2019 European guideline on the management of lymphogranuloma venereum.

New or important issues in this updated version of the 2013 European guideline on the management of lymphogranuloma venereum (LGV): EPIDEMIOLOGY: Lymphogranuloma venereum continues to be endemic among European men who have sex with men (MSM) since 2003. Lymphogranuloma venereum infections in heterosexuals are extremely rare in Europe, and there is no evidence of transmission of LGV in the European heterosexual population. AETIOLOGY AND TRANSMISSION: Chlamydia trachomatis serovars/genovars L2b and L2 are the causative strains in the majority of cases in Europe. CLINICAL FEATURES: Among MSM, about 25% of the anorectal LGV infections are asymptomatic. Genital infections among MSM are rare; the ratio of genital vs. anorectal LGV infections is 1 in 15. DIAGNOSIS: To diagnose LGV, a sample tested C. trachomatis positive with a commercial nucleic acid amplification test (NAAT) platform should be confirmed with an LGV discriminatory NAAT. TREATMENT: Doxycycline 100 mg twice a day orally for 21 days is the recommended treatment for LGV. This same treatment is recommended also in asymptomatic patients and contacts of LGV patients. If another regimen is used, a test of cure (TOC) must be performed.

Does access to a portable ophthalmoscope improve skill acquisition in direct ophthalmoscopy? A method comparison study in undergraduate medical education.

BACKGROUND: Direct ophthalmoscopy (DO) is an essential skill for medical graduates but there are multiple barriers to learning this. Medical students and junior doctors typically lack confidence in DO. Most students do not own an ophthalmoscope and learn via ward devices that vary in design and usability. The Arclight ophthalmoscope (AO) is an easy to use, low-cost and portable device that could help address device access. This study aimed to assess the impact of personal ownership of an AO on DO skill acquisition and competency amongst medical students in the clinical environment. METHODS: Method comparison study with 42 medical students randomised to either traditional device ophthalmoscope (TDO) control or AO intervention group during an 18-week medical placement. Three objective assessments of DO competency were performed at the beginning and end of the placement: vertical cup to disc ratio (VCDR) measurement, fundus photo multiple-choice questions (F-MCQ) and model slide examination (MSE). DO examinations performed during the placement were recorded via an electronic logbook. RESULTS: Students in both groups recorded a median number of six examinations each during an eighteen-week placement. There was no statistically significant difference between the groups in any of the objective assessment measures (VCDR p = 0.561, MCQ p = 0.872, Model p = 0.772). Both groups demonstrated a minor improvement in VCDR measurement but a negative performance change in F-MCQ and MSE assessments. CONCLUSIONS: Students do not practice ophthalmoscopy often, even with constant access to their own portable device. The lack of significant difference between the groups suggests that device access alone is not the major factor affecting frequency of DO performance and consequent skill acquisition. Improving student engagement with ophthalmoscopy will require a more wide-ranging approach.

The "3 in 1" Study: Pooling Self-Taken Pharyngeal, Urethral, and Rectal Samples into a Single Sample for Analysis for Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in Men Who Have Sex with Men.

Triple-site testing (using pharyngeal, rectal, and urethral/first-void urine samples) for Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests detects greater numbers of infections among men who have sex with men (MSM). However, triple-site testing represents a cost pressure for services. MSM over 18 years of age were eligible if they requested testing for sexually transmitted infections (STIs), reported recent sexual contact with either C. trachomatis or N. gonorrhoeae, or had symptoms of an STI. Each patient underwent standard-of-care (SOC) triple-site testing, and swabs were taken to form a pooled sample (PS) (pharyngeal, rectal, and urine specimens). The PS was created using two methods during different periods at one clinic, but we analyzed the data in combination because the sensitivity of the two methods did not differ significantly for C. trachomatis (P = 0.774) or N. gonorrhoeae (P = 0.163). The sensitivity of PS testing (92%) was slightly lower than that of SOC testing (96%) for detecting C. trachomatis (P = 0.167). For N. gonorrhoeae, the sensitivity of PS testing (90%) was significantly lower than that of SOC testing (99%) (P < 0.001). When pharynx-only infections were excluded, the sensitivity of PS testing to detect N. gonorrhoeae infections increased to 94%. Our findings show that pooling of self-taken samples could be an effective and cost-saving method, with high negative predictive values. (Interim results of this study were presented at the BASHH 2013 summer meeting.).

The impact of proposed changes in liver allocation policy on cold ischemia times and organ transportation costs.

Changes to the liver allocation system have been proposed to decrease regional variation in access to liver transplant. It is unclear what impact these changes will have on cold ischemia times (CITs) and donor transportation costs. Therefore, we performed a retrospective single center study (2008-2012) measuring liver procurement CIT and transportation costs. Four groups were defined: Local-within driving distance (Local-D, n = 262), Local-flight (Local-F, n = 105), Regional-flight <3 h (Regional <3 h, n = 61) and Regional-Flight >3 h (Regional >3 h, n = 53). The median travel distance increased in each group, varying from zero miles (Local-D), 196 miles (Local-F), 384 miles (Regional <3 h), to 1647 miles (Regional >3 h). Increasing travel distances did not significantly increase CIT until the flight time was >3 h. The average CIT ranged from 5.0 to 6.0 h for Local-D, Local-F and Regional <3 h, but increased to 10 h for Regional >3 h (p < 0.0001). Transportation costs increased with greater distance traveled: Local-D $101, Local-F $1993, Regional <3 h $8324 and Regional >3 h $27 810 (p < 0.0001). With proposed redistricting, local financial modeling suggests that the average liver donor procurement transportation variable direct costs will increase from $2415 to $7547/liver donor, an increase of 313%. These findings suggest that further discussion among transplant centers and insurance providers is needed prior to policy implementation.

Numerical study of the most stable contact angle of drops on tilted surfaces.

We present results for the most stable contact angle using a numerical implementation of the tilting plate method of Montes et al. (Montes Ruiz-Cabello, F. J.; Rodriguez-Valverde, M. A.; Cabrerizo-Vilchez, M. Soft Matter 2011, 7, 10457-10461). Comparison with the experimental results is made, obtaining a good agreement in most situations. In addition, the evolution of the contact angles of a tilted drop with a fixed circular line is analyzed. This analysis allows one to theoretically predict the most stable contact angle for tilted drops.

Multiple endosymbiont infections and reproductive manipulations in a linyphiid spider population.

In many arthropods, maternally inherited endosymbiotic bacteria can increase infection frequency by manipulating host reproduction. Multiple infections of different bacteria in a single host population are common, yet few studies have documented concurrent endosymbiont phenotypes or explored their potential interactions. We hypothesized that spiders might be a particularly useful taxon for investigating endosymbiont interactions, because they are host to a plethora of endosymbiotic bacteria and frequently exhibit multiple infections. We established two matrilines from the same population of the linyphiid spider Mermessus fradeorum and then used antibiotic curing and controlled mating assays to demonstrate that each matriline was subject to a distinct endosymbiotic reproductive manipulation. One matriline was co-infected with Rickettsia and Wolbachia and produced offspring with a radical female bias. Antibiotic treatment eliminated both endosymbionts and restored an even sex ratio to subsequent generations. Chromosomal and fecundity observations suggest a feminization mechanism. In the other matriline, a separate factorial mating assay of cured and infected spiders demonstrated strong cytoplasmic incompatibility (CI) induced by a different strain of Wolbachia. However, males with this Wolbachia induced only mild CI when mated with the Rickettsia-Wolbachia females. In a subsequent survey of a field population of M. fradeorum, we detected these same three endosymbionts infecting 55% of the spiders in almost all possible combinations, with nearly half of the infected spiders exhibiting multiple infection. Our results suggest that a dynamic network of endosymbionts may interact both within multiply infected hosts and within a population subject to multiple strong reproductive manipulations.

2013 European guideline on the management of lymphogranuloma venereum.

WHAT IS NEW IN THIS UPDATED GUIDELINE?: This is the update version of the 2010 European guideline on the management of lymphogranuloma venereum (LGV). New issues are: EPIDEMIOLOGY: Based on clonal relatedness of prevalent LGV strains there is evidence that the LGV epidemic among men who have sex with men (MSM) in the Western world prevailed already in the United States in the 1980s and was introduced into Europe by the end of the last century. AETIOLOGY AND TRANSMISSION: A new LGV variant causing severe proctitis was unveiled and designated L2c. The L2b LGV variant causing the vast majority of infections among MSM is now also found among a few heterosexual women. MANAGEMENT: Apart from HIV and STI screening, Hepatitis C Virus (HCV) testing should be offered to all LGV patients. To exclude reinfections, STI screening during a follow-up visit 3 months after an LGV diagnosis should be offered.

Risk factors for rectal lymphogranuloma venereum in gay men: results of a multicentre case-control study in the U.K.

OBJECTIVE: To identify risk factors for rectal lymphogranuloma venereum (rLGV) in men who have sex with men (MSM). DESIGN: A case-control study at 6 U.K. hospitals compared MSM with rLGV (cases) with rLGV-negative controls: MSM without potential rLGV symptoms (CGa) and separately, MSM with such symptoms (CGs). METHODS: Between 2008 and 2010, there were 90 rLGV cases, 74 CGa and 69 CGs recruited. Lifestyles and sexual behaviours in the previous 3 months were reported using internet-based computer-assisted self-interviews. Logistic regression was used to investigate factors associated with rLGV. RESULTS: Cases were significantly more likely to be HIV-positive (89%) compared with CGa (46%) and CGs (64%). Independent behavioural risks for rLGV were: unprotected receptive anal intercourse (adjusted OR (AOR)10.7, 95% CI 3.5 to 32.8), fisting another (AOR=6.7, CI 1.8 to 25.3), sex under the influence of gamma-hydroxybutyrate (AOR=3.1, CI 1.3 to 7.4) and anonymous sexual contacts (AOR=2.7, CI 1.2 to 6.3), compared with CGa; unprotected insertive anal intercourse (AOR=4.7, CI 2.0 to 10.9) and rectal douching (AOR=2.9 CI 1.3 to 6.6), compared with CGs. An incubation period from exposure to symptoms of 30 days was indicated. CONCLUSIONS: Unprotected receptive anal intercourse is a key risk factor for rectal LGV with the likelihood that rectal-to-rectal transmission is facilitated where insertive anal sex also occurs. The association between HIV and rLGV appears linked to HIV-positive men seeking unprotected sex with others with the same HIV status, sexual and drug interests. Such men should be targeted for frequent STI screening and interventions to minimise associated risks.

Recreational drug use in men who have sex with men (MSM) attending UK sexual health services is significantly higher than in non-MSM.

INTRODUCTION: The aim of this study was to investigate the pattern of recreational drug use in patients attending a genitourinary medicine clinic, and to determine whether drug use was greater among men who have sex with men (MSM) patients, when compared to non-MSM male patients. METHODS: A questionnaire was given to all patients attending the genitourinary medicine clinics at two inner city teaching hospitals over 3 months (July to September 2011). The questionnaire was self-completed by patients while waiting to be seen by a clinician. Data were collected on age, gender, gender of sexual partner(s), and previous/current recreational drug use (type/frequency of drugs used). Only data from male respondents have been analysed in this paper. RESULTS: 1328 questionnaires were completed. Of the male respondents (n=729), 475 (65.2%) were identified as non-MSM and 254 (34.8%) were identified as MSM. The mean ± SD age of male respondents was 31 ± 9 years years. Lifetime and last month use of mephedrone, ketamine, volatile nitrites ('poppers'), sildenafil (Viagra), GHB, and GBL were all significantly higher in the MSM group compared to the non-MSM group. Lifetime use of cocaine powder, MDMA, amphetamine, and methamphetamine were also significantly higher in the MSM group; however, there was no significant difference in last month use of these drugs between MSM and non-MSM groups. CONCLUSIONS: Both lifetime and last month use of most recreational drugs was more common in MSM, when compared to non-MSM males. Sexual health clinics may provide an opportunistic encounter to identify patterns of recreational drug use, explore motivations for use, and implement strategies to reduce harms related to drug use. This will require a multidisciplinary approach to address the psychosocial aspects of drug taking behaviours, in combination with healthcare professionals experienced in the management of recreational drug use.

A novel design solution to the fraenal notch of maxillary dentures.

This study investigates a novel design feature for the fraenal notch of maxillary dentures, using computational and experimental methods, and shows that its use could significantly increase the longevity of the prosthesis. A two-step process can be used to create the design feature with current denture base materials, but would be highly dependent on the individual skill of the dental technician. Therefore, an alternative form of manufacture, multi-material additive layer manufacture (or '3D printing'), has been proposed as a future method for the direct production of complete dentures with multi-material design features.

Performance of the GeneXpert CT/NG assay compared to that of the Aptima AC2 assay for detection of rectal Chlamydia trachomatis and Neisseria gonorrhoeae by use of residual Aptima Samples.

There are currently no commercially available molecular assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in rectal swabs with regulatory approval. We compared the Cepheid GeneXpert CT/NG assay with the GenProbe Aptima Combo2 assay, using 409 rectal swabs. Using Aptima as the gold standard, the sensitivity, specificity, and positive and negative predictive values of GeneXpert for the detection of C. trachomatis and N. gonorrhoeae were 86%, 99.2%, 92.5%, and 98.4% and 91.1%, 100%, 100%, and 98.6%, respectively. Despite significant dilution of samples prior to GeneXpert testing, the assay performed well with excellent specificity.

Simulation analysis of contact angles and retention forces of liquid drops on inclined surfaces.

A simulation study of liquid drops on inclined surfaces is performed in order to understand the evolution of drop shapes, contact angles, and retention forces with the tilt angle. The simulations are made by means of a method recently developed for dealing with contact angle hysteresis in the public-domain Surface Evolver software. The results of our simulations are highly dependent on the initial contact angle of the drop. For a drop with an initial contact angle equal to the advancing angle, we obtain results similar to those of experiments in which a drop is placed on a horizontal surface that is slowly tilted. For drops with an initial contact angle equal to the mean between the advancing and the receding contact angles, we recover previous results of finite element studies of drops on inclined surfaces. Comparison with experimental results for molten Sn-Ag-Cu on a tilted Cu substrate shows excellent agreement.

Success versus failure: Efficient heat devices in thermodynamics.

Classical equilibrium thermodynamics provides, in a general way, upper Carnot bounds for the performance of energy converters. Nevertheless, to suggest lower bounds is a much more subtle issue, especially when they are related to a definition of convenience. Here, this issue is investigated in a unified way for heat engines, refrigerators, and heat pumps. First, irreversibilities are weighted in the context of heat reservoir stability for irreversible engines by using the thermodynamic distance between minimum energy and maximum entropy steady states. Some stability coefficients can be related to a majorization process and the obtention of Pareto fronts, linking stability and optimization by means of efficiency and entropy due to correlations between system and reservoirs. Second, these findings are interpreted in a very simple context. A region where the heat device is efficient is defined in a general scheme and, below this zone, the heat device is inefficient in the sense that irreversibilities somehow dominate its behavior. These findings allow for a clearer understanding of the role played by some well-known figures of merit in the scope of finite-time and -size optimization. Comparison with experimental results is provided.

Theory and simulation of angular hysteresis on planar surfaces.

A simple model is proposed to simulate contact angle hysteresis in drops on a planar surface. The model is based on assuming a friction force acting on the triple contact line in such a way that the contact line keeps fixed for contact angles comprised between the advancing angle and the receding one and is allowed to move in order to avoid angles outside this interval. The model is straightforwardly applied to axisymmetric drops for which a simple solution of the Young-Laplace equation can be obtained. A variation of the method has also been implemented for nonaxisymmetric drops by resorting to the public-domain "Surface Evolver" software. Comparison with experiments shows the excellent performance of the model.

Endosymbiont costs and benefits in a parasitoid infected with both Wolbachia and Cardinium.

Theory suggests that maternally inherited endosymbionts can promote their spread and persistence in host populations by enhancing the production of daughters by infected hosts, either by improving overall host fitness, or through reproductive manipulation. In the doubly infected parasitoid wasp Encarsia inaron, Wolbachia manipulates host reproduction through cytoplasmic incompatibility (CI), but Cardinium does not. We investigated the fitness costs and/or benefits of infection by each bacterium in differentially cured E. inaron as a potential explanation for persistence of Cardinium in this population. We introgressed lines infected with Wolbachia, Cardinium or both with the cured line to create a similar genetic background, and evaluated several parasitoid fitness parameters. We found that symbiont infection resulted in both fitness costs and benefits for E. inaron. The cost was lower initial egg load for all infected wasps. The benefit was increased survivorship, which in turn increased male production for wasps infected with only Cardinium. Female production was unaffected by symbiont infection; we therefore have not yet identified a causal fitness effect that can explain the persistence of Cardinium in the population. Interestingly, the Cardinium survivorship benefit was not evident when Wolbachia was also present in the host, and the reproduction of doubly infected individuals did not differ significantly from uninfected wasps. Therefore, the results of our study show that even when multiple infections seem to have no effect on a host, there may be a complex interaction of costs and benefits among symbionts.

Entropic selectivity of binary mixtures in cylindrical pores.

We show that a simple model consisting of a binary hard-sphere mixture in a narrow cylindrical pore can lead to strong size selectivity by considering a situation where each species of the mixture sees a different radius of the cylinder. Two mechanisms are proposed to explain the observed results depending on the radius of the cylinder: for large radii the selectivity is driven by an enhancement of the depletion forces at the cylinder walls whereas for the narrowest cylinders excluded-volume effects lead to a shift of the effective chemical potential of the particles in the pore.

Experiences of workplace bullying among academics in a health sciences faculty at a South African university.

BACKGROUND: Workplace bullying and other negative workplace behaviours are problems that need to be addressed across many work settings, including at universities. OBJECTIVES: To examine the prevalence of bullying among academics, and factors associated with bullying, in a faculty of health sciences (FHS) of a South African university. METHODS: All academic staff, except senior managers, were invited to participate by completing a self-administered, web-based questionnaire hosted on REDCap. In adition to sociodemographic information, the survey collected information on bullying, and the factors associated with experiences of workplace bullying. Survey data were exported to Stata 13 for analysis. The data were weighted to take account of the distribution of staff in the FHS. Chi-square tests and a multiple logistic regression model for bullying were utilised. RESULTS: The majority of study participants were white (52%), female (70%) and South African (85%). Bullying in the workplace was experienced by 58% of respondents, of whom 44% experienced bullying more than once, and 64% of participants had witnessed bullying. Being female (adjusted odds ratio (aOR) 1.83; 95% confidence interval (CI) 1.14 - 2.93; p<0.05) and being jointly appointed as both a clinician in a health facility and an academic in the university (aOR 1.73; 95% CI 1.29 - 2.32; p<0.001) increased the odds of experiencing workplace bullying. CONCLUSIONS: A combination of strategies is needed, including clear FHS policies to prevent bullying, training in bullying prevention and critical diversity, and positive practice environments.

Canine CYP2B11 metabolizes and is inhibited by anesthetic agents often co-administered in dogs.

Medetomidine is a well-established sedative and analgesic for dogs and cats. As a premedicant for anesthesia regimens that also include other agents, medetomidine can also provide a dose-sparing effect. While there are likely several reasons for the dose-sparing effect of medetomidine, the role of metabolic drug-drug interactions at the single enzyme level has not yet been examined. Using a panel of individually expressed canine cytochromes P450 cloned from beagle liver, this report demonstrates that medetomidine is an extremely potent CYP2B11 inhibitor (IC(50) < 10 nm) and that ketamine and midazolam are CYP2B11 substrates with high intrinsic clearances. These in vitro findings suggest that under some circumstances, medetomidine (i.e. 'perpetrator') may inhibit the metabolic clearance of some high metabolic clearance drugs (i.e. 'victims') with which it is commonly co-administered via the CYP2B11 pathway. However, as the dose-sparing effect of medetomidine premedication commonly results in anesthetic dose reduction, any increased plasma concentrations of victim drugs caused by medetomidine would still be lower than if no dose reduction had been made. Further studies are needed to characterize whether medetomidine possesses the potential to cause pharmacokinetic interactions. In conclusion, the ability of recombinant P450s to define canine-specific drug clearance pathways and P450 inhibitors should prove useful in identifying drug combinations that may require dose adjustments in dogs.

Distribution, metabolism, and excretion of toceranib phosphate (Palladia, SU11654), a novel tyrosine kinase inhibitor, in dogs.

Toceranib phosphate (Palladia, SU11654), a multireceptor tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activity, has been developed for the treatment of mast cell tumors in dogs. An overview of the distribution, metabolism, and excretion of toceranib phosphate in dogs is presented. When [(14)C]-toceranib was orally administered to dogs, the majority of the radioactivity (92%) was excreted in feces and only a small portion (7%) was excreted in urine. Seven days after a single 3.25 mg/kg oral dose, radioactivity was the highest in bile and liver, with measurable concentrations in lymph nodes, colon, adrenals, bone marrow, kidneys, lungs, spleen, pancreas, and skin. Plasma protein binding of toceranib in fresh plasma ranged from 90.8% to 92.8% at concentrations between 20 ng/mL and 500 ng/mL and was independent of concentration. Microsomal and hepatocyte incubations resulted in the formation of a single metabolite. Spectrometric analysis of the metabolite was consistent with the formation of an alicyclic N-oxide of toceranib. The combination of the high rate of fecal excretion and the long elimination half-life of toceranib indicate enterohepatic recirculation of the parent compound and/or the N-oxide metabolite.