Explore the vast range of titles available.

Objectives This retrospective study aimed to evaluate the effect of titration-guided focal selective retina therapy (SRT) for chronic central serous chorioretinopathy (cCSCR) and determine the need and effectiveness of re-treatment. Methods SRT was performed in 60 eyes of 57 patients with cCSCR, targeting focal leakage points (FLP) using a Nd:YLF-Laser at 527 nm (R:GEN®, Lutronic, South Korea) titration-guided at 80% threshold, with 140 ms irradiation time, 100 Hz frequency, 1.7 µs pulse duration, 200 µm spot size. Best documented visual acuity (BDVA), peak height of subretinal fluid (SRF), height of SRF at the fovea, central retinal thickness (cRT) and total macular retinal volume (tRV) were measured. Results A significant improvement in BDVA was observed up to 1 year compared to baseline ( p  < 0.02). A limited analysis due to the small sample size showed no significant difference between the BDVA at baseline and 2-year ( n  = 15) and 3-year ( n  = 10) follow-ups. A significant decrease in the height of the SRF at the highest point and fovea and total retinal volume up to the 3-year follow-up was observed compared to the baseline ( p  < 0.03). Thirty (50%) eyes of 30 patients required re-treatment, on average 9.2 ± 9.6 months after the initial SRT. This study found no predictors for the need of re-treatment. Conclusions The study concludes that SRT is safe and shows anatomical and functional benefits for treating cCSCR. We recommend performing regular check-ups every three months and following a zero-fluid tolerance policy for re-treatment. Trial registration German Clinical Trials Register ID: DRKS00031038, registration date: 2023-01-16

PurposeCentral serous chorioretinopathy (CSC) is a disease presenting with detachment of the neurosensory retina and characteristic focal leakage on fluorescein angiography. The spontaneous remission rate is 84% within 6 months. In this study, the efficacy of selective retina therapy (SRT) was examined in patients with therapy refractory persistent acute CSC defined by symptoms for at least 6 months and persistent subretinal fluid (SRF) despite eplerenone therapy.Material and methodsThis is a prospective, monocentric observational study in 17 eyes (16 patients, mean age 42 years, 2 female). SRT was performed with the approved R:GEN laser (Lutronic, South Korea), a micropulsed 527-nm Nd:YLF laser device, with a train of 30 pulses of 1.7 μs at 100-Hz repetition rate at the point of focal leakage determined by fluorescein angiography (FA) at baseline (BSL). Visits on BSL, week 4 (wk4), and week 12 (wk12) included best corrected visual acuity (BCVA, logMar), central retinal thickness (CRT) on spectral domain optical coherence tomography (SD-OCT), and FA. Statistical analysis was performed by pair-by-pair comparisons of multiple observations in each case with Bonferroni correction for multiple testing. (IBM SPSS Statistics 25®).ResultsMean CRT at BSL was 387.69 ± 110.4 μm. CRT significantly decreased by 106.31 μm in wk4 (95%-KI: 21.42–191.2; p = 0.01), by 133.63 μm in wk12 (95%-KI: 50.22–217.03; p = 0.001) and by 133.81 μm (95%-KI: 48.88–218.75; p = 0.001) compared to BSL. Treatment success defined as complete resolution of SRF occurred at wk4 in 7/17 eyes (35.3%) and at wk12 in 10/17 eyes (58.8%). Re-SRT was performed in 7/17 eyes (41.2%) after an average of 107.14 ± 96.59 days. Treatment success after Re-SRT was observed in 4/6 eyes (66.6%, 12 weeks after Re-SRT). Mean BCVA did not change significantly from BSL to any later timepoint after adjusting for multiple testing. Notably, eyes with treatment success showed better BCVA at all timepoints and gained more letters compared to failures.ConclusionSingle or repetitive SRT may be an effective and safe treatment in 2 of 3 patients suffering from acute persistent CSC after 6 months of symptoms or more. We observed complete resolution of SRF in around 60% of eyes 12 weeks after first SRT treatment and also 12 weeks after Re-SRT treatment in eyes with persistent or recurrent SRF. Results on the long-term course after SRT are still pending.

During its two-year prime mission, the Transiting Exoplanet Survey Satellite (TESS) will perform a time-series photometric survey covering over 80% of the sky. This survey comprises observations of 26 24° × 96° sectors that are each monitored continuously for approximately 27 days. The main goal of TESS is to find transiting planets around 200,000 pre-selected stars for which fixed aperture photometry is recorded every two minutes. However, TESS is also recording and delivering full-frame images (FFIs) of each detector at a 30-minutes cadence. We have created an open-source tool, eleanor, to produce light curves for objects in the TESS FFIs. Here, we describe the methods used in eleanor to produce light curves that are optimized for planet searches. The tool performs background subtraction; aperture and point-spread function photometry; decorrelation of instrument systematics; and cotrending using principal component analysis. We recover known transiting exoplanets in the FFIs to validate the pipeline and perform a limited search for new planet candidates in Sector 1. Our tests indicate that eleanor produces light curves with significantly less scatter than other tools that have been used in the literature. Cadence-stacked images, and raw and detrended eleanor light curves for each analyzed star will be hosted on Mikulski Archive for Space Telescopes, with planet candidates on ExoFOP-TESS as Community TESS Objects of Interest. This work confirms the promise that the TESS FFIs will enable the detection of thousands of new exoplanets and a broad range of time domain astrophysics.

Acute myeloid leukemia (AML) is a rapidly progressive malignancy without effective therapies for refractory disease. So far, chimeric antigen receptor (CAR) T cell therapy in AML has not recapitulated the efficacy seen in B cell malignancies. Here we report a pilot study of autologous anti-CD123 CAR T cells in 12 adults with relapsed or refractory AML. CAR T cells targeting CD123 + cells were successfully manufactured in 90.4% of runs. Cytokine release syndrome was observed in 10 of 12 infused individuals (83.3%, 90% confidence interval 0.5–0.97). Three individuals achieved clinical response (25%, 90% confidence interval 0.07–0.53). We found that myeloid-supporting cytokines are secreted during cell therapy and support AML blast survival via kinase signaling, leading to CAR T cell exhaustion. The prosurvival effect of therapy-induced cytokines presents a unique resistance mechanism in AML that is distinct from any observed in B cell malignancies. Our findings suggest that autologous CART manufacturing is feasible in AML, but treatment is associated with high rates of cytokine release syndrome and relatively poor clinical efficacy. Combining CAR T cell therapies with cytokine signaling inhibitors could enhance immunotherapy efficacy in AML and achieve improved outcomes (ClinicalTrials.gov identifier: NCT03766126 ). In a phase 1 trial followed by translational analyses, patients with acute myeloid leukemia (AML) treated with chimeric antigen receptor (CAR) T cell therapy targeting CD123 experienced high levels of cytokine release syndrome and short-lived clinical responses, probably due to CAR T cell-derived cytokines increasing the viability of AML blasts and antigen persistence.

Work-related musculoskeletal disorders (WMSDs) are prevalent in occupations characterised by high repetition and high force demands. Both factors not only evoke inflammatory and degenerative processes in affected musculoskeletal tissue, but also systemic responses identified by biomarkers in blood serum. Clarifying methodological aspects of biomarkers may provide insights into their predictive role in the pathway of developing WMSDs. This study will primarily assess reliability of systemic inflammatory biomarkers (CRP, TNF-α, IL-6, IL-1β) and immune cell reactivity by repeated measures in workers with constant workloads over time. This observational cross-sectional study will include two groups of workers: exposed group including workers exposed to higher upper-extremity physical workloads, especially affecting the elbow/forearm/hand-area; unexposed group, including office workers exposed to lower upper-extremity physical workloads. Recruited persons are screened against eligibility criteria followed by a medical anamnesis and blood analysis. Enrolled participants undergo nine repeated measurements once every two weeks, taking blood among others. Blood analyses will determine values of systemic inflammatory biomarkers and reactivity of immune cells. The absolute test-retest reliability of biomarkers and immune cell reactivity over time is assessed by the intra-class correlation coefficient applying two-way mixed-effects models. The relative test-retest reliability is assessed by the standard error of measurement. Knowledge of and models currently describing the pathological role of systemic inflammatory biomarkers are based on highly-controlled laboratory rat experiments. This study has the strength of assessing a human population under real-life conditions. The major challenge is in participant recruitment given the intensive and complex study design. The results of this study could provide fundamentals for initiating a cohort study and be used for developing work-related stress-recovery concepts for occupations with different physical demands to identify workers who may be at risk for developing WMSDs. German Clinical Trials Register (DRKS00031872, 25 May 2023).

Lake surfaces are warming worldwide, raising concerns about lake organism responses to thermal habitat changes. Species may cope with temperature increases by shifting their seasonality or their depth to track suitable thermal habitats, but these responses may be constrained by ecological interactions, life histories or limiting resources. Here we use 32 million temperature measurements from 139 lakes to quantify thermal habitat change (percentage of non-overlap) and assess how this change is exacerbated by potential habitat constraints. Long-term temperature change resulted in an average 6.2% non-overlap between thermal habitats in baseline (1978–1995) and recent (1996–2013) time periods, with non-overlap increasing to 19.4% on average when habitats were restricted by season and depth. Tropical lakes exhibited substantially higher thermal non-overlap compared with lakes at other latitudes. Lakes with high thermal habitat change coincided with those having numerous endemic species, suggesting that conservation actions should consider thermal habitat change to preserve lake biodiversity.Using measurements from 139 global lakes, the authors demonstrate how long-term thermal habitat change in lakes is exacerbated by species’ seasonal and depth-related constraints. They further reveal higher change in tropical lakes, and those with high biodiversity and endemism.

ObjectiveInvestigate the effect of passive, active or no intra-operative work breaks on static, median and peak muscular activity, muscular fatigue, upper body postures, heart rate, and heart rate variability. BackgroundAlthough laparoscopic surgery is preferred over open surgery for the benefit of the patient, it puts the surgeons at higher risk for developing musculoskeletal disorders especially due to the less dynamic and awkward working posture. The organizational intervention intraoperative work break is a workplace strategy that has previously demonstrated positive effects in small-scale intervention studies. MethodsTwenty-one surgeons were exposed to three 90-min conditions: no breaks, 2.5-min passive (standing rest) or active (targeted stretching and mobilization exercises) breaks after 30-min work blocks. Muscular activity and fatigue of back, shoulder and forearm muscles were assessed by surface electromyography; upper body posture, i.e., spinal curvature, by inclination sensors; and heart rate and variability (HRV) by electrocardiography. Generalized estimating equations were used for statistical analyses. This study (NCT03715816) was conducted from March 2019 to October 2020.ResultsThe HRV-metric SDNN tended to be higher, but not statistically significantly, in the intervention conditions compared to the control condition. No statistically significant effects of both interventions were detected for muscular activity, joint angles or heart rate.ConclusionIntraoperative work breaks, whether passive or active, may counteract shoulder muscular fatigue and increase heart rate variability. This tendency may play a role in a reduced risk for developing work-related musculoskeletal disorders and acute physical stress responses.

Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

IntroductionLaparoscopy has partially replaced open surgery due to the lower infection rate for the patient and hence better and shorter recovery. However, the surgeon’s physical load is higher due to longer duration static and awkward body postures, increasing the risk for developing work-related musculoskeletal disorders. Interventions of an organisational nature are work breaks, being either passive or active. The primary objectives of this study are to determine whether passive and active work breaks lead to less discomfort than no work breaks and whether active work breaks lead to less discomfort than passive work breaks.Methods and analysisA controlled, randomised cross-over trial will be performed in the laboratory, of which its protocol is described here according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement. Recruitment of 21 laparoscopic surgeons started in April 2019 and the study is ongoing. The participating surgeons will perform three 1.5 hour experimental conditions, one without work breaks, one with 2.5 min passive work breaks including rest, and one with 2.5 min active work breaks including mobility and stretching exercises. The work breaks will be taken after 30 and 60 min of work. During the experiments, outcomes will be recorded. The primary outcome is rating of perceived discomfort measured on an 11-point numeric rating scale. The secondary outcomes are performance, muscle activity of selected muscles, upper body angles, heart rate, workload and subjective evaluation of both interventions. The collected data will be tested using a one-way or two-factorial repeated-measures analysis of variance.Ethics and disseminationEthical approval of the study protocol was received by the local medical ethical committee of the University of Tübingen in February 2019 (no 618/2018BO2). The results of this study will be presented at national and international conferences, submitted for publications in peer-reviewed journals and serve as the starting point for a feasibility study.Trial registration numberNCT03715816.

We describe a software package called VPLanet that simulates fundamental aspects of planetary system evolution over Gyr timescales, with a focus on investigating habitable worlds. In this initial release, eleven physics modules are included that model internal, atmospheric, rotational, orbital, stellar, and galactic processes. Many of these modules can be coupled to simultaneously simulate the evolution of terrestrial planets, gaseous planets, and stars. The code is validated by reproducing a selection of observations and past results. VPLanet is written in C and designed so that the user can choose the physics modules to apply to an individual object at runtime without recompiling, i.e., a single executable can simulate the diverse phenomena that are relevant to a wide range of planetary and stellar systems. This feature is enabled by matrices and vectors of function pointers that are dynamically allocated and populated based on user input. The speed and modularity of VPLanet enables large parameter sweeps and the versatility to add/remove physical phenomena to assess their importance. VPLanet is publicly available from a repository that contains extensive documentation, numerous examples, Python scripts for plotting and data management, and infrastructure for community input and future development.