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Background Visualizing the specific regions where atrial fibrillation (AF) is maintained is crucial for effective treatment, but it remains challenging in clinical practice. We aimed to address this challenge by developing a mapping approach focused on the cycle length (CL) and its gradient (CL‐gradient). Methods In 105 patients undergoing initial ablation for persistent AF, pre‐ablation CARTOFINDER data were utilized to create maps based on three indicators: (1) CL, the atrial frequency during AF calculated using CARTOFINDER; (2) Short CL, encompassing CLs within 5 ms of the minimum CL; and (3) CL‐gradient, the CL range within a 6 mm radius. We evaluated the association between the AF termination through ablation and the measured values and patterns in each map. Results AF termination occurred in 17 patients. The AF termination group exhibited the significant large maximum CL‐gradient (48.8 ms [interquartile range, 38.6–66.3], p <.001) and the short distance between the minimum CL site and the maximum CL‐gradient site (15.8 mm, [interquartile range, 6.0–23.2], p =.029). Of the 17 AF termination cases, 13 exhibited a CL distribution pattern characterized by a steep CL‐gradient near the minimum CL site (SG‐MCL), defined as the distance of less than 23.2 mm and the maximum CL‐gradient greater than 33.1 ms. In these AF termination cases, SG‐MCL was also correlated with the ablation area. Conclusions The minimum CL area accompanied by significant CL gradients in the immediate vicinity may play a crucial role in sustaining AF. Identifying regions that maintain atrial fibrillation (AF) is essential but challenging. This study proposes a promising method for mapping AF in clinical cases by creating maps of the cycle length (CL) and CL‐gradients using CARTOFINDER data. Assuming that the area where AF terminates during ablation represents the AF driver region, we examined the features of these maps. The ablation areas leading to AF termination exhibited the minimum CL, accompanied by steep CL‐gradients in the immediate vicinity.

1. Mammalian sleep is composed of two distinct states - rapid-eye-movement (REM) and non-REM (NREM) sleep - that alternate in cycles over a sleep bout. The duration of these cycles varies extensively across mammalian species. Because the end of a sleep cycle is often followed by brief arousals to waking, a shorter sleep cycle has been proposed to function as an anti-predator strategy. Similarly, higher predation risk could explain why many species exhibit a polyphasic sleep pattern (division of sleep into several bouts per day), as having multiple sleep bouts avoids long periods of unconsciousness, potentially reducing vulnerability. 2. Using phylogenetic comparative methods, we tested these predictions in mammals, and also investigated the relationships among sleep phasing, sleep-cycle length, sleep durations and body mass. 3. Neither sleep-cycle length nor phasing of sleep was significantly associated with three different measures of predation risk, undermining the idea that they represent anti-predator adaptations. 4. Polyphasic sleep was associated with small body size, shorter sleep cycles and longer sleep durations. The correlation with size may reflect energetic constraints: small animals need to feed more frequently, preventing them from consolidating sleep into a single bout. The reduced daily sleep quotas in monophasic species suggests that the consolidation of sleep into one bout per day may deliver the benefits of sleep more efficiently and, since early mammals were small-bodied and polyphasic, a more efficient monophasic sleep pattern could be a hitherto unrecognized advantage of larger size.

Background Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects. Objective Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS. Methods The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs). Results Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD  =  -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD  =  -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85). Conclusion Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin. Trial registration PROSPERO registration number: CRD42021283275.

Abstract Context While age-related changes in menstrual cycle length are well known, it is unclear whether anti-Müllerian (AMH) or other ovarian reserve biomarkers have a direct association with cycle length. Objective To determine the association between biomarkers of ovarian reserve and menstrual cycle length. Methods Secondary analysis using data from time to conceive (TTC), a prospective time to pregnancy cohort study. The age-independent association between cycle length and biomarkers of ovarian reserve was analyzed using linear mixed and marginal models. Study participants were TTC-enrolled women aged 30-44 years with no history of infertility who were attempting to conceive for <3 months were enrolled. Serum AMH, follicle-stimulating hormone, and inhibin B levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months. The primary outcome was menstrual cycle length; follicular and luteal phase lengths were secondary outcomes. Results Multivariable analysis included 1880 cycles from 632 women. Compared with AMH levels of 1.6 to 3.4 ng/mL, women with AMH <1.6 ng/mL had cycles and follicular phases that were 0.98 (95% CI –1.46, –0.50) and 1.58 days shorter (95% CI –2.53, –0.63), respectively, while women with AMH >8 ng/mL had cycles that were 2.15 days longer (95% CI 1.46, 2.83), follicular phases that were 2 days longer (95% CI 0.77, 3.24), and luteal phases that were 1.80 days longer (95% CI 0.71, 2.88). Conclusion Increasing AMH levels are associated with longer menstrual cycles due to both a lengthening of the follicular and the luteal phase independent of age.

This research enhances and evaluates the performance of a Decentralized Nash Bargaining (DNB) adaptive traffic signal controller that operates a flexible National Electrical Manufacturers Association (NEMA) phasing and timing scheme responding dynamically to fluctuating traffic demands. The DNB controller is enhanced to (1) use traffic density estimates instead of queues to optimize signal timings; (2) to consider the eight-phase two-ring NEMA controller configuration within the game-theoretic approach; and (3) to consider dynamically adaptable control time steps. The enhanced DNB controller is benchmarked against (1) a fixed-time traffic signal control using the state-of-practice Webster’s method and an emerging Laguna-Du-Rakha (LDR) method for computing the optimum cycle length; (2) a state-of-the-practice actuated traffic signal control; and (3) a state-of-the-art reinforcement learning (RL) traffic signal controller presented in the literature. The controller is tested on two isolated signalized intersections, demonstrating enhanced overall intersection performance compared to the baseline pretimed and actuated controllers at various demand levels, and offers better performance than a previously developed RL controller. Specifically, the DNB controller results in a decrease in the average vehicle delay and queue size by up to 54% and 63%, respectively, compared to Webster’s state-of-the-practice pretimed control. Unlike the RL controller, the DNB controller requires no pre-training while adapting to fluctuating traffic conditions, thereby providing a flexible framework for reducing traffic congestion at signalized intersections. As such, this research contributes to the development of smarter and more responsive urban traffic control systems.

STUDY QUESTIONWhat variations underlie the menstrual cycle length and ovulation day of women trying to conceive?SUMMARY ANSWERBig data from a connected ovulation test revealed the extent of variation in menstrual cycle length and ovulation day in women trying to conceive.WHAT IS KNOWN ALREADYTiming intercourse to coincide with the fertile period of a woman maximises the chances of conception. The day of ovulation varies on an inter- and intra-individual level.STUDY DESIGN, SIZE, DURATIONA total of 32 595 women who had purchased a connected ovulation test system contributed 75 981 cycles for analysis. Day of ovulation was determined from the fertility test results. The connected home ovulation test system enables users to identify their fertile phase. The app benefits users by enabling them to understand their personal fertility information. During each menstrual cycle, users input their perceived cycle length into an accessory application, and data on hormone levels from the tests are uploaded to the application and stored in an anonymised cloud database. This study compared users’ perceived cycle characteristics with actual cycle characteristics. The perceived and actual cycle length information was analysed to provide population ranges.PARTICIPANTS/MATERIALS, SETTING, METHODSThis study analysed data from the at-home use of a commercially available connected home ovulation test by women across the USA and UK.MAIN RESULTS AND THE ROLE OF CHANCEOverall, 25.3% of users selected a 28-day cycle as their perceived cycle length; however, only 12.4% of users actually had a 28-day cycle. Most women (87%) had actual menstrual cycle lengths between 23 and 35 days, with a normal distribution centred on day 28, and over half of the users (52%) had cycles that varied by 5 days or more. There was a 10-day spread of observed ovulation days for a 28-day cycle, with the most common day of ovulation being Day 15. Similar variation was observed for all cycle lengths examined. For users who conducted a test on every day requested by the app, a luteinising hormone (LH) surge was detected in 97.9% of cycles.LIMITATIONS, REASONS FOR CAUTIONData were from a self-selected population of women who were prepared to purchase a commercially available product to aid conception and so may not fully represent the wider population. No corresponding demographic data were collected with the cycle information.WIDER IMPLICATIONS OF THE FINDINGSUsing big data has provided more personalised insights into women’s fertility; this could enable women trying to conceive to better time intercourse, increasing the likelihood of conception.STUDY FUNDING/COMPETING INTERESTSThe study was funded by SPD Development Company Ltd (Bedford, UK), a fully owned subsidiary of SPD Swiss Precision Diagnostics GmbH (Geneva, Switzerland). I.S., B.G. and S.J. are employees of the SPD Development Company Ltd.

The main objective of this study was to evaluate the effects of salt stress on the photosynthetic electron transport chain using two chickpea lines (Cicer arietinum L.) differing in their salt stress tolerance at the germination stage (AKN 87 and AKN 290). Two weeks after sowing, seedlings were exposed to salt stress for 2 weeks and irrigated with 200 ml of 200 mM NaCl every 2 days. The polyphasic OJIP fluorescence transient and the 820-nm transmission kinetics (photosystem I) were used to evaluate the effects of salt stress on the functionality of the photosynthetic electron transport chain. It was observed that a signature for salt stress was a combination of a higher J step (VJ), a smaller IP amplitude, and little or no effect on the primary quantum yield of PSII (φPo). We observed for AKN 290 a shorter leaf life cycle, which may represent a mechanism to cope with salt stress. For severely salt-stressed leaves, an inhibition of electron flow between the PQ pool and P700 was found. The data also suggest that the properties of electron flow beyond PSI are affected by salt stress.

One of the main ionization sources of the F2 region of the Earth’s ionosphere is the solar EUV irradiance accounting for ~ 90% of its variability during quiet time. Consequently, prior to long-term trend estimations solar activity must be filtered out. The last two solar activity cycles present low activity levels, and particularly solar cycle 24 is the lowest in the last ten solar cycles. The effect of the inclusion of this last solar cycle on foF2 trend estimation is analyzed for two mid-latitude ionospheric stations: Kokubunji (35.7°N, 139.5°E) and Wakkanai (45.4°N, 141.7°E). Filtering is done considering the residuals of different regressions between foF2 and Rz and also between foF2 and F10.7. In both cases, foF2 trends become less negative when solar cycle 24 is included in trend estimations since foF2 residuals systematically exceeds the values predicted by a linear, quadratic or cubic fit between foF2 and F10.7 or Rz from 2008 onwards. In addition, the Earth’s magnetic field secular variation at both stations would induce a positive foF2 trend during daytime that could counteract the greenhouse gases decreasing trend. It is interesting to think that including the latest solar cycles does not necessarily imply incorrect results in the statistical analysis of the data, but simply that solar activity is decreasing on average and also the trend.

PurposeThis study aimed to compare physiological factors and cycle characteristics during cross-country (XC) roller-skiing at matched inclines and speeds using the double-poling (DP) and diagonal-stride (DS) sub-techniques in junior female and male XC skiers.MethodsTwenty-three well-trained junior XC skiers (11 women, 12 men; age 18.2 ± 1.2 yr.) completed two treadmill roller-skiing tests in a randomized order using either DP or DS. The exercise protocols were identical and included a 5 min warm-up, 4 × 5 min submaximal stages, and an incremental test to exhaustion, all performed at a 5° incline.ResultsNo significant three-way interactions were observed between sex, submaximal exercise intensity, and sub-technique. For the pooled sample, higher values were observed for DP versus DS during submaximal exercise for the mean oxygen uptake kinetics response time (33%), energy cost (18%), heart rate (HR) (9%), blood lactate concentration (5.1 versus 2.1 mmol·L−1), rating of perceived exertion (12%), and cycle rate (25%), while cycle length was lower (19%) (all P < 0.001). During the time-to-exhaustion (TTE) test, peak oxygen uptake (V˙O2peak), peak HR, and peak oxygen pulse were 8%, 2%, and 6% lower, respectively, for DP than DS, with a 29% shorter TTE during DP (pooled data, all P < 0.001).ConclusionIn well-trained junior XC skiers, DP was found to exert a greater physiological load than DS during uphill XC roller-skiing at submaximal intensities. During the TTE test, both female and male athletes were able to ski for longer and reached markedly higher V˙O2peak values when using DS compared to DP.

The adult mammalian heart is non-regenerative because cardiomyocytes withdraw from the cell cycle shortly after birth. Embryonic mammalian hearts, in which cardiomyocytes are genetically ablated in a salt-and-pepper–like pattern, regenerate due to compensation by residual cardiomyocytes. To date, it remains unknown whether or how transmural ventricular defects at the looped heart stage regenerate after cryoinjury. We established a cryoablation model in stage 16 chick embryonic hearts. In hearts at 5 h post cryoinjury (hpc), cryoinjury-induced defects were approximately 200 µm in width in the primitive ventricle; thereafter, the defect was filled with mesenchymal cells accumulating between the epicardium and endocardium. The defect began to regress at 4 days post cryoinjury (dpc) and disappeared around 9 dpc. Immunohistochemistry showed that there were no isl1-positive cells in either the scar tissue or residual cardiomyocytes. BrdU incorporation into residual cardiomyocytes was transiently downregulated in association with upregulation of p27 (Kip1), suggesting that cell cycle arrest occurred at G1-to-S transition immediately after cryoinjury. Estimated cell cycle length was examined, and the results showed that the shortest cell cycle length was 18 h at stages 19–23; it increased with development due to elongation of the G2-M-G1 phase and 30 h at stages 27–29. The S phase length was constant at 6–8 h. The cell cycle length was elongated immediately after cryoinjury, and it reversed at 1–2 dpc. Cryoablated transmural defects in the early embryonic heart were restored by compensation by residual myocytes.