Meatal Swabs Contain Less Cellular Material and Are Associated with a Decrease in Gram Stain Smear Quality Compared to Urethral Swabs in Men

Urethral swabs are the samples of choice for point-of-care Gram stain testing to diagnose Neisseria gonorrhoeae infection and nongonococcal urethritis (NGU) in men. As an alternative to urethral swabs, meatal swabs have been recommended for the collection of urethral discharge to diagnose N. gonorrhoeae and Chlamydia trachomatis infection in certain populations by nucleic acid amplification testing (NAAT), as they involve a less invasive collection method. However, as meatal swabs could be sampling a reduced surface area and result in fewer collected epithelial cells compared to urethral swabs, the adequacy of meatal swab specimens to collect sufficient cellular material for Gram stain testing remains unknown. We enrolled 66 men who underwent either urethral or meatal swabbing and compared the cellular content and Gram stain failure rate. We measured the difference in swab cellular content using the Cepheid Xpert CT/NG sample adequacy control crossing threshold (SACCT) and determined the failure rate of Gram stain smears (GSS) due to insufficient cellular material. In the absence of discharge, meatal smears were associated with a significant reduction in cellular content (P = 0.0118), which corresponded with a GSS failure rate significantly higher than that for urethral swabs (45% versus 3%, respectively; P < 0.0001). When discharge was present, there was no difference among results from urethral and meatal swabs. Therefore, if GSS testing is being considered for point-of-care diagnosis of N. gonorrhoeae infection or NGU in men, meatal swabs should be avoided in the absence of a visible discharge

Delay in Seeking Healthcare Services Following Onset of Urethritis Symptoms in Men

Background: Symptom awareness, behavioral factors, and other barriers associated with timely sexually transmitted infection (STI) health care provision in men is not well studied. Methods: Men attending an STI clinic answered a questionnaire regarding their symptoms, sexual behavior, and sociodemographic and behavioral characteristics. Characteristics of symptomatic men were compared between those who did and did not delay seeking health care services. Delayed care seeking was defined as clinic attendance longer than 7 days after symptoms, whereas early care seeking was defined as clinic attendance of 7 days or less. Results: Over a quarter (n = 43 [27.7%]) of men with urethritis symptoms (urethral discharge or dysuria) delayed seeking care for more than 7 days. Compared with men who sought treatment within 7 days, those that delayed care worried for longer periods that their symptoms were STI-related, were more likely to attempt self-treatment of STI symptoms, were more likely to continue engaging in sexual activity, and were less likely to use a condom during their last sexual encounter. Conversely, men that delayed care seeking were less likely to have urethral discharge on physical examination, to have 5 or more polymorphonuclear leukocytes, and to test positive for Neisseria gonorrhoeae. When compared with men that sought care earlier, men that delayed care seeking had fewer overall and new partners in the past 30 days. Conclusions: Our data suggest that over a quarter of men aware of STI symptoms delay seeking health services. Interventions that promote better patient understanding of the importance of symptom recognition and that facilitate timely access to care may provide new opportunities to reduce STI transmission

Defining the Urethritis Syndrome in Men Using Patient Reported Symptoms

To evaluate self-reported symptoms to guide urethritis diagnosis, symptomatic men being evaluated for urethritis were asked about seven symptoms captured during history-taking. Discharge and dysuria were significantly associated with urethritis and, when combined with genital irritation and itching, identified 95% of urethritis cases; odor and urinary frequency performed poorly

The fishes of ascension Island, central Atlantic Ocean - new records and an annotated checklist

A checklist of the fishes of Ascension Island is presented. The species Rhincodon typus, Alopias superciliosus, Isurus oxyrinchus, Carcharhinus obscurus, Galeocerdo cuvier, Sphyrna lewini, Hexanchus griseus, Manta birostris, Gymnothorax vicinus, Hippocampus sp., Epinephelus itajara, Cookeolus japonicus, Apogon pseudomaculatus, Phaeoptyx pigmentaria, Remora albescens, Caranx bartholomaei, Carangoides ruber, Decapterus tabl, Seriola dumerili, Thalassoma sanctaehelenae, Cryptotomus sp., Ruvettus pretiosus, Acanthocybium solandri, Auxis rochei, Auxis thazard, Euthynnus alletteratus, Katsuwonus pelamis, Thunnus alalunga, Thunnus obesus, Xiphias gladius, Istiophorus platypterus, Kajikia albida, Makaira nigricans, Tetrapturus pfluegeri, Hyperoglyphe perciformis, Schedophilus sp., Cantherhines macrocerus, Sphoeroides pachygaster and Diodon eydouxii are recorded for the first time from Ascension Island. We have recognized two previous records as identification errors and indicate 11 other records as doubtful. Including the 40 new records, we now list 173 fish species from Ascension Island, of which 133 might be considered 'coastal fish species'. Eleven of these (8.3%) appear to be endemic to the island and a further 16 species (12%) appear to be shared endemics with St Helena Island.Darwin Initiative [EIDCF012]info:eu-repo/semantics/publishedVersio

Are we over-treating with checkpoint inhibitors?

Anti-PD-1 antibodies offer potentially life-saving treatment for some cancer patients, but their chronic administration generates high and ever-increasing costs. Despite licensing for long-term use, optimal treatment duration is unknown. We challenge the need for long-term treatment duration, using evidence from melanoma research, both published and in process

Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans

More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein α-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associ

The DANTE trial protocol: a randomised phase III trial to evaluate the Duration of ANti-PD-1 monoclonal antibody Treatment in patients with metastatic mElanoma.

BACKGROUND: Immunotherapy is revolutionising the treatment of patients diagnosed with melanoma and other cancers. The first immune checkpoint inhibitor, ipilimumab (targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)), showed a survival advantage over standard chemotherapy. Subsequently the anti-programmed cell death protein 1 (PD-1) antibodies, nivolumab and pembrolizumab were shown to be more effective than ipilimumab. Ipilimumab combined with nivolumab gives an incremental gain in overall survival compared with nivolumab alone but increases the risk of severe, potentially life-threatening toxicities. In contrast to ipilimumab monotherapy, anti-PD-1 antibodies are licensed to be continued until disease progression. Follow-up of patients recruited to the first trials evaluating 2 years of pembrolizumab showed that three-quarters of responding patients continue responding after stopping treatment. Suggestive of early response, we hypothesised that continuing anti-PD-1 treatment beyond 1 year in progression-free patients may be unnecessary and so designed the DANTE trial. METHODS: DANTE is a multicentre, randomised, phase III, non-inferiority trial to evaluate the duration of anti-PD-1 therapy in patients with metastatic (unresectable stage III and stage IV) melanoma. It uses a two-stage recruitment strategy, registering patients before they complete 1 year of first-line anti-PD-1 +/- CTLA-4 therapy and randomising eligible patients who have received 12 months of treatment and are progression-free at 1 year. At randomisation, 1208 patients are assigned (1:1) to either 1) continue anti-PD-1 treatment until disease progression/ unacceptable toxicity/ for at least 2 years in the absence of disease progression/ unacceptable toxicity or 2) to stop treatment. Randomisation stratifies for baseline prognostic factors. The primary outcome is progression-free survival at 3, 6, 9 and 12 months and then, 6-monthly for up to 4-years. Secondary outcomes collected at all timepoints include overall survival, response-rate and duration and safety, with quality of life and cost-effectiveness outcomes collected 3-monthly for up to 18-months. Sub-studies include a qualitative analysis of patient acceptance of randomisation and sample collection to inform future translational studies into response/ toxicity biomarkers. DISCUSSION: DANTE is a unique prospective trial investigating the optimal duration of anti-PD-1 therapy in metastatic melanoma patients. Outcomes will inform future use of these high burden drugs. TRIAL REGISTRATION: ISRCTN15837212 , 31 July 2018

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial

Background: Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer. Methods: In this phase 3 trial, women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC–IV epithelial ovarian cancer were randomly assigned to group 1 (carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 and 80 mg/m2 paclitaxel weekly). Written informed consent was provided by all women who entered the trial. The protocol had the appropriate national research ethics committee approval for the countries where the study was conducted. Patients entered the trial after immediate primary surgery, or before neoadjuvant chemotherapy with subsequent planned delayed primary surgery. The trial coprimary outcomes were progression-free survival and overall survival. Data analyses were done on an intention-to-treat basis, and were powered to detect a hazard ratio of 0·75 in progression-free survival. The main comparisons were between the control group (group 1) and each of the weekly research groups (groups 2 and 3). Findings: Between June 6, 2011, and Nov 28, 2014, 1566 women were randomly assigned to treatment. 72% (365), completed six protocol-defined treatment cycles in group 1, 60% (305) in group 2, and 63% (322) in group 3, although 90% (454), 89% (454), and 85% (437) completed six platinum-based chemotherapy cycles, respectively. Paclitaxel dose intensification was achieved with weekly treatment (median total paclitaxel dose 1010 mg/m2 in group 1; 1233 mg/m2 in group 2; 1274 mg/m2 in group 3). By February, 2017, 1018 (65%) patients had experienced disease progression. No significant progression-free survival increase was observed with either weekly regimen (restricted mean survival time 24·4 months [97·5% CI 23·0–26·0] in group 1, 24·9 months [24·0–25·9] in group 2, 25·3 months [23·9–26·9] in group 3; median progression-free survival 17·7 months [IQR 10·6–not reached] in group 1, 20·8 months [11·9–59·0] in group 2, 21·0 months [12·0–54·0] in group 3; log-rank p=0·35 for group 2 vs group 1; group 3 vs 1 p=0·51). Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated. Febrile neutropenia and sensory neuropathy incidences were similar across groups. Interpretation Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve progression-free survival compared with standard 3-weekly chemotherapy in predominantly European populations. Funding: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, Cancer Australia

Constraining the radio jet proper motion of the high-redshift quasar J2134-0419 at z = 4.3

To date, PMN J2134-0419 (at a redshift z = 4.33) is the second most distant quasar known with a milliarcsecond-scale morphology permitting direct estimates of the jet proper motion. Based on two-epoch observations, we constrained its radio jet proper motion using the very long baseline interferometry (VLBI) technique. The observations were conducted with the European VLBI Network (EVN) at 5 GHz on 1999 November 26 and 2015 October 6. We imaged the central 10-pc scale radio jet emission and modeled its brightness distribution. By identifying a jet component at both epochs separated by 15.86 yr, a proper motion of μ = 0.035 ± 0.023 mas yr-1 is found. It corresponds to an apparent superluminal speed of βa = 4.1 ± 2.7 c. Relativistic beaming at both epochs suggests that the jet viewing angle with respect to the line of sight is smaller than 20°, with a minimum bulk Lorentz factor Γ = 4.3. The small value of the proper motion is in good agreement with the expectations from the cosmological interpretation of the redshift and the current cosmological model. Additionally we analyzed archival Very Large Array observations of J2143-0419 and found indication of a bent jet extending to ˜30 kpc