often have to be made rapidly on the basis of imperfect information), reasoned, based upon sound moral principles, and must enjoy as far as possible the confidence of the wider population. This paper looks in brief at some of the ethical issues that need to be considered when planning a response to pandemic flu.
Consent to the use of aborted fetuses in stem cell research and therapies
Authors: Pfeffer N , Kent J
Published: February 2007

This paper identifies the legal and policy framework relating to the use of aborted fetuses in stem cell research and therapies and contrasts this with the collection of embryos for research. It suggests that more attention should be given to questions about the kind of consent sought by researchers from women and that there should be more transparency about how aborted fetuses are used. It reports on variability in current practices of research ethics committees and researchers and uncertainty about the guidance available to them. It argues that there is a need for wide public discussion about the policy issues relating to fetal tissue use in stem cell research and the need for clarification of the law in this area.
Size Really Matters—New Insights for Start-ups’ Survival
Authors: Raz Ornit , Gloor Peter A.
Published: February 2007

This paper presents new evidence regarding a firm’s probability for survival, based on the network structure of the firm’s managers. We found that start-ups that have larger informal communication networks increased their chance to survive external shock. Original data have been collected from Israeli software start-ups during the dot-com economic growth. About eight years later, we added information about their ability to survive the burst of the dot-com bubble. From a theoretical point of view, this paper highlights the power of the classic social networks approach in explaining organizational performance. From a practical point of view, these findings offer some guidelines for managers of start-ups. Our results show that the size of informal interfirm networks really matters.
Dynamic Assortment with Demand Learning for Seasonal Consumer Goods
Authors: Caro Felipe , Gallien Jérémie
Published: February 2007

Companies such as Zara and World Co. have recently implemented novel product development processes and supply chain architectures enabling them to make more product design and assortment decisions during the selling season, when actual demand information becomes available. How should such retail firms modify their product assortment over time in order to maximize overall profits for a given selling season? Focusing on a stylized version of this problem, we study a finite horizon multiarmed bandit model with several plays per stage and Bayesian learning. Our analysis involves the Lagrangian relaxation of weakly coupled dynamic programs (DPs), results contributing to the emerging theory of DP duality, and various approximations. It yields a closed-form dynamic index policy capturing the key exploration versus exploitation trade-off and associated suboptimality bounds. In numerical experiments its performance proves comparable to that of other closed-form heuristics described in the literature, but this policy is particularly easy to implement and interpret. This last feature enables extensions to more realistic versions of the motivating dynamic assortment problem that include implementation delays, switching costs, and demand substitution effects.