Years of life lost estimates cannot always be taken at face value: Response to “COVID-19 – exploring the implications of long-term condition type and extent of multimorbidity on years of life lost: a modelling study”

In their recent analysis, Hanlon et al. estimated the years of life lost (YLL) in people who have died with COVID-19 by following and expanding on the WHO standard approach. We welcome this research as an attempt to draw a more accurate picture of the mortality burden of this disease which has been involved in the deaths of more than 300,000 people worldwide as of May 2020. However, we argue that obtained YLL estimates (13 years for men and 11 years for women) are interpreted in a misleading way. Even with the presented efforts to control for the role of multimorbidity in COVID-19 deaths, these estimates cannot be interpreted to imply “how long someone who died from COVID-19 might otherwise have been expected to live”. By example we analyze the underlying problem which renders such an interpretation of YLL estimates impossible, and outline potential approaches to control for the problem.

Defence and unilateral action define US cybersecurity

Significance A recent analysis identified 96 pieces of cybersecurity legislation in the House of Representatives and 61 in the Senate as of December 2021. However, the federal government is moving slowly on changing regulation to boost cybersecurity of critical infrastructure. Impacts Bills to promote the development of the cybersecurity workforce enjoy broad bipartisan support, and are more likely to pass. Cryptocurrency traders should expect more oversight and regulation, especially on transparency requirements and anti-money laundering. Mandatory reporting requirements for ransomware and other types of cyberattacks are likely to be passed eventually. Critical infrastructure firms will face the greatest obligations to inform the government about their cybersecurity.

Numerical methods for the detection of phase defect structures in excitable media

Electrical waves that rotate in the heart organize dangerous cardiac arrhythmias. Finding the region around which such rotation occurs is one of the most important practical questions for arrhythmia management. For many years, the main method for finding such regions was so-called phase mapping, in which a continuous phase was assigned to points in the heart based on their excitation status and defining the rotation region as a point of phase singularity. Recent analysis, however, showed that in many rotation regimes there exist phase discontinuities and the region of rotation must be defined not as a point of phase singularity, but as a phase defect line. In this paper we use this novel methodology and perform comparative study of three different phase definitions applied to in-silico data and to experimental data obtained from optical voltage mapping experiments on monolayers of human atrial myocytes. We introduce new phase defect detection algorithms and compare them with those that appeared in literature already. We find that the phase definition is more important than the algorithm to identify sudden spatial phase variations. Sharp phase defect lines can be obtained from a phase derived from local activation times observed during one cycle of arrhythmia. Alternatively, similar quality can be obtained from a reparameterization of the classical phase obtained from observation of a single timeframe of transmembrane potential. We found that the phase defect line length was 35.9(62)mm in the Fenton-Karma model and 4.01(55)mm in cardiac human atrial myocyte monolayers. As local activation times are obtained during standard clinical cardiac mapping, the methods are also suitable to be applied to clinical datasets. All studied methods are publicly available and can be downloaded from an institutional web-server.

Classification of Bus Driving Behaviour In Universiti Malaysia Sabah Campus

Driving behaviour has been studied by numerous researchers for the past few years. It includes the instantaneous driving behaviour observations and the drivers speed which are said to be influenced by many factors, such as the demographic measure of the drivers, environmental, passenger effect, and road characteristics. This paper describes the recent analysis and classification of driver behaviour in actual driving scenarios among the bus drivers in Universiti Malaysia Sabah (UMS) Main Campus, Kota Kinabalu. This research focussed on determining the riderships of bus in UMS campus, to investigate the differences of instantaneous driving behaviours of bus drivers during the acceleration phase when leaving bus stops, and to poduce the classification of the bus driving behaviour in UMS based on the driver’s accelerations. In order to achieve the objective of this study, observations were made for determining the riderships and the differences in instantaneous bus driving behaviour several times for each bus stops. For drivers speed and accelerations, a mobile applications called Speedometer GPS was used to obtain the data. Interview was conducted to a total number of 10 respondents to obtain their demographic measure. The results obtained shows the ridership of UMS bus is the highest in the afternoon peak. The instantaneous driving behaviour produce the head movement as the highest percentage during peak hour, and inattentive behaviour as the highest during the off peak hour. The bus drivers in UMS were classified as Aggressive and Calm Behaviour Category.

Selective SGLT2 Inhibitor’s Estimation and Validation from Galenical Form by RP-HPLC Method

Aim: The recent analysis is required to do novel and simple, sensitive, precise, efficient, instant and reproducible reverse phase high performance liquid chromatography (RP-HPLC) method for estimation of antidiabetic drug in the unit dosage form. Validation of this method is also planned to make it suitable for the actual use. Study Design: Department of Pharmaceutical Chemistry, Datta Meghe Institute of Medical Sciences deemed to be university, Wardha in collaboration with Balkh university, Mazar-e-sharif, Afghanistan between August 2021 and December 2021. Methodology: In that article develop the method and validate it by estimation of antidiabetic drugs in solid dosage form by RP-HPLC, by using System suitability test, Repeatability, Precision studies (Intra-day and Interday/Intermediate), Linearity/Calibration studies, Robustness, Force degradation, Specificity, Drug recovery/accuracy studies. Results: as per ICH guidelines, the performance if system suitability in remogliflozin were achieved all guidelines; in that, tailing factor (T),separation factors(α),theoretical plates(N),capacity factor (k’), resolution (R) and RSD (%). The validated stress degradation studies under thermal, oxidative, alkali and acid, in few degradation products for remogliflozin (REM). Conclusion: From the results we conclude that, this novel technique which validated for exploration by reverse phase high performance liquid chromatography (RP-HPLC) should be used for routine quality control of remogliflozin (REM) prediction from developed formulation.

Significant cross-species gene flow detected in the Tamias quadrivittatus group of North American chipmunks

In the past two decades genomic data have been widely used to detect historical gene flow between species in a variety of plants and animals. The Tamias quadrivittatus group of North America chipmunks, which originated through a series of rapid speciation events, are known to undergo massive amounts of mitochondrial introgression. Yet in a recent analysis of targeted nuclear loci from the group, no evidence for cross-species introgression was detected, indicating widespread cytonuclear discordance. The study used heuristic methods that analyze summaries of the multilocus sequence data to detect gene flow, which may suffer from low power. Here we use the full likelihood method implemented in the Bayesian program BPP to reanalyze these data. We take a stepwise approach to constructing an introgression model by adding introgression events onto a well-supported binary species tree. The analysis detected robust evidence for multiple ancient introgression events affecting the nuclear genome, with introgression probabilities reaching 65%. We estimate population parameters and highlight the fact that species divergence times may be seriously underestimated if ancient cross-species gene flow is ignored in the analysis. Our analyses highlight the importance of using adequate statistical methods to reach reliable biological conclusions concerning cross-species gene flow.

Branching patterns of the afferent branchial arteries and their phylogenetic significance in rays (Batoidea)

Rays of the superorder Batoidea comprise the most diverse group of chondrichthyans in terms of valid species and morphological disparity. Up to the present little agreement is observed in studies based on morphological and molecular data focused on uncovering the interrelationships within Batoidea. Morphology-based phylogenies of batoids have not included characters related to the afferent branchial arteries, and little is known about the variation in this anatomical complex in rays. Herein, representatives of 32 genera from 19 families currently recognized of rays were examined as well as some shark taxa. Seven new characters are proposed and tested in two different analyses, one on their own and in the other they were added to the morphological data matrix of the most recent analysis of interrelationships within Batoidea. The arrangement of afferent branchial arteries differs mainly among orders and families of batoids. The absence of a common trunk from which the three posteriormost afferent arteries branch is interpreted as a synapomorphy for Myliobatiformes and the presence of a coronary cranial artery as an autapomorphy for Mobula hypostoma. A close spatial relationship between the second and third afferent arteries within the common branch from the ventral aorta is proposed as a synapomorphy for Rajiformes with a secondary modification in Sympterygia. Data about patterns in afferent branchial arteries in additional taxa such as Squaliformes and Chimaeriformes are needed to better understand the evolution of this character complex among chondrichthyans.

Characterization of Circulating Androgens, Cortisol and Estrogens During Normal, Abnormal and False Pregnancy in Bottlenose Dolphins (Tursiops truncatus) Under Managed Care

The few hormone studies on bottlenose dolphin (Tursiops truncatus) pregnancy with different reproductive outcomes, e.g., normal birth, stillbirth and abortion, have mostly focused on progestagens or relaxin. However, recent analysis of androgens, glucocorticoids and estrogens has shown they are also biomarkers of cetacean pregnancy. Therefore, our objective was to examine circulating concentrations of androgens, glucocorticoids and estrogens during bottlenose dolphin pregnancies with different reproductive outcomes, including normal pregnancy (NORM, n = 27), failure to thrive (FTT, n = 17), perinatal loss (PNL, n = 20), early loss (EL, n = 12) and false pregnancy (FP, n = 16), to determine if they could be potential indicators of reproductive or fetal health. We analyzed longitudinal serum samples (n = 654) from 57 bottlenose dolphins and 92 reproductive events for testosterone, androstenedione, cortisol, estradiol and estrone conjugates. Testosterone concentrations were higher during EL compared to NORM and lower during FP at MID (day 121 – 240 post ovulation/conception) and LATE (day 241 – end of FP) stages (months post conception/ovulation [MPC, MPO] seven through ten, P < 0.05). During FTT, androstenedione concentrations were increased compared to NORM pregnancies in the EARLY and LATE stages (P ≤ 0.05), and concentrations were reduced during FP (P < 0.05). For cortisol, FTT pregnancies had higher concentrations compared to NORM during all stages (P < 0.05), while PNL had higher cortisol during EARLY and LATE stages (P < 0.05). Estradiol concentrations were lower for EL and FP compared to NORM (P < 0.05), while estrone conjugates were only reduced during FP (P < 0.05). Based on our results only cortisol may be a useful predictor of PNL, while both cortisol and androstenedione were useful for distinguishing FTT pregnancies. Similarly, both testosterone and estradiol during EL and FP were different from NORM. Our data indicate a suite of pregnancy specific hormone biomarkers to evaluate maternal and fetal health in bottlenose dolphins should include cortisol, androgens and estrogens. This research also highlights the importance on non-progestagen hormones as sentinels of cetacean pregnancy and fetal health.

Current-Component Independent Transition Form Factors for Semileptonic and Rare D ⟶ π K Decays in the Light-Front Quark Model

We investigate the exclusive semileptonic and rare D ⟶ π K decays within the standard model together with the light-front quark model (LFQM) constrained by the variational principle for the QCD-motivated effective Hamiltonian. The form factors are obtained in the q + = 0 frame and then analytically continue to the physical timelike region. Together with our recent analysis of the current-component independent form factors f ± q 2 for the semileptonic decays, we present the current-component independent tensor form factor f T q 2 for the rare decays to make the complete set of hadronic matrix elements regulating the semileptonic and rare D ⟶ π K decays in our LFQM. The tensor form factor f T q 2 are obtained from two independent sets J T + ⊥ , J T + − of the tensor current J T u v . As in our recent analysis of f − q 2 , we show that f T q 2 obtained from the two different sets of the current components gives the identical result in the valence region of the q + = 0 frame without involving the explicit zero modes and the instantaneous contributions. The implications of the zero modes and the instantaneous contributions are also discussed in comparison between the manifestly covariant model and the standard LFQM. In our numerical calculations, we obtain the q 2 -dependent form factors ( f ± , f T ) for D ⟶ π K and branching ratios for the semileptonic D ⟶ π K ℓ v ℓ ℓ = e , μ decays. Our results show in good agreement with the available experimental data as well as other theoretical model predictions.

Effect of COVID-19 Pandemic Control Measures on Diagnoses of Hematologic Cancer Among CMS Population in 2020

Introduction Measures taken to mitigate infection spread during the 2020 COVID-19 pandemic are considered to have caused significant unintended consequences on other diseases. Large decreases in the numbers of symptomatic and asymptomatic people presenting for diagnosis of heart disease, diabetes and cancer have been observed. A recent analysis of solid tumors showed up to 70% reduction in the number of patients presenting for diagnosis. The potential exists for significantly increased morbidity and mortality for these missed or delayed presenting patients. Further, it is important to determine whether infection spread mitigation measures affected the diagnostic testing and treatment decisions for these patients. This study aimed to determine whether pandemic control measures affected presentation, testing and treatment of patients across eight different hematologic cancers. Methods CMS claims data were analyzed for the presence of diagnostic (DX) ICD 10 codes indicative of hematologic cancer. Patients with a DX code first appearing in 2019 or in 2020 were selected to provide newly diagnosed pre-COVID-19 and during COVID-19 cohorts for comparison, with unique patient counts being calculated for each month. A "COVID-19 dip" i.e. a decrease in the number of patients was calculated as the change in number of patients diagnosed in a given month relative to the number for JAN2020. Dip duration was calculated only when the decrease was >10% of the JAN2020 figure. Patients who received treatment via a "J" code Healthcare Common Procedure Coding System (HCPCS) code were extracted from the cohorts and the time taken from initial diagnosis to first treatment calculated. Results Eight hematologic cancers: AML, CLL, CML, HEME (a group of different hematologic cancers), Hodgkins (HOG), Myelodysplasia (MDS), Non-Follicular Lymphomas (NFL), and Non-Hodgkins Lymphoma (NHL) showed a decrease in the number of patients being diagnosed during the early part of 2020 (Fig.1) Fig.1. Change in new patient diagnoses for selected hematologic cancers as a proportion of their JAN2020 value There was some variation in the depth and duration of the COVID-19 dip (Table 1) with MDS having both the longest and deepest dip. Median depth and duration of the dip was 33% and 3.5 months, respectively, with all dips starting either in FEB or MAR2020. Table 1. Duration and depth of COVID-19 dips for selected hematological cancers The proportions of patients receiving therapy via J HCPCS code (JRX) are shown in Table 2 Table 2. Proportions of patients receiving J code therapy Conclusions The decline in new patient diagnoses for heme cancers during the period when COVID-19 control measures were implemented is similar to that seen with solid tumors, although the depth of the COVID-19 dip was generally larger in the latter. There is no evidence of "catch up" diagnosis occurring i.e. patients missing from Q2 2020 are not reappearing en masse in subsequent quarters. The decline for MDS patients has, except for SEP to OCT2020, remained. Collectively, (depending on the calculation method), the COVID-19 dip for these eight heme cancers represents 16,584-33,671 patients who will likely have significantly increased rates of morbidity and mortality due to delayed diagnosis. Analysis of J code treatments show little difference between the proportions of patients receiving these treatments in 2020 compared to 2019 suggesting that at least some aspects of treatment e.g. infused chemotherapy, IO drugs for these patients was relatively unchanged by pandemic control measures. It also suggests that the main cause for decreased patient numbers treated is due to decreased testing for diagnosis, rather than not being treated once diagnosed. This aligns with findings from studies in the US and UK. The results of this study indicate that there may be a "backlog" of tens of thousands of people with cancer whose diagnosis has been significantly delayed and who urgently need to be identified in order to get on proper treatment to lessen the impact of that delay. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.