Eurycea wilderae

Number of Pages: 4Integrative BiologyGeological Science

Ultrastructure of the reproductive system of the black swamp snake (\u3ci\u3eSeminatrix pygaea\u3c/i\u3e). Part III. The sexual segment of the male kidney.

In mature male snakes and lizards, a distal portion of the nephron is hypertrophied in relation to its appearance in females and immature males. This sexual segment of the male kidney apparently provides seminal fluid that is mixed with sperm and released into the female cloaca during copulation. In this article, we provide the first study at the ultrastructural level of seasonal variation in the sexual segment of the kidney of a squamate, the natricine snake Seminatrix pygaea. Previous workers have indicated that the sexual segment is secretory only when the testes are spermatogenically active. The sexual segment of the kidney in S. pygaea does not go through an extended period of inactivity but does show a cycle of synthesis and secretion that can be related to the spermatogenic cycle and mating activity. We show that synthesis of secretory product is initiated with the onset of spermatogenic activity in the spring and culminates with completion of spermiation in the fall. Secretion of the product, however, occurs in a premating period in March when the testes are inactive. Secretion during this premating period is probably necessary to provide time for the passage of the products down the ureter in order to mix with spermduring mating later in spring

Eurycea junaluska

Number of Pages: 2Integrative BiologyGeological Science

Eurycea cirrigera

Number of Pages: 6Integrative BiologyGeological Science

Mechanochemical action of the dynamin protein

Dynamin is a ubiquitous GTPase that tubulates lipid bilayers and is implicated in many membrane severing processes in eukaryotic cells. Setting the grounds for a better understanding of this biological function, we develop a generalized hydrodynamics description of the conformational change of large dynamin-membrane tubes taking into account GTP consumption as a free energy source. On observable time scales, dissipation is dominated by an effective dynamin/membrane friction and the deformation field of the tube has a simple diffusive behavior, which could be tested experimentally. A more involved, semi-microscopic model yields complete predictions for the dynamics of the tube and possibly accounts for contradictory experimental results concerning its change of conformation as well as for plectonemic supercoiling.Comment: 17 pages, 4 figures; typos corrected, reference adde

Clean Time-Dependent String Backgrounds from Bubble Baths

We consider the set of controlled time-dependent backgrounds of general relativity and string theory describing ``bubbles of nothing'', obtained via double analytic continuation of black hole solutions. We analyze their quantum stability, uncover some novel features of their dynamics, identify their causal structure and observables, and compute their particle production spectrum. We present a general relation between squeezed states, such as those arising in cosmological particle creation, and nonlocal theories on the string worldsheet. The bubble backgrounds have various aspects in common with de Sitter space, Rindler space, and moving mirror systems, but constitute controlled solutions of general relativity and string theory with no external forces. They provide a useful theoretical laboratory for studying issues of observables in systems with cosmological horizons, particle creation, and time-dependent string perturbation theory.Comment: 38 pages, harvmac big, 6 figure

Prevention And Treatment of Hypertension With Algorithm-based therapy (PATHWAY) number 2: protocol for a randomised crossover trial to determine optimal treatment for drug-resistant hypertension.

This is the final published version. It first appeared at http://bmjopen.bmj.com/content/5/8/e008951.full.INTRODUCTION: Resistant hypertension is inadequately controlled blood pressure (BP) despite treatment with at least three BP-lowering drugs. A popular hypothesis is that resistant hypertension is due to excessive Na(+)-retention, and that 'further diuretic therapy' will be superior to alternative add-on drugs. METHODS AND ANALYSIS: Placebo-controlled, random crossover study of fourth-line treatment when added to standard (A+C+D) triple drug therapy: ACE inhibitor or Angiotensin receptor blocker (A) +Calcium channel blocker (C)+Diuretic (D). Patients (aged 18-79 years) with clinical systolic BP ≥ 140 mm Hg (135 mm Hg in diabetics) and Home BP Monitoring (HBPM) systolic BP average ≥ 130 mm Hg on treatment for at least 3 months with maximum tolerated doses of A+C+D are randomised to four consecutive randomly allocated 12-week treatment cycles with an α-blocker, β-blocker, spironolactone and placebo. The hierarchical coprimary end point is the difference in HBPM average systolic BP between (in order) spironolactone and placebo, spironolactone and the average of the other two active drugs, spironolactone and each of the other two drugs. A key secondary outcome is to determine whether plasma renin predicts the BP response to the different drugs. A sample size of 346 (allowing 15% dropouts) will confer 90% power to detect a 3 mm Hg HBPM average systolic BP difference between any two drugs. The study can also detect a 6 mm Hg difference in HBPM average systolic BP between each patient's best and second-best drug predicted by tertile of plasma renin. ETHICS AND DISSEMINATION: The study was initiated in May 2009 and results are expected in 2015. These will provide RCT evidence to support future guideline recommendations for optimal drug treatment of resistant hypertension. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02369081, EUDract number: 2008-007149-30.The study is funded by a special project grant from the British Heart Foundation (number SP/08/002). Further funding is provided by the National Institute for Health Research (NIHR) Comprehensive Local Research Networks. BW is supported by the NIHR UCL/UCL Hospitals Biomedical Research Centre

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3):protocol for a randomised double-blind trial in patients with essential hypertension

INTRODUCTION: Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K(+)-depletion. We hypothesised that a K(+)-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K(+)-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide.METHODS AND ANALYSIS: This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25-50 mg, amiloride 10-20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18-79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate &lt;45 mL/min, abnormal plasma K(+), clinic SBP &gt;200 mm Hg or DBP &gt;120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators.ETHICS AND DISSEMINATION: PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal.TRIAL REGISTRATION NUMBERS: Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973.</p

Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial.

This is the final version of the article. It first appeared from BMJ via http://dx.doi.org/10.1136/bmjopen-2015-007645INTRODUCTION: Previous studies have suggested that more intensive initial therapy for hypertension results in better long-term blood pressure (BP) control. We test this hypothesis comparing initial monotherapy with dual therapy in the management of essential hypertension. METHODS AND ANALYSIS: The study is a prospective, multicentre, double-blind, active-controlled trial in patients with essential hypertension. Around 50% of patients studied will be newly diagnosed and the others will be known hypertensives who previously received only monotherapy. The trial is divided into three phases as follows: Phase 1 (Week 0-Week 16): Randomised, parallel-group, masked assignation to either combination or monotherapy. Phase 2 (Week 17-Week 32): Open-label combination therapy. Phase 3 (Week 33-Week 52): Open-label combination therapy plus open-label add-on (if BP is above 140/90 mm Hg). Hierarchical primary end points are: a comparison of home BP (home systolic blood pressure (HSBP)) averaged over the duration of phase 1 and 2 in the combination versus monotherapy arms. If combination is superior in this analysis, then the averaged mean HSBP between initial monotherapy and initial combination therapy at the end of phase 2 will be compared. Secondary end points include: BP control at 1 year; the role of age, baseline renin, sodium status, plasma volume, haemodynamic compensation and peripheral resistance on BP control; validation of the National Institute for Clinical Excellence/British Hypertension Society joint guideline algorithm; safety and tolerability of combination therapy; and the impact of combination versus monotherapy on left ventricular mass and aortic pulse wave velocity. A sample size of 536 (268 in each group) will have 90% power to detect a difference in means of 4 mm Hg. ETHICS AND DISSEMINATION: PATHWAY 1 was approved by UK ethics (REC Reference 09/H0308/132). Trial results will be published and all participating subjects will be informed of the results. TRIAL REGISTRATION NUMBER: UKCRN 4499 and EudraCT number 2008-007749-29 registered 27/08/2009.Funding statement The study is funded by a special project grant from the British Heart Foundation (number SP/08/002). Further funding is provided by Comprehensive Local Research Networks. The losartan and losartan-HCTZ were a generous gift from Dr Paul Robinson, Merck Sharpe Dohme, UK. Acknowledgements BW, PS, MC and MJB are NIHR Senior Investigators

Power-law singularities in string theory and M-theory

We extend the definition of the Szekeres-Iyer power-law singularities to supergravity, string and M-theory backgrounds, and find that are characterized by Kasner type exponents. The near singularity geometries of brane and some intersecting brane backgrounds are investigated and the exponents are computed. The Penrose limits of some of these power-law singularities have profiles $A\sim {\rm u}^{-\gamma}$ for $\gamma\geq 2$. We find the range of the exponents for which $\gamma=2$ and the frequency squares are bounded by 1/4. We propose some qualitative tests for deciding whether a null or timelike spacetime singularity can be resolved within string theory and M-theory based on the near singularity geometry and its Penrose limits.Comment: 32 page