Estimating effective reproduction number revisited.

Accurately estimating the effective reproduction number is crucial for characterizing the transmissibility of infectious diseases to optimize interventions and responses during epidemic outbreaks. In this study, we improve the estimation of the effective reproduction number through two main approaches. First, we derive a discrete model to represent a time series of case counts and propose an estimation method based on this framework. We also conduct numerical experiments to demonstrate the effectiveness of the proposed discretization scheme. By doing so, we enhance the accuracy of approximating the underlying epidemic process compared to previous methods, even when the counting period is similar to the mean generation time of an infectious disease. Second, we employ a negative binomial distribution to model the variability of count data to accommodate overdispersion. Specifically, given that observed incidence counts follow a negative binomial distribution, the posterior distribution of secondary infections is obtained as a Dirichlet multinomial distribution. With this formulation, we establish posterior uncertainty bounds for the effective reproduction number. Finally, we demonstrate the effectiveness of the proposed method using incidence data from the COVID-19 pandemic.

Multivariate epidemic count time series model.

An infectious disease spreads not only over a single population or community but also across multiple and heterogeneous communities. Moreover, its transmissibility varies over time because of various factors such as seasonality and epidemic control, which results in strongly nonstationary behavior. In conventional methods for assessing transmissibility trends or changes, univariate time-varying reproduction numbers are calculated without taking into account transmission across multiple communities. In this paper, we propose a multivariate-count time series model for epidemics. We also propose a statistical method for estimating the transmission of infections across multiple communities and the time-varying reproduction numbers of each community simultaneously from a multivariate time series of case counts. We apply our method to incidence data for the novel coronavirus disease 2019 (COVID-19) pandemic to reveal the spatiotemporal heterogeneity of the epidemic process.

Perioperative Serum Creatinine Change and Delayed Urologic Complications Following Total Laparoscopic Hysterectomy for Benign Indications.

Objectives: The objective of the study was to investigate the association between perioperative serum creatinine change and delayed urologic complications following total laparoscopic hysterectomy (TLH) for benign indications. Materials and Methods: A total of 510 cases (503 cases without delayed urologic injuries and 7 cases with delayed urologic injuries) in which TLH was performed for benign indications were retrospectively reviewed. The patient characteristics and surgical outcomes were compared between patients with and without delayed urologic injuries. Laboratory markers (serum creatinine level at the preoperative and postoperative periods, white blood cell [WBC] ratio, and C-reactive protein [CRP] ratio) were analyzed to evaluate the diagnostic value of these laboratory markers. Results: There were no statistically significant differences in age, parity, body mass index, the presence of diabetes mellitus, preoperative GnRH agonist use, previous history of abdominal surgery or the performance of adnexal surgery, ASRM score, the presence of cul-de-sac obliteration, operative time, blood loss or weight of the resected specimens between the two groups. The proportions of patients who showed an elevated creatinine level on postoperative day 1 was significantly higher in the delayed urologic injury group (9.9% vs. 57%, P < 0.001). The combination of the three laboratory markers yielded an area under the ROC curve value of 0.75 (95% confidence interval, 0.491-1) in the detection of delayed urologic injuries. Conclusion: A change in the serum creatine level over baseline after surgery may indicate the possibility of urologic injuries. The combination of creatinine change and other factors, such as WBC or CRP would be helpful for detecting urologic complications after TLH.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Estimating the time-varying reproduction number of COVID-19 with a state-space method.

After slowing down the spread of the novel coronavirus COVID-19, many countries have started to relax their confinement measures in the face of critical damage to socioeconomic structures. At this stage, it is desirable to monitor the degree to which political measures or social affairs have exerted influence on the spread of disease. Though it is difficult to trace back individual transmission of infections whose incubation periods are long and highly variable, estimating the average spreading rate is possible if a proper mathematical model can be devised to analyze daily event-occurrences. To render an accurate assessment, we have devised a state-space method for fitting a discrete-time variant of the Hawkes process to a given dataset of daily confirmed cases. The proposed method detects changes occurring in each country and assesses the impact of social events in terms of the temporally varying reproduction number, which corresponds to the average number of cases directly caused by a single infected case. Moreover, the proposed method can be used to predict the possible consequences of alternative political measures. This information can serve as a reference for behavioral guidelines that should be adopted according to the varying risk of infection.

Statistical inference of the rate of RNA polymerase II elongation by total RNA sequencing.

MOTIVATION: Sequencing total RNA without poly-A selection enables us to obtain a transcriptomic profile of nascent RNAs undergoing transcription with co-transcriptional splicing. In general, the RNA-seq reads exhibit a sawtooth pattern in a gene, which is characterized by a monotonically decreasing gradient across introns in the 5'-3' direction, and by substantially higher levels of RNA-seq reads present in exonic regions. Such patterns result from the process of underlying transcription elongation by RNA polymerase II, which traverses the DNA strand in a 5'-3' direction as it performs a complex series of mRNA synthesis and processing. Therefore, data of sequenced total RNAs could be utilized to infer the rate of transcription elongation by solving the inverse problem. RESULTS: Though solving the inverse problem in total RNA-seq has the great potential, statistical methods have not yet been fully developed. We demonstrate what extent the newly developed method can be useful. The objective is to reconstruct the spatial distribution of transcription elongation rates in a gene from a given noisy, sawtooth-like profile. It is necessary to recover the signal source of the elongation rates separately from several types of nuisance factors, such as unobserved modes of co-transcriptionally occurring mRNA splicing, which exert significant influences on the sawtooth shape. The present method was tested using published total RNA-seq data derived from mouse embryonic stem cells. We investigated the spatial characteristics of the estimated elongation rates, focusing especially on the relation to promoter-proximal pausing of RNA polymerase II, nucleosome occupancy and histone modification patterns. AVAILABILITY AND IMPLEMENTATION: A C implementation of PolSter and sample data are available at https://github.com/yoshida-lab/PolSter. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Length of myelin internodes of individual oligodendrocytes is controlled by microenvironment influenced by normal and input-deprived axonal activities in sensory deprived mouse models.

Oligodendrocytes myelinate neuronal axons to increase conduction velocity in the vertebrate central nervous system (CNS). Recent studies revealed that myelin formed on highly active axons is more stable compared to activity-silenced axons, and length of the myelin sheath is longer in active axons as well in the zebrafish larva. However, it is unclear whether oligodendrocytes preferentially myelinate active axons compared to sensory input-deprived axons in the adult mammalian CNS. It is also unknown if a single oligodendrocyte forms both longer myelin sheaths on active axons and shorter sheaths on input-deprived axons after long-term sensory deprivation. To address these questions, we applied simultaneous labeling of both neuronal axons and oligodendrocytes to mouse models of long-term monocular eyelid suturing and unilateral whisker removal. We found that individual oligodendrocytes evenly myelinated normal and input-deprived axons in the adult mouse CNS, and myelin sheath length on normal axons and input-deprived axons formed by a single oligodendrocyte were comparable. Importantly, the average length of the myelin sheath formed by individual oligodendrocytes did change depending on relative abundance of normal against sensory-input deprived axons, indicating an abundance of deprived axons near an oligodendrocyte impacts on myelination program by a single oligodendrocyte.

Remote reprogramming of hepatic circadian transcriptome by breast cancer.

Cancers adversely affect organismal physiology. To date, the genes within a patient responsible for systemically spreading cancer-induced physiological disruption remain elusive. To identify host genes responsible for transmitting disruptive, cancer-driven signals, we thoroughly analyzed the transcriptome of a suite of host organs from mice bearing 4T1 breast cancer, and discovered complexly rewired patterns of circadian gene expression in the liver. Our data revealed that 7 core clock transcription factors, represented by Rev-erba and Rorg, exhibited abnormal daily expression rhythm in the liver of 4T1-bearing mice. Accordingly, expression patterns of specific set of downstream circadian genes were compromised. Osgin1, a marker for oxidative stress, was an example. Specific downstream genes, including E2f8, a transcriptional repressor that controls cellular polyploidy, displayed a striking pattern of disruption, "day-night reversal." Meanwhile, we found that the liver of 4T1-bearing mice suffered from increased oxidative stress. The tetraploid hepatocytes population was concomitantly increased in 4T1-bearing mice, which has not been previously appreciated as a cancer-induced phenotype. In summary, the current study provides a comprehensive characterization of the 4T1-affected hepatic circadian transcriptome that possibly underlies cancer-induced physiological alteration in the liver.

Rabies virus-mediated oligodendrocyte labeling reveals a single oligodendrocyte myelinates axons from distinct brain regions.

Oligodendrocytes myelinate neuronal axons during development and increase conduction velocity of neuronal impulses in the central nervous system. Neuronal axons extend from multiple brain regions and pass through the white matter; however, whether oligodendrocytes ensheath a particular set of axons or do so randomly within the mammalian brain remains unclear. We developed a novel method to visualize individual oligodendrocytes and axon derived from a particular brain region in mouse white matter using a combinational injection of attenuated rabies virus and adeno-associated virus. Using this method, we found that some populations of oligodendrocytes in the corpus callosum predominantly ensheathed axons derived from motor cortex or sensory cortex, while others ensheathed axons from both brain regions, suggesting heterogeneity in preference of myelination toward a particular subtype of neurons. Moreover, our newly established method is a versatile tool for analyzing precise morphology of each oligodendrocyte in animal models for demyelinating disorders and addressing the role of oligodendrocyte in higher brain functions. GLIA 2016. GLIA 2017;65:93-105.

Fluctuation scaling in neural spike trains.

Fluctuation scaling has been observed universally in a wide variety of phenomena. In time series that describe sequences of events, fluctuation scaling is expressed as power function relationships between the mean and variance of either inter-event intervals or counting statistics, depending on measurement variables. In this article, fluctuation scaling has been formulated for a series of events in which scaling laws in the inter-event intervals and counting statistics were related. We have considered the first-passage time of an Ornstein-Uhlenbeck process and used a conductance-based neuron model with excitatory and inhibitory synaptic inputs to demonstrate the emergence of fluctuation scaling with various exponents, depending on the input regimes and the ratio between excitation and inhibition. Furthermore, we have discussed the possible implication of these results in the context of neural coding.

Post-partum hypoglycemia and hypothermia as first manifestations of lymphocytic adenohypophysitis: A case report.

Lymphocytic adenohypophysitis is a very rare autoimmune disease characterized by an anterior pituitary infiltration of lymphocytes that cause various symptoms, such as headache, visual disturbance, and hypopituitarism. Lymphocytic adenohypophysitis is more common in women and has a remarkable association with the perinatal period. Recently, we experienced a case of lymphocytic adenohypophysitis shortly after delivery. A 37-year-old primiparous woman delivered her baby at 38 weeks' gestation. The next morning, she presented symptoms of hypoglycemia and hypothermia. Blood testing revealed hypoadrenalism and hypothyroidism. Pituitary magnetic resonance imaging showed characteristic findings consistent with lymphocytic adenohypophysitis. We immediately initiated medication with steroids and levothyroxine. Currently, her pituitary size has normalized and its function has fully recovered. Physical stress resulting from labor and delivery may unmask subclinical lymphocytic adenohypophysitis. Practitioners should keep in mind the possibility of lymphocytic adenohypophysitis in any pregnant women with symptoms of hypoglycemia and hypothermia after delivery.

On the Spike Train Variability Characterized by Variance-to-Mean Power Relationship.

We propose a statistical method for modeling the non-Poisson variability of spike trains observed in a wide range of brain regions. Central to our approach is the assumption that the variance and the mean of interspike intervals are related by a power function characterized by two parameters: the scale factor and exponent. It is shown that this single assumption allows the variability of spike trains to have an arbitrary scale and various dependencies on the firing rate in the spike count statistics, as well as in the interval statistics, depending on the two parameters of the power function. We also propose a statistical model for spike trains that exhibits the variance-to-mean power relationship. Based on this, a maximum likelihood method is developed for inferring the parameters from rate-modulated spike trains. The proposed method is illustrated on simulated and experimental spike trains.

Abnormal pressure-wave reflection in pregnant women with chronic hypertension: association with maternal and fetal outcomes.

The current study tested the hypothesis that abnormal pressure-wave reflection may have an important role in identifying pregnant women with chronic hypertension who might develop pre-eclampsia (PE) and/or fetal growth restriction. Pulse-wave analyses were performed to assess maternal arterial stiffness during 26-32 weeks of gestation in 41 women with chronic hypertension. We measured the central systolic pressure (CSP) and augmentation index (AIx) noninvasively using pulse waveforms of the radial artery with an automated applanation tonometric system. In a multiple regression analysis that included AIx-75 (AIx at a heart rate of 75 beats per minute), brachial systolic pressure, maternal height, smoking status, gestational age at testing and the presence of antihypertensive treatment at testing as independent determinants, AIx-75 was the only significant determinant of birth weight, whereas the brachial systolic pressure was not. In pregnant women with chronic hypertension who subsequently developed both superimposed PE and fetal growth restriction, CSP, AIx, AIx-75, and the brachial systolic and pulse pressures were all significantly higher than those who did not develop superimposed PE nor small for gestational age. In contrast, AIx-75 was the only significantly elevated hemodynamic parameter in patients who developed fetal growth restriction but not superimposed PE. In addition, CSP was the only significantly elevated hemodynamic parameter in patients who developed superimposed PE but not fetal growth restriction. Abnormal pressure-wave reflection during 26-32 weeks of gestation showed a stronger correlation with birth weight than conventional brachial blood pressure. Our findings might provide new insight into the pathophysiology of fetal growth restriction as well as superimposed PE in pregnancies complicated with chronic hypertension.

Hand-assisted laparoscopic surgery for a mesenteric teratoma.

Mature cystic teratomas are benign neoplasms of germ cell tumors that occur most frequently in gonadal sites. The tumors usually contain 2 or 3 well-differentiated elements of endodermal, ectodermal, and mesodermal origin. Although relatively uncommon, teratomas can be composed of mature tissue originating from only 1 germ cell layer. This is known as a monodermal teratoma. Extragonadal teratomas, especially mesenteric teratomas, are extremely rare. Currently, only 21 cases of mesenteric teratoma have been described in the English literature. Mesenteric teratomas are rarely diagnosed preoperatively because pathological examination is necessary to make a definitive diagnosis. We herein report a rare case of mesenteric monodermal teratoma and review the literature. To the best of our knowledge, this is the first case of mesenteric teratoma treated with hand-assisted laparoscopic surgery.

Anorectal abscess during pregnancy.

Anorectal symptoms and complaints caused by hemorrhoids or anal fissures are common during pregnancy. It is known that one-third of pregnant women complain of anal pain in the third trimester. Anal pain may be caused by a wide spectrum of conditions, but if it begins gradually and becomes excruciating within a few days it may indicate anorectal abscess. We experienced a case of anorectal abscess during pregnancy which was diagnosed by magnetic resonance imaging and treated by incision and seton drainage at 36 weeks of gestation, followed by a normal spontaneous delivery at 38 weeks of gestation. To our knowledge, this is the first case report of anorectal abscess during pregnancy in the English-language published work. The clinical course of our case and clinical considerations of anorectal abscesses are discussed.

The effect of interspike interval statistics on the information gain under the rate coding hypothesis.

The question, how much information can be theoretically gained from variable neuronal firing rate with respect to constant average firing rate is investigated. We employ the statistical concept of information based on the Kullback-Leibler divergence, and assume rate-modulated renewal processes as a model of spike trains. We show that if the firing rate variation is sufficiently small and slow (with respect to the mean interspike interval), the information gain can be expressed by the Fisher information. Furthermore, under certain assumptions, the smallest possible information gain is provided by gamma-distributed interspike intervals. The methodology is illustrated and discussed on several different statistical models of neuronal activity.

Laparoscopic repair of a post-myomectomy spontaneous uterine perforation accompanied by a bizarre tumor resembling polypoid endometriosis.

Among various long-term complications after previous myomectomy, increasing risk of uterine rupture or dehiscence during pregnancy, and in particular during labor, has been widely recognized. In contrast, the world literature includes no case report of spontaneous uterine perforation or rupture after myomectomy in a nonpregnant woman, and only 1 case of iatrogenic uterine perforation after uterine artery embolization has been reported. Recently, we encountered an extremely rare case of spontaneous uterine perforation after previous myomectomy accompanied by a bizarre tumor resembling polypoid endometriosis, which was successfully treated via laparoscopic surgery. The patient reported genital bleeding and lower abdominal pain. Preoperative magnetic resonance imaging and intraoperative findings clearly demonstrated the presence of a uterine wall defect and a multicystic tumor that had developed from the perforated portion of the uterus. The patient underwent successful laparoscopic surgery for repair of the perforated uterus and resection of the tumor. The clinicopathologic diagnosis of the tumor was tentatively confirmed as an endometriosis-like lesion resembling polypoid endometriosis. We speculate that the cause of the tumor was retrograde menstruation, as in the pathogenesis of endometriosis.

Neural networks using two-component Bose-Einstein condensates.

The authors previously considered a method of solving optimization problems by using a system of interconnected network of two component Bose-Einstein condensates (Byrnes, Yan, Yamamoto New J. Phys. 13, 113025 (2011)). The use of bosonic particles gives a reduced time proportional to the number of bosons N for solving Ising model Hamiltonians by taking advantage of enhanced bosonic cooling rates. Here we consider the same system in terms of neural networks. We find that up to the accelerated cooling of the bosons the previously proposed system is equivalent to a stochastic continuous Hopfield network. This makes it clear that the BEC network is a physical realization of a simulated annealing algorithm, with an additional speedup due to bosonic enhancement. We discuss the BEC network in terms of neural network tasks such as learning and pattern recognition and find that the latter process may be accelerated by a factor of N.

Rupture of renal artery aneurysm during the early post-partum period.

Rupture of renal artery aneurysm associated with pregnancy is an uncommon condition. It is known that almost all previously reported cases have occurred during pregnancy. We experienced a case of rupture of renal artery aneurysm during the early post-partum period which was diagnosed by computed tomography and treated by angiographic embolization. To our knowledge, only two cases of rupture of renal artery aneurysm during the post-partum period have been reported in the English-language published work. An early diagnosis of rupture of renal artery aneurysm during the post-partum period is very challenging because the clinical symptoms of this condition are acute abdominal, flank or back pain, which are relatively common signs caused by more common post-partum complications. However, rupture of renal artery aneurysm is a life-threatening emergency condition requiring prompt diagnosis and treatment. The possibility of a rupture of renal artery aneurysm should be considered in any pregnant women with symptoms of an acute abdomen with hemorrhagic shock.

Angiographic findings after vaginal gauze packing: New insight into an old technique.

We had a transferred case of cervical ectopic pregnancy with hemorrhagic shock at 6 weeks of gestation. Upon arrival at hospital, we performed tight and full vaginal gauze packing to push the uterus upward to control the patient's hemorrhage. Following stabilization of her general condition, she was treated with uterine artery embolization. Using angiography, the effectiveness of vaginal gauze packing for emergency hemostasis by the presumed mechanism of impairing blood flow through the uterine artery was demonstrated. To our knowledge, there are no reports that have previously demonstrated angiographic findings similar to ours after vaginal gauze packing. Vaginal gauze packing is an effective, rapid, and convenient hemostatic procedure able to be carried out in a time-sensitive and challenging situation. As a result, this procedure gives clinicians more time to improve the patients' general status and arrange for transfusion and further definitive treatment.