Unsteady turbulence in a tidal bore: field measurements in the Garonne River in October 2013

A tidal bore is an unsteady rapidly-varied free-surface flow generated by the rapid rise in water elevation during the early flood tide, when the tidal range exceeds 4.5 to 6 m and the channel bathymetry amplifies the flood tidal wave. This study describes a detailed field investigation conducted in the Garonne River (France). The tidal bore was undular on 19 October 2013 and the bore front was followed by some well-defined whelps. The instantaneous velocity data indicated large and rapid fluctuations of all velocity components during the tidal bore. Large Reynolds shear stresses were observed during and after the tidal bore passage. Altogether the investigation characterised some unusual turbulence transient in a large river system

Dynamics and Deposition of Sediment-Bearing Multi- Pulsed Flows and Geological Implication

Copyright © 2019, SEPM (Society for Sedimentary Geology) Previous studies on dilute, multi-pulsed, subaqueous saline flows have demonstrated that pulses will inevitably advect forwards to merge with the flow front. On the assumption that pulse merging occurs in natural-scale turbidity currents, it was suggested that multi-pulsed turbidites that display vertical cycles of coarsening and fining would transition laterally to single-pulsed, normally graded turbidites beyond the point of pulse merging. In this study, experiments of dilute, single- and multi-pulsed sediment-bearing flows (turbidity currents) are conducted to test the linkages between downstream flow evolution and associated deposit structure. Experimental data confirm that pulse merging occurs in laboratory-scale turbidity currents. However, only a weak correspondence was seen between longitudinal variations in the internal flow dynamics and the vertical structure of deposits; multi-pulsed deposits were documented, but transitioned to single-pulsed deposits before the pulse merging point. This early transition is attributed to rapid sedimentation-related depletion of the coarser-grained suspended fraction in the laboratory setting, whose absence may have prevented the distal development of multi-pulsed deposits; this factor complicates estimation of the transition point in natural-scale turbidite systems

Dynamics and deposition of sediment-bearing multi-pulsed flows and geological implication

Previous studies on dilute, multi-pulsed, subaqueous saline flows have demonstrated that pulses will inevitably advect forwards to merge with the flow front. On the assumption that pulse merging occurs in natural-scale turbidity currents, it was suggested that multi-pulsed turbidites that display vertical cycles of coarsening and fining would transition laterally to single-pulsed, normally graded turbidites beyond the point of pulse merging. In this study, experiments of dilute, single- and multi-pulsed sediment-bearing flows (turbidity currents) are conducted to test the linkages between downstream flow evolution and associated deposit structure. Experimental data confirm that pulse merging occurs in laboratory-scale turbidity currents. However, only a weak correspondence was seen between longitudinal variations in the internal flow dynamics and the vertical structure of deposits; multi-pulsed deposits were documented, but transitioned to single-pulsed deposits before the pulse merging point. This early transition is attributed to rapid sedimentation-related depletion of the coarser-grained suspended fraction in the laboratory setting, whose absence may have prevented the distal development of multi-pulsed deposits; this factor complicates estimation of the transition point in natural-scale turbidite systems

NICE guidance on sepsis is of limited value in postoperative colorectal patients: the scores that cry ‘wolf!’

Background and aimsLate recognition of sepsis and consequent death remains a problem. To address this, the National Institute for Health and Care Excellence has published updated guidance recommending the use of the Quick Sequential Organ Failure Assessment (Q-SOFA) score when assessing patients at risk of sepsis following the publication of the Third International Consensus Definitions for Sepsis and Septic Shock. The trauma from major surgery produces a systemic inflammatory response syndrome (SIRS) postoperatively as part of its natural history, which may falsely trigger scoring systems. We aimed to assess the accuracy of Q-SOFA and SIRS criteria as recommended scores for early detection of sepsis and septic complications in the first 48hrs after colorectal cancer surgery.MethodsWe reviewed all elective major colorectal operations in a single centre during a 12-month period from prospectively maintained electronic records.ResultsOne hundred and thirty nine patients were included in this study. In all, 29 patients developed postoperative infective complications in hospital. Nineteen patients triggered on SIRS without developing infective complications, while 42 patients triggered on Q-SOFA with no infective complications. The area under the ROC curve was 0.52 for Q-SOFA and 0.67 for SIRS.DiscussionQ-SOFA appears to perform little better than a coin toss at identifying postoperative sepsis after colorectal cancer resection and is inferior to the SIRS criteria. More work is required to assess whether a combination of scoring criteria, biochemical markers and automated tools could increase accurate detection of postoperative infection and trigger early intervention

An oral lipidic native testosterone formulation that is absorbed independent of food

Context There is no licensed oral native testosterone (NT) because of challenges in the formulation. Licensed oral formulations of the ester, testosterone undecanoate (TU), require a meal for absorption and generate supraphysiological dihydrotestosterone (DHT) levels. Objective To develop an oral NT formulation. Design and methods A lipid-based formulation of native testosterone filled into soft-gelatin capsules at 40 mg per capsule was designed with 2 years of stability at ambient temperature. Pharmacokinetic comparison studies of this oral lipidic NT formulation to oral TU were conducted in dogs and hypogonadal men. Results In dogs, 40 mg NT was well absorbed under fasted conditions whereas 40 mg TU required a high-fat meal: for NT, the mean fed/fasted AUC ratio was 1.63 and for TU 7.05. In hypogonadal men, fed and fasted NT had similar pharmacokinetics: Cmax mean 26.5 vs 30.4 nmol/L (769 vs 882 ng/dL), AUC0–10 h 87 vs 88.6 h nmol/L. NT (fed state) showed a testosterone AUC increase of 45% between 120 and 200 mg, and NT 200 mg gave a similar mean AUC0–10 h to TU 80 mg: 87 vs 64.8 h nmol/L. Serum TU levels were variable and on a molar basis were ~ten-fold higher than serum testosterone levels after TU 80 mg fed. The DHT: testosterone AUC0–10 h ratio was more physiological for NT than TU being 0.19 vs 0.36. There were no emerging safety concerns with NT. Conclusion This novel oral lipidic native testosterone formulation has potential advantages over oral TU of dosing independently of food and a lower risk of supraphysiological DHT levels. Significance statement There is no licensed oral testosterone because of challenges in formulation, and the oral formulations of the ester, testosterone undecanoate, require a fatty meal for absorption and generate supraphysiological dihydrotestosterone levels. We have overcome the design challenges and formulated an oral native testosterone that can be taken with or without food and provides physiological levels of testosterone and dihydrotestosterone in hypogonadal men. This formulation, DITEST, has the potential advantage of being oral for patients who do not tolerate injections and less risk of adverse events that might theoretically be associated with elevated dihydrotestosterone levels. Future studies will need to define the dosing regimen for replacement in hypogonadal men

Constitutively active follicle-stimulating hormone receptor enables androgen-independent spermatogenesis

Spermatogenesis is regulated by the 2 pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This process is considered impossible without the absolute requirement of LH-stimulated testicular testosterone (T) production. The role of FSH remains unclear because men and mice with inactivating FSH receptor (FSHR) mutations are fertile. We revisited the role of FSH in spermatogenesis using transgenic mice expressing a constitutively strongly active FSHR mutant in a LH receptor-null (LHR-null) background. The mutant FSHR reversed the azoospermia and partially restored fertility of Lhr(-/-) mice. The finding was initially ascribed to the residual Leydig cell T production. However, when T action was completely blocked with the potent antiandrogen flutamide, spermatogenesis persisted. Hence, completely T-independent spermatogenesis is possible through strong FSHR activation, and the dogma of T being a sine qua non for spermatogenesis may need modification. The mechanism for the finding appeared to be that FSHR activation maintained the expression of Sertoli cell genes considered androgen dependent. The translational message of our findings is the possibility of developing a new strategy of high-dose FSH treatment for spermatogenic failure. Our findings also provide an explanation of molecular pathogenesis for Pasqualini syndrome (fertile eunuchs; LH/T deficiency with persistent spermatogenesis) and explain how the hormonal regulation of spermatogenesis has shifted from FSH to T dominance during evolution

The androgen receptor gene CAG repeat in relation to 4-year changes in androgen-sensitive endpoints in community-dwelling older European men

Context: The Androgen Receptor (AR) gene exon 1 CAG repeat length has been proposed to be a determinant of between-individual variations in androgen action in target tissues, which might regulate phenotypic differences of human ageing. However, findings on its phenotypic effects are inconclusive.Objective: To assess whether the AR CAG repeat length is associated with longitudinal changes in endpoints which are influenced by testosterone (T) levels in middle-aged and elderly European men.Design: Multinational European observational prospective cohort studyParticipants: 1887 men (mean±sd age: 63±11 years; median follow-up: 4.3 years) from centres of 8 European countries comprised the analysis sample after exclusion of those with diagnosed diseases of the hypothalamic-pituitary-testicular (HPT) axis.Main outcome measures: Longitudinal associations between the AR CAG repeat and changes in androgen-sensitive endpoints (ASEs) and medical conditions were assessed using regression analysis adjusting for age and centre. The AR CAG repeat length was treated both as a continuous and categorical (6-20; 21-23; 24-39 repeats) predictor. Additional analysis investigated whether results were independent of baseline T or oestradiol (E2) levels.Results: The AR CAG repeat, when used as a continuous or categorical predictor, was not associated with longitudinal changes in ASEs or medical conditions after adjustments. These results were independent of T and E2 levels.Conclusion: Within a 4-year timeframe, variations in the AR CAG repeat do not contribute to the rate of phenotypic ageing, over and above, that, which might be associated with the age-related decline in T levels

Development of a UK core dataset for geriatric medicine research: a position statement and results from a Delphi consensus process

BACKGROUND: There is lack of standardisation in assessment tools used in geriatric medicine research, which makes pooling of data and cross-study comparisons difficult. METHODS: We conducted a modified Delphi process to establish measures to be included within core and extended datasets for geriatric medicine research in the United Kingdom (UK). This included three complete questionnaire rounds, and one consensus meeting. Participants were selected from attendance at the NIHR Newcastle Biomedical Research Centre meeting, May 2019, and academic geriatric medicine e-mailing lists. Literature review was used to develop the initial questionnaire, with all responses then included in the second questionnaire. The third questionnaire used refined options from the second questionnaire with response ranking. RESULTS: Ninety-eight responses were obtained across all questionnaire rounds (Initial: 19, Second: 21, Third: 58) from experienced and early career researchers in geriatric medicine. The initial questionnaire included 18 questions with short text responses, including one question for responders to suggest additional items. Twenty-six questions were included in the second questionnaire, with 108 within category options. The third questionnaire included three ranking, seven final agreement, and four binary option questions. Results were discussed at the consensus meeting. In our position statement, the final consensus dataset includes six core domains: demographics (age, gender, ethnicity, socioeconomic status), specified morbidities, functional ability (Barthel and/or Nottingham Extended Activities of Daily Living), Clinical Frailty Scale (CFS), cognition, and patient-reported outcome measures (dependent on research question). We also propose how additional variables should be measured within an extended dataset. CONCLUSIONS: Our core and extended datasets represent current consensus opinion of academic geriatric medicine clinicians across the UK. We consider the development and further use of these datasets will strengthen collaboration between researchers and academic institutions

Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Context: Salivary T (Sal-T) measurement by liquid chromatography–tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey. Objective: This study sought to examine associations between Sal-T and health-related factors in men and women age 18 –74 years. Design and Setting: Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview. Participants: Study participants included 1599 men and 2123 women. Methods: Sal-T was measured using liquid chromatography–tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T. Results: In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for healthrelated factors. In women, Sal-T declined with increasing age; however, there were no age-independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers. Conclusions: Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research