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BackgroundRepolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, is one of the cornerstones of cardiac electrophysiology as it provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., period-4, period-8,…) are expected but have very limited experimental evidence.MethodsWe studied explanted human hearts, obtained from the recipients of heart transplantation at the time of surgery, using optical mapping technique with transmembrane voltage-sensitive fluorescent dyes. The hearts were stimulated at an increasing rate until VF was induced. The signals recorded from the right ventricle endocardial surface just before the induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics.ResultsA prominent and statistically significant 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local analysis revealed the spatiotemporal distribution of higher-order periods. Period-4 was localized to temporally stable islands. Higher-order oscillations (period-5, 6, and 8) were transient and primarily occurred in arcs parallel to the activation isochrones.DiscussionWe present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts before VF induction. This result is consistent with the period-doubling route to chaos as a possible mechanism of VF initiation, which complements the concordant to discordant alternans mechanism. The presence of higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation.

As Chinese legal system follows a statutory tradition, the writing of Chinese judicial opinions is normally considered as an invariant sequential process of stating the law, presenting the fact, and finally providing the conclusion. The official ideology is further reinforced by the fact that Chinese judges need to follow various authoritative writing guidelines and templates prescribed by the official bodies of legal profession. This paper examines to what extent this ideology is a trustworthy description, and to what extent it is only an imagined myth related to the rhetorical practices of Chinese legal profession. Theoretical constructs employed in the study are genre, text type, and rhetorical modes, and analytical data include exemplar judicial opinions, intertextual legislative documents, and insiders’ accounts. According to the research findings, while the official ideology remains a strong shaping force in the composing of Chinese judicial opinions, Chinese judges do take compelling moves to add dialogic elements to the traditionally monologue-dominated discursive sphere of legal writing.

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Purpose: Ketogenic diets are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that ketogenic diets enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative stress.Experimental Design: Mice bearing NCI-H292 and A549 lung cancer xenografts were fed a ketogenic diet (KetoCal 4:1 fats: proteins+carbohydrates) and treated with either conventionally fractionated (1.8–2 Gy) or hypofractionated (6 Gy) radiation as well as conventionally fractionated radiation combined with carboplatin. Mice weights and tumor size were monitored. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)–modified proteins as a marker of oxidative stress as well as proliferating cell nuclear antigen (PCNA) and γH2AX as indices of proliferation and DNA damage, respectively.Results: The ketogenic diets combined with radiation resulted in slower tumor growth in both NCI-H292 and A549 xenografts (P < 0.05), relative to radiation alone. The ketogenic diet also slowed tumor growth when combined with carboplatin and radiation, relative to control. Tumors from animals fed a ketogenic diet in combination with radiation showed increases in oxidative damage mediated by lipid peroxidation as determined by 4HNE-modified proteins as well as decreased proliferation as assessed by decreased immunoreactive PCNA.Conclusions: These results show that a ketogenic diet enhances radio-chemo-therapy responses in lung cancer xenografts by a mechanism that may involve increased oxidative stress. Clin Cancer Res; 19(14); 3905–13. ©2013 AACR.

Background: Ventricular arrhythmia (VA) precipitating sudden cardiac arrest (SCD) is among the most frequent causes of death and pose a high burden on public health systems worldwide. The increasing availability of electrophysiological signals collected through conventional methods (e.g. electrocardiography (ECG)) and digital health technologies (e.g. wearable devices) in combination with novel predictive analytics using machine learning (ML) and deep learning (DL) hold potential for personalised predictions of arrhythmic events. Methods: This systematic review and exploratory meta-analysis assesses the state-of-the-art of ML/DL models of electrophysiological signals for personalised prediction of malignant VA or SCD, and studies potential causes of bias (PROSPERO, reference: CRD42021283464). Five electronic databases were searched to identify eligible studies. Pooled estimates of the diagnostic odds ratio (DOR) and summary area under the curve (AUROC) were calculated. Meta-analyses were performed separately for studies using publicly available, ad-hoc datasets, versus targeted clinical data acquisition. Studies were scored on risk of bias by the PROBAST tool. Findings: 2194 studies were identified of which 46 were included in the systematic review and 32 in the meta-analysis. Pooling of individual models demonstrated a summary AUROC of 0.856 (95% CI 0.755–0.909) for short-term (time-to-event up to 72 h) prediction and AUROC of 0.876 (95% CI 0.642–0.980) for long-term prediction (time-to-event up to years). While models developed on ad-hoc sets had higher pooled performance (AUROC 0.919, 95% CI 0.867–0.952), they had a high risk of bias related to the re-use and overlap of small ad-hoc datasets, choices of ML tool and a lack of external model validation. Interpretation: ML and DL models appear to accurately predict malignant VA and SCD. However, wide heterogeneity between studies, in part due to small ad-hoc datasets and choice of ML model, may reduce the ability to generalise and should be addressed in future studies. Funding: This publication is part of the project DEEP RISK ICD (with project number 452019308) of the research programme Rubicon which is (partly) financed by the Dutch Research Council ( NWO). This research is partly funded by the Amsterdam Cardiovascular Sciences (personal grant F.V.Y.T).

Background Drilling in neurosurgery is an integral part of surgical exposure, especially in skull base approaches and craniovertebral junction (CVJ) surgeries. Most of such drillings are done in close proximity to the neurovascular structures in skull base surgeries and cervical-medullary junction or facet/pedicle in CVJ surgeries. Reluctance to drilling among young neurosurgeons is due to less hands-on experience during training and also, in the early part of the career, due to fear of injury to neurovascular structures. Methods Five commonest bone removals for skull base region and CVJ surgeries that can be safely done using manual instruments were identified based on experiences of senior authors. The authors highlight key technical nuances to widen surgical corridors using manual instruments safely for skull base surgical approaches. Results Basic neuroanatomical concepts and basic physics help in using manual instruments safely for bone removals in various skull base surgical approaches. Conclusions Manual instruments may be used for bone removals in selected skull base surgical approaches, which help young neurosurgeons to perform these surgeries in limited-resource settings.

This work analyses the formation of the Knudsen layer in micro/nanoscale flows by linking a rough wall collision model to a continuum flow model via asymptotic matching. Expressions for the accommodation coefficients in terms of the surface characteristics are derived, allowing for boundary layer analysis of rarefied flows without the use of prior determined accommodation coefficients. This derived model, through use of the Lennard–Jones parameters for a nanoscale system, allows for a prediction of the the effective Tangential Momentum Accommodation Coefficient (TMAC) in flows against ordered nanoscale surfaces.

Shelf life of potato is highly variable depending upon various factors including nitrogen application and storage conditions. The perishable nature of potato tubers necessitates the study of factors affecting tuber post- harvest life. Objectives of this experiment were to study the influence of nitrogen doses on storage parameters of different potato varieties, viz., physiological loss in weight, decay loss and sprouting. The treatments consisted of four doses of nitrogen (control, 80, 160, and 240 kg ha-1) and three potato cultivars viz., Kufri Pukhraj, Kufri Gaurav and AICRP-P-39. After harvesting potatoes from the field, the tubers were cleaned and stored using a complete randomized design (CRD) and three replications, in a well-ventilated room for three months to assess their shelf life. The field application of 240 kg nitrogen per hectare resulted in the poor shelf life of tubers as compared to the ones grown under lower doses. However, the superior shelf life of potato tubers was observed under control during the whole storage period. Among the cultivars, Kufri Pukhraj had better storage quality than Kufri Gaurav and AICRP-P-39. Thus, to obtain maximum shelf life of potato tubers, the variety Kufri Pukhraj with no application of nitrogen is advisable.

The COVID-19 pandemic has forever affected healthcare and posed an incredible challenge to our society to care for our sick. Patients with cancer were found early on to have higher rates of complications with COVID-19. Radiation therapy is an integral part of treatment for many types of gynecologic cancer and adaptation on its utilization during the pandemic varied across the globe. In this review, we detail certain guidelines for the use of radiation in gynecologic cancers during the pandemic as well as real world accounts of how different countries adapted to these guidelines or created their own based on individualized resources, staffing, government restrictions, and societal norms. Critically, this review demonstrates the breadth of fractionation schemes and technologies used when resources were limited but highlights the importance of long term follow-up for many of our patients during this time.

Since the start of the COVID-19 pandemic, few studies have reported anaesthetic outcomes in parturients with SARS-CoV-2 infection. We reviewed the labour analgesic and anaesthetic interventions utilised in symptomatic and asymptomatic parturients who had a confirmed positive test for SARS-CoV-2 across 10 hospitals in the north-west of England between 1 April 2020 and 31 May 2021. Primary outcomes analysed included the analgesic/anaesthetic technique utilised for labour and caesarean birth. Secondary outcomes included a comparison of maternal characteristics, caesarean birth rate, maternal critical care admission rate along with adverse composite neonatal outcomes. A positive SARS-CoV-2 test was recorded in 836 parturients with 263 (31.4%) reported to have symptoms of COVID-19. Neuraxial labour analgesia was utilised in 104 (20.4%) of the 509 parturients who went on to have a vaginal birth. No differences in epidural analgesia rates were observed between symptomatic and asymptomatic parturients (OR 1.03, 95%CI 0.64-1.67; p = 0.90). The neuraxial anaesthesia rate in 310 parturients who underwent caesarean delivery was 94.2% (95%CI 90.6-96.0%). The rates of general anaesthesia were similar in symptomatic and asymptomatic parturients (6% vs. 5.7%; p = 0.52). Symptomatic parturients were more likely to be multiparous (OR 1.64, 95%CI 1.19-2.22; p = 0.002); of Asian ethnicity (OR 1.54, 1.04-2.28; p = 0.03); to deliver prematurely (OR 2.16, 95%CI 1.47-3.19; p = 0.001); have a higher caesarean birth rate (44.5% vs. 33.7%; OR 1.57, 95%CI 1.16-2.12; p = 0.008); and a higher critical care utilisation rate both pre- (8% vs. 0%, p = 0.001) and post-delivery (11% vs. 3.5%; OR 3.43, 95%CI 1.83-6.52; p = 0.001). Eight neonates tested positive for SARS-CoV-2 while no differences in adverse composite neonatal outcomes were observed between those born to symptomatic and asymptomatic mothers (25.8% vs. 23.8%; OR 1.11, 95%CI 0.78-1.57; p = 0.55). In women with COVID-19, non-neuraxial analgesic regimens were commonly utilised for labour while neuraxial anaesthesia was employed for the majority of caesarean births. Symptomatic women with COVID-19 are at increased risk of significant maternal morbidity including preterm birth, caesarean birth and peripartum critical care admission.

The quest to reduce transport resistance in separations using nanomaterials has led to considerable interest in nanoscale adsorbents and ultrathin membranes. It is now established that interfacial resistance limits the performance of such nanosized materials; however, the origin of this resistance is uncertain. While it is associated with surface pore blockages and distortions in some materials, its existence even in ideal materials is largely putative. Here, we report equilibrium molecular dynamics (EMD) simulations with ideal zeolite-based nanosheets, indicating the transport resistance to be entirely distributed within the solid, without contribution from an interfacial effect. We demonstrate the presence of an internal entry region over which fluid decorrelation occurs, and in which the local transport coefficient inside the crystal is nonuniform and position-dependent, increasing to the uniform value in the bulk material at larger distances. Our EMD-based diffusivity profiles within the nanomaterial enable us to unequivocally determine the entry length, and reveal an internal excess resistance, frequently assumed to be an interfacial resistance, due to significant reduction of the internal transport coefficient in the entrance and exit regions. A decrease in the entry length with loading in PON zeolite nanosheets is seen. We demonstrate a reduction in external resistance in the external bulk chambers used in simulations, triggered by the interplay of incomplete decorrelation in the nanosheet and periodic boundary conditions imposed on the system comprising the nanosheet and surrounding bulk reservoirs when the nanosheet thickness is less than the entry length. Our analysis of the transport dynamics within the nanosheet demonstrates that, at least for ideal systems, decomposition of the inhomogeneous diffusivity-based internal resistance into an interfacial and a uniform transport coefficient-based internal contribution is not appropriate for finite-sized systems. Our results will enable the improved design of nanoscale membranes and materials for applications in separation and other processes.