Tracking the kinematics of caudal-oscillatory swimming : a comparison of two on-animal sensing methods

Funding: Marie Sklodowska Curie Career Integration Grant and by The Marine Alliance for Science and Technology for Scotland (MASTS).Studies of locomotion kinematics require high-resolution information about body movements and the specific acceleration (SA) that these generate. On-animal accelerometers measure both orientation and SA but an additional orientation sensor is needed to accurately separate these. Although gyroscopes can perform this function, their power consumption, drift and complex data processing make them unattractive for biologging. Lower power magnetometers can also be used with some limitations. Here, we present an integrated and simplified method for estimating body rotations and SA applicable to both gyroscopes and magnetometers, enabling a direct comparison of these two sensors. We use a tag with both sensors to demonstrate how caudal-oscillation rate and SA are adjusted by a diving whale in response to rapidly changing buoyancy forces as the lungs compress while descending. Both sensors gave similar estimates of the dynamic forces demonstrating that magnetometers may offer a simpler low-power alternative for miniature tags in some applications.PostprintPeer reviewe

Whispering gallery quantum well exciton polaritons in an Indium Gallium Arsenide microdisk cavity

Despite appealing high-symmetry properties that enable high quality factor and strong confinement, whispering gallery modes of spherical and circular resonators have been absent from the field of quantum-well exciton polaritons. Here we observe whispering gallery exciton polaritons in a Gallium Arsenide microdisk cavity filled with Indium Gallium Arsenide quantum wells, the testbed materials of polaritonics. Strong coupling is evidenced in photoluminescence and resonant spectroscopy, accessed through concomitant confocal microscopy and near-field optical techniques. Excitonic and optical resonances are tuned by varying temperature and disk radius, revealing Rabi splittings between 5 and 10 meV. A dedicated analytical quantum model for such circular polaritons is developed, which reproduces the measured values. At high power, lasing is observed and accompanied by a blueshift of the emission that points to the regime of polariton lasing

Gait switches in deep-diving beaked whales : biomechanical strategies for long-duration dives

Work in the Canary Islands was funded by the Office of Naval Research and the National Oceanographic Partnership Program (NOPP), by a consortium consisting of the Canary Islands Government, the Spanish Ministry of Environment and the Spanish Ministry of Defense and by the European environmental funding LIFE-INDEMARES program for the inventory and designation of the Natura 2000 network in marine areas of the Spanish territory, headed by Fundacion Biodiversidad, with additional support from the Cabildo Insular of El Hierro. Fieldwork in the Ligurian Sea was funded by NOPP. Research in the Gully was funded by the Strategic Environmental Research and Development Program (SERDP) programs RC-2113 and RC-2337. L.M.M.L. was funded by a ‘la Caixa’ Fellowship within the 2010 UK Framework Programme. N.A.d.S. was funded for this study by ONR and by the EU FP7 Marie Curie project SOUNDMAR. M.J. was funded by a Marie Curie Career Integration Grant, and from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) and their support is gratefully acknowledged. MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions.Diving animals modulate their swimming gaits to promote locomotor efficiency and so enable longer, more productive dives. Beaked whales perform extremely long and deep foraging dives that probably exceed aerobic capacities for some species. Here, we use biomechanical data from suction-cup tags attached to three species of beaked whales (Mesoplodon densirostris, N = 10; Ziphius cavirostris, N = 9; and Hyperoodon ampullatus, N = 2) to characterize their swimming gaits. In addition to continuous stroking and stroke and-glide gaits described for other diving mammals, all whales produced occasional fluke-strokes with distinctly larger dorsoventral acceleration, which we termed 'type-B' strokes. These high-power strokes occurred almost exclusively during deep dive ascents as part of a novel mixed gait. To quantify body rotations and specific acceleration generated during strokes we adapted a kinematic method combining data from two sensors in the tag. Body rotations estimated with high-rate magnetometer data were subtracted from accelerometer data to estimate the resulting surge and heave accelerations. Using this method, we show that stroke duration, rotation angle and acceleration were bi-modal for these species, with B-strokes having 76% of the duration, 52% larger body rotation and four times more surge than normal strokes. The additional acceleration of B-strokes did not lead to faster ascents, but rather enabled brief glides, which may improve the overall efficiency of this gait. Their occurrence towards the end of long dives leads us to propose that B-strokes may recruit fast-twitch fibres that comprise similar to 80% of swimming muscles in Blainville's beaked whales, thus prolonging foraging time at depth.PostprintPeer reviewe

Guidance of adjuvant instillation in intermediate-risk non-muscle invasive bladder cancer by drug screens in patient derived organoids: a single center, open-label, phase II trial.

BACKGROUND In intermediate-risk non-muscle invasive bladder cancer (NMIBC) clinical guidelines suggest an adjuvant instillation with a chemotherapeutic agent. However, the agent and regimen are not clearly defined. Worldwide, less than 15% of patients receive this adjuvant chemotherapeutic instillation. We recently developed a pipeline for the generation of patient derived organoids (PDO) in NMIBC. In this phase II trial, we aim to use our in vitro pipeline to select the most effective drug for chemotherapeutic instillation in NMIBC patients. METHODS Patients with first diagnosis of intermediate-risk NMIBC that are directed to transurethral resection of bladder tumor (TURBT) are enrolled. During TURBT, tumor is sampled, and specimens are directed to generate PDO. Once the PDO are formed, drug screens on them for Epirubicin, Mitomycin C, Gemcitabine and Docetaxel are performed. The drug with the highest antitumor activity in vitro will then be selected for 6 adjuvant intravesical instillations once weekly. Thereafter, patients are followed according to clinical guidelines by cystoscopy. DISCUSSION The aim of this trial is to use drug screens in PDO to precise treatment selection for adjuvant instillation therapies in patients with intermediate-risk NMIBC. The ultimate goal of this trial is to reduce the risk of cancer recurrence. In the future, we aim to conduct clinical multicenter trials with an increased sample size, a broader panel of compounds and a focus on the reduction of cancer recurrence by precision delivery of care. Trial registration NCT05024734

No Untoward Effect of Long-Term Ketoconazole Administration on Electrocardiographic QT Interval in Patients with Cushing's Disease.

Ketoconazole is listed among drugs that prolong QT interval and may increase the risk of torsade de pointes, a severe ventricular arrhythmia. This compound has recently been approved for treatment of Cushing's syndrome, a severe endocrine disorder. These patients harbour several risk factors for prolonged QT interval, for example hypokalaemia and left ventricular hypertrophy, but no study has evaluated whether administration of ketoconazole affects their QT interval. The aim of this study was to assess the QT interval in patients with Cushing's disease during long-term administration of ketoconazole. Electrocardiograms from 15 patients with Cushing's disease (12 women, 3 men, age: 37.8 ± 2.66 years) on ketoconazole treatment (100 mg-800 mg qd) for 1 month to 12 years were reviewed retrospectively. QT interval was measured and corrected for heart rate (QTc). Measurements before and during ketoconazole treatment were compared and any abnormal QTc value recorded. Concurrent medical therapies were also documented. On average, QTc was superimposable before and during ketoconazole treatment (393.2 ± 7.17 versus 403.3 ± 6.05 msec. in women; 424.3 ± 23.54 versus 398.0 ± 14.93 msec. in men, N.S.). QTc normalized on ketoconazole in one man with prolonged QTc prior to treatment; no abnormal QTc was observed in any other patient during the entire observation period, even during concurrent treatment with other QT-prolonging drugs. In conclusion, long-term ketoconazole administration does not appear to be associated with significant prolongation of QT interval in patients with Cushing's disease. ECG monitoring can follow recommendations drawn for other low-risk QT-prolonging drugs with attention to specific risk factors, for example hypokalaemia and drug interactions

The Spinal Transcriptome after Cortical Stroke: In Search of Molecular Factors Regulating Spontaneous Recovery in the Spinal Cord

In response to cortical stroke and unilateral corticospinal tract degeneration, compensatory sprouting of spared corticospinal fibers is associated with recovery of skilled movement in rodents. To date, little is known about the molecular mechanisms orchestrating this spontaneous rewiring. In this study, we provide insights into the molecular changes in the spinal cord tissue after large ischemic cortical injury in adult female mice, with a focus on factors that might influence the reinnervation process by contralesional corticospinal neurons. We mapped the area of cervical gray matter reinnervation by sprouting contralesional corticospinal axons after unilateral photothrombotic stroke of the motor cortex in mice using anterograde tracing. The mRNA profile of this reinnervation area was analyzed using whole-genome sequencing to identify differentially expressed genes at selected time points during the recovery process. Bioinformatic analysis revealed two phases of processes: early after stroke (4-7 d post-injury), the spinal transcriptome is characterized by inflammatory processes, including phagocytic processes as well as complement cascade activation. Microglia are specifically activated in the denervated corticospinal projection fields in this early phase. In a later phase (28-42 d post-injury), biological processes include tissue repair pathways with upregulated genes related to neurite outgrowth. Thus, the stroke-denervated spinal gray matter, in particular its intermediate laminae, represents a growth-promoting environment for sprouting corticospinal fibers originating from the contralesional motor cortex. This dataset provides a solid starting point for future studies addressing key elements of the post-stroke recovery process, with the goal to improve neuroregenerative treatment options for stroke patients. SIGNIFICANCE STATEMENT We show that the molecular changes in the spinal cord target tissue of the stroke-affected corticospinal tract are mainly defined by two phases: an early inflammatory phase during which microglia are specifically activated in the target area of reinnervating corticospinal motor neurons; and a late phase during which growth-promoting factors are upregulated which can influence the sprouting response, arborization, and synapse formation. By defining for the first time the endogenous molecular machinery in the stroke-denervated cervical spinal gray matter with a focus on promotors of axon growth through the growth-inhibitory adult CNS, this study will serve as a basis to address novel neuroregenerative treatment options for chronic stroke patients

Handbook of Territorial and Local Development Strategies

All places are important to the future wellbeing of Europe. The European Union (EU) is committed to ensuring that the development potential of places is uncovered and valorised. Integrated territorial and local develop- ment strategies promoted by EU cohesion policy are relevant tools to sustain this process. The ‘Handbook of Territorial and Local Development Strategies’ provides valuable knowledge on how to design and implement integrated strategies in areas other than urban areas. It aims to serve managing authorities of operational programmes, local strategy owners as well as other stakeholders involved in the process. The Handbook is a joint initiative by the European Commission’s Directorates-General for Regional and Urban Policy (DG REGIO) and the Joint Research Centre (JRC), and it benefits from the active contribution of policy-makers, practitioners and scholars

β3-Adrenoceptor-mediated relaxation of rat and human urinary bladder:roles of BKCa channels and Rho kinase

Previous studies suggest that the large-conductance Ca2+-activated K+ (BKCa) channel and Rho-kinase play major roles in the control of urinary bladder tone. Here, we investigated their involvement in beta-adrenoceptor (AR)-mediated relaxation of rat and human bladder. Concentration-response curves of isoprenaline and mirabegron-induced bladder relaxation were generated against passive tension and KCl- and carbachol-induced tone, in the absence or presence of the BKCa channel inhibitor iberiotoxin (100 nM) or the Rho-kinase inhibitor Y27,632 (1 mu M). Myosin light chain (MLC) phosphorylation was studied by Western blot. In rat, iberiotoxin only slightly altered isoprenaline- and mirabegron-induced relaxation against KCl-induced tone but attenuated relaxation by both agonists against carbachol-induced tone. Y27,632 enhanced isoprenaline- or mirabegron-induced relaxation only against carbachol-induced tone. In humans, iberiotoxin slightly enhanced relaxation by both agonists against carbachol-induced pre-contraction. Y27,632 did not change isoprenaline-induced relaxation but enhanced that by mirabegron. Under passive tension, MLC phosphorylation was markedly reduced by both beta-AR agonists, an effect insensitive to Y27,632. In the presence of carbachol, both beta-AR agonists increased MLC phosphorylation, an effect reduced by Y27,632 only in the presence of 1 mu M carbachol. These results indicate that the extent of BKCa channel and Rho-kinase involvement in relaxation induced by beta-AR agonists depends on pre contractile stimulus and species

Exploring the relationship between loneliness and social cognition in older age

Understanding others is a key component of successful social interactions, and declines in social abilities during later life can lead to social isolation and loneliness. We investigated the relationship between different sub-components of social cognition and loneliness in a large sample of older adults. We tested perspective-taking and mentalizing skills, alongside self-reported loneliness and social functioning. Results revealed that both loneliness and age correlated significantly with older adults’ ability to resist egocentric interference when taking others’ perspectives. However, mediation models showed that the effect of loneliness on egocentric tendencies was eliminated when age was accounted for. Therefore, loneliness relates to egocentrism only because egocentric tendencies increase with age, and people experience increasing levels of loneliness and feelings of social isolation with increasing age. Mentalizing and interference from others’ perspectives were not influenced by loneliness or age

A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility

Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio. In this subset of patients, and particularly in those with hypogonadism, elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic-pituitary-testicular axis by suppressing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production and impaired spermatogenesis. Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment. We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males. Overall, eight original articles were included and critically evaluated. Either steroidal (Testolactone) or nonsteroidal (Anastrozole and Letrozole) aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile. While the evidence is promising, future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications