Clinical implications of doubling time of gastrointestinal submucosal tumors

AIM To evaluate the efficacy of doubling time(DT) of gastrointestinal submucosal tumors(GIST).METHODS From April 1987 through November 2012, a total of 323 patients were given a final histopathological diagnosis of GISTs on surgical resection or endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA) in Kitasato University East Hospital or Kitasato University Hospital. We studied 53 of these patients(34 with resected tumors and 19 with unresected tumors) whose tumors could be measured on EUS on at least two successive occasions. The histopathological diagnosis was GIST in 34 patients, leiomyoma in 5, schwannoma in 3, ectopic pancreas in 1, hamartoma in 1, cyst in 1, Brunner's adenoma in 1, and spindle-cell tumor in 7. We retrospectively calculated the DT of GISTs on the basis of the time course of EUS findings to estimate the growth rate of such tumors.RESULTS The DT was 17.2 mo for GIST, as compared with 231.2 mo for leiomyoma, 104.7 mo for schwannoma, 274.9mo for ectopic pancreas, 61.2 mo for hamartoma, 49.0 mo for cyst, and 134.7 mo for Brunner's adenoma. The GISTs were divided into risk classes on the basis of tumor diameters and mitotic figures(Fletcher's classification). The classification was extremely low risk or low risk in 28 patients, intermediate risk in 3, and high risk in 3. DT of GIST according to risk was 24.0 mo for extremely low-risk plus low-risk GIST, 17.1 mo for intermediate-risk GIST, and 3.9 mo for high-risk GIST. DT of GIST was significantly shorter than that of leiomyoma plus schwannoma(P < 0.05), and DT of high-risk GIST was significantly shorter than that of extremely low-risk plus low-risk GIST(P < 0.05).CONCLUSION For GIST, a higher risk grade was associated with a significantly shorter DT. Small SMTs should initially be followed up within 6 mo after detection.

Prostate-specific antigen doubling time and response to cabazitaxel in a hormone-resistant metastatic prostate cancer patient

We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antigen doubling time and prostate-specific antigen absolute value. The prostate-specific antigen doubling time was found to be a good response predictor in the patient.

The Use of PSA Doubling Time to Predict Prognosis and the Use of PSA Response to Assess the Success for Prostate Cancer Patients Undergoing Docetaxel Chemotherapy

In the targeted therapy era, it is critical to know the certain points to start or discontinue chemotherapy for patients with castration resistant metastatic prostate cancer. The prognostic factors to determine this response are still not clear yet. We tried to find out if the PSA doubling time helps us to predict the patients who will benefit from docetaxel chemotherapy most, and also to question the value of the PSA response to chemotherapy. Retrospectively, 70 patients who had hormone refractory metastatic prostate cancer that were given at least 4 cycles of docetaxel chemotherapy between 2002 and 2015 were evaluated. After the onset of docetaxel, PSA response to therapy and overall survival rates were analyzed to figure out if these parameters were related to PSA doubling time. The only statistically significant prognostic parameter affecting overall survival was the best PSA response rate to docetaxel chemotherapy being over or under 50%. The most significant parameter that affects the PSA doubling time was the clinical stage at the time of diagnosis. PSA doubling time is not a useful predictive tool for predicting response to docetaxel. By means of overall survival, the clinical stage at the time of diagnosis was the best predictive tool for our cohort. The best PSA response rate to docetaxel chemotherapy was found to be a valuable parameter. The study being retrospective and the low number of patients included in this cohort can be the main weaknesses of this study. Further studies to determine which other factors can be useful are needed.

COVID-19 seeding time and doubling time model:an early epidemic risk assessment tool

Background:As COVID-19 makes its way around the globe,each nation must decide when and how to respond.Yet many knowledge gaps persist,and many countries lack the capacity to develop complex models to assess risk and response.This paper aimed to meet this need by developing a model that uses case reporting data as input and provides a four-tiered risk assessment output.Methods:We used publicly available,country/territory level case reporting data to determine median seeding number,mean seeding time(ST),and several measures of mean doubling time(DT)for COVID-19.We then structured our model as a coordinate plane with ST on the x-axis,DT on the y-axis,and mean ST and mean DT dividing the plane into four quadrants,each assigned a risk level.Sensitivity analysis was performed and countries/territories early in their outbreaks were assessed for risk.Results:Our main finding was that among 45 countries/territories evaluated,87%were at high risk for their outbreaks entering a rapid growth phase epidemic.We furthermore found that the model was sensitive to changes in DT,and that these changes were consistent with what is officially known of cases reported and control strategies implemented in those countries.Conclusions:Our main finding is that the ST/DT Model can be used to produce meaningful assessments of the risk of escalation in country/territory-level COVID-19 epidemics using only case reporting data.Our model can help support timely,decisive action at the national level as leaders and other decision makers face of the serious public health threat that is COVID-19.

Quantifying the natural growth rate of hepatocellular carcinoma:A real-world retrospective study in southwestern China

BACKGROUND In recent years,approximately half of the newly diagnosed cases and mortalities attributed to hepatocellular carcinoma(HCC)have been reported in China.Despite the high incidence of HCC,there remains a paucity of data regarding the natural growth pattern and the determination of optimal surveillance intervals specific to the Chinese population.AIM To quantify the natural tumor growth pattern of HCC in regional China.METHODS A retrospective analysis was performed on patients from a single institution in Southwest China who had undergone two or more serial dynamic computed tomography or magnetic resonance imaging scans between 2014 and 2020,without having received any anti-cancer therapy.Tumor growth was assessed using tumor volume doubling time(TVDT)and tumor growth rate(TGR),with volumes measured manually by experienced radiologists.Simple univariate linear regression and descriptive analysis were applied to explore associations between growth rates and clinical factors.RESULTS This study identifies the median TVDT for HCC as 163.4 d,interquartile range(IQR)72.1 to 302.3 d,with a daily TGR of 0.42%(IQR 0.206%-0.97%).HCC growth patterns reveal that about one-third of tumors grow indolently with TVDT exceeding 270 d,another one-third of tumors exhibit rapid growth with TVDT under 90 d,and the remaining tumors show intermediate growth rates,with TVDT ranging between 3 to 9 months.CONCLUSION The identified TGRs support biannual surveillance and follow-up for HCC patients in certain regions of China.Given the observed heterogeneity in HCC growth,further investigation is warranted.

Stability analysis of the active control system with time delay using IHB method

In this paper, the incremental harmonic balance method is employed to solve the periodic solution that a vibration active control system with double time delays generates, and the stability analysis of which is achieved by the Poincare theorem. The system stability regions can be obtained in view of time delay and feedback gain, the variation of which is also studied. It turns out that along with the increase of time delay, the active control system is not always from stable to unstable, and the system can be from stable to unstable state, whereas the system can be from unstable to stable state. The extent that the two times delays impact to the relative magnitude of the two feedback gains. the condition of the well-matched feedback gains. control strategy of time-delayed feedback.

Effect of reprocessing on neutrons of a molten chloride salt fast reactor

Due to their unique features,such as the inherent safety,simplified fuel cycle,and continuous on-line reprocessing,molten salt reactors(MSRs)are regarded as one of the six reference reactors in the Generation IV International Forum(GEN-IV).Molten chloride salt fast reactors(MCFRs)are a type of MSR.Compared to molten fluoride salt reactors(MFSRs),MCFRs have a higher solubility of heavy metal atoms,a harder neutron spectrum,lower accumulation of fission products(FPs),and better breeding and transmutation performance.Thus,MCFRs have been recognized as a type of MSR with great prospects for future development.However,as the most important feature for MSRs,the effect of different reprocessing modes on MCFRs must be researched in depth.As such,this study investigated the effect of different isotopes,especially FPs,on the neutronic performance of an MCFR,such as its breeding performance.Furthermore,the characteristics of the different reprocessing modes and MCFR rates were analyzed in terms of safety,radioactivity level,neutron economy,and breeding capacity.In the end,a reprocessing method suitable for MCFRs was determined through calculation and analysis,which provides a reference for the further research of MCFRs.

Cell cycle and radiosensitivity of progeny of irradiated primary cultured human hepatocarcinoma cells

AIM： To evaluate the change of growth characteristics and radiosensitivity of irradiated primary cultured human hepatocarcinoma cells. METHODS： All tumor tissue samples were obtained from 39 hepatocarcinoma patients with a mean age of 49.6 years （range 22-76 years）. We divided the samples into irradiated group and non-irradiated group and measured their plating efficiency （PE）, population doubling time （PDT）, radiosensitivity index SF2 and cell RESULTS： The PDT of primary culture of hepatocardnoma cells was 91.0±6.6 h, PE was 12.0±1.4%, SF2 was 0.41±0.05%. The PDT of their inadiated progeny was 124.8±5.8 h, PE was 5.0±0.7%, SF2 was 0.65±0.09%. The pdmary cultured human hepatocarcinoma cells showed significant S reduction and G^2 arrest in a dose-dependent manner. The progeny of irradiated primary cultured hepatocarcinoma cells grew more slowly and its radiosensitivity increased. CONCLUSION： The progeny of irradiated primary cultured human hepatocarcinoma cells grows more slowly and its radiosensitivity increases.

Th–U cycle performance analysis based on molten chloride salt and molten fluoride salt fast reactors

The recent development of molten salt fast reactors has generated a renewed interest in them. As compared to traditional solid fuel fast neutron systems, it has many unique advantages, e.g., lower fissile inventory,no initial criticality reserve, waste reduction, and a simplified fuel cycle. It has been recognized as an ideal reactor for achieving a closed Th–U cycle. Based on the carrier salt, molten salt fast reactors could be divided into either a molten chloride salt fast reactor(MCFR) or a molten fluoride salt fast reactor(MFFR);to compare their Th–U cycle performance, the neutronic parameters in a breeding and burning(B&B) transition scenario were studied based on similar core geometry and power. The results demonstrated that the required reprocessing rate for an MCFR to achieve self-breeding was lower than that of an MFFR.Moreover, the breeding capability of an MCFR was better than that of an MFFR;at a reprocessing rate of 40 L/day,using LEU and Pu as start-up fissile materials, the doubling time(DT) of an MFFR and MCFR were 88.0 years and 48.0 years, and 16.5 years and 16.2 years, respectively.Besides, an MCFR has lower radio-toxicity due to lower buildup of fission products(FPs) and transuranium(TRU),while an MFFR has a larger, delayed neutron fraction with smaller changes during the entire operation.

Growth process of small pancreatic carcinoma: A case report with imaging observation for 22 months

This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the low-echoic mass as a benign intraductal mucinous-papillary neoplasm (IPMN) based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.

Effect of Salinity on Growth of Mussels,Mytilus edulis,with Special Reference to Great Belt(Denmark)

The effects of salinities between 10 and 30 psu on the growth of blue mussels, Mytilus edulis, were studied in laboratory feeding experiments and compared to the growth of mussels suspended in net-bags in the brackish water Great Belt, Denmark. In the laboratory, 3 series of growth experiments were conducted: in Series #1, groups of mussels were exposed to 10, 15, 25 and 30 psu, in Series #2, two groups of mussels were exposed to 10 and 30 psu, respectively, for 15 days (first period) where upon the mussels were exposed to the reversed salinities for another 15 days (second period). In Series #3, two groups of mussels were initially exposed to 15 and 25 psu for 22 days whereupon the mussel groups were exposed to the reversed salinities for another 17 days. In the laboratory experiments there was a tendency towards reduced growth with decreasing salinity, reflected as reduced shell growth rate and decreasing weight specific growth rate with falling salinity. The shell growth rate was relatively low in the first feeding period compared to the second period, and mussels that were initially exposed to 10 psu, where the growth was low, exhibited fast growth when subsequently exposed to 30 psu, and reversed when 30 psu mussels were exposed to 10 psu. The study showed that mussels are able to adjust growth at changing salinities, and the observed effect of salinity could partly be explained by a temporary shell valve closure after a sudden change in salinity. The specific growth rate of mussels measured in laboratory experiments at salinities between 15 to 25 psu (4.2% to 4.8% d–1) were comparable to the growth of mussels in the field experiment (3.2% to 4.0% d–1) where the salinity varied between 24 and 13 psu during the growth period.

Rapid killer:Lung squamous cell cancer

Background:Lung cancer is one of the leading causes of death despite improvement in treatment modalities such as immunotherapy with chemotherapy and precise radiotherapy.NSCLC is a heterogeneous group of diseases that differs in cytology and includes adenocarcinoma,squamous cell carcinoma,bronchioloalveolar carcinoma,and poorly differentiated carcinoma.Usually,NSCLC,in contrast to SCLC,spreads locally,and the doubling time of squamous cell carcinoma is 133 days which classifies it as a relatively slow-growing tumor.Case presentation:We present the case of a 72-year-old male,recently diagnosed with squamous cell carcinoma in the right upper lobe along with secondary deposits.Few days after diagnosis,the patient had severe respiratory distress.This endobronchial tumor has increased significantly in size upon bronchoscopic visualization causing a complete obstruction of his right main bronchus and hypoxemic respiratory failure requiring intubation.Conclusion:To our knowledge,there are few reported cases where lung adenocarcinoma progressed rapidly over days.Squamous cell carcinoma usually takes 3 to 6 months to double in size,but in our case,the progression was very fast.In the last decade,it was confirmed that the doubling time of a tumor is an independent factor in the prognosis of lung cancer patients.On the other hand,further studies are needed to identify genes associated with rapid progression and a worse prognosis for lung squamous cell carcinoma.Hence,this aggressive tumor is a“rapid killer.”

Effects of LiAl-Layered Double Hydroxides on Early Hydration of Calcium Sulphoaluminate Cement Paste

As a 3D micro-nano material, layered double hydroxides have been widely used in many fields, especially for reinforced composite materials. In this paper, Li Al-LDHs was obtained by a hydrothermal method. In order to investigate the effects of Li Al-LDHs on the early hydration of calcium sulphoaluminate（CSA） cement paste, compressive strength, setting time and hydration heat were tested while X-ray diffraction（XRD）, Fourier transform infrared spectroscopy（FT-IR）, scaning electron microscopy（SEM） and differential scanning calorimetry（DSC） analysis were employed. The results indicated that Li Al-LDHs could significantly improve the early compressive strength and shorten the setting time of calcium sulphoaluminate cement paste with 3 wt% concentration. Besides, the hydration exothermic rate within 5h was accelerated with increasing Li Al-LDHs content. Moreover, the addition of Li Al-LDHs did not result in the formation of a new phase, but increased the quantity of hydration products providing higher compressive strength, shorter setting time and denser microstructure.

Implementation of a real-time, data-driven online Epidemic Calculator for tracking the spread of COVID-19 in Singapore and other countries

While there are many online data dashboards on COVID-19,there are few analytics available to the public and non-epidemiologists to help them gain a deeper insight into the COVID-19 pandemic and evaluate the effectiveness of social intervention measures.To address the issue,this study describes the methods underlying the development of a realtime,data-driven online Epidemic Calculator for tracking COVID-19 growth parameters.From publicly available infection case and death data,the calculator is used to estimate the effective reproduction number,final epidemic size,and death toll.As a case study,we analyzed the results for Singapore during the"Circuit Breaker"period from April 7,2020 to the end of May 2020.The calculator shows that the stringent measures imposed have an immediate effect of rapidly slowing down the spread of the coronavirus.After about two weeks,the effective reproduction number reduced to about 1.0.Since then,the number has been fluctuating around 1.0 for more than a month.The COVID-19 Epidemic Calculator is available in the form of an online Google Sheet and the results are presented as Tableau Public dashboards at www.cv19.one.By making the calculator readily accessible online,the public can have a tool to assess the effectiveness of measures to control the pandemic meaningfully.

Sensitivity of UK Covid-19 deaths to the timing of suppression measures and their relaxation

In this paper I examine the sensitivity of total UK Covid-19 deaths and the demand for intensive care and ward beds,to the timing and duration of suppression periods during a 500-day period.This is achieved via a SEIR model.Using an expected latent period of 4.5 days and infectious period of 3.8 days,R0 was first estimated as 3.18 using observed death rates under unmitigated spread and then under the effects of the total lockdown(R0-0.60)beginning 23 March.The case fatality rate given infection is taken as 1%.Parameter values for mean length of stay and conditional probability of death for ICU and non-ICU hospital admissions are guided by Ferguson et al.(2020).Under unmitigated spread the model predicts around 600,000 deaths in the UK.Starting with one exposed person at time zero and a suppression consistent with an R0 of 0.60 on day 72,the model predicts around 39,000 deaths for a first wave,but this reduces to around 11,000 if the intervention takes place one week earlier.If the initial suppression were in place until day 200 and then relaxed to an R0 of 1.5 between days 200 and 300,to be followed by a return to an R0 of 0.60,the model predicts around 43,000 deaths.This would increase to around 64,000 if the release from the first suppression takes place 20 days earlier.The results indicate the extreme sensitivity to timing and the consequences of even small delays to suppression and premature relaxation of such measures.

Human condition monitoring in hazardous locations using pervasive RFID sensor tags and energy-efficient wireless networks

Tracking persons in dangerous situations as well as monitoring their physical condition, is often crucial for their safety. The systems commonly used for this purpose do not include individual monitoring or are too expensive and intrusive to be deployed in common situations. In this project, a mobile system based on energy-efficient wireless sensor networks (WSNs) and active radio frequency identification (RFID) has been developed to achieve ubiquitous positioning and monitoring of people in hazardous situations. The system designed can identify each individual, locate him/her, send data regarding their physical situation, and ascertain whether they are located in a confined space. A new algorithm called time division double beacon scheduling (TDDBS) has been implemented to increase operation time and data transmission rate of the nodes in the system. The results show that the use of this system allows us to find the location and state of a person, as well as to provide an analysis of the potential risks at each moment, in real time and in an energy-efficient way. In an emergency, the system also allows for quicker intervention, as it not only provides the location and causes of the event, but also informs about the physical condition of the individual at that moment.

A Special MJO Event with a Double Kelvin Wave Structure

The second Madden–Julian Oscillation（MJO）event during the field campaign of the Dynamics of the MJO/Cooperative Indian Ocean Experiment on Intraseasonal Variability in the Year 2011（DYNAMO/CINDY2011）exhibi ted an unusual double rainband structure.Using a wavenumber-frequency spectral filtering method,we unveil that this double rainband structure arises primarily from the Kelvin wave component.The zonal phase speed of the double rainbands is about 7.9 degree per day in the equatorial Indian Ocean,being in the range of convectively coupled Kelvin wave phase speeds.The convection and circulation anomalies associated with the Kelvin wave component are characterized by two anomalous convective cells,with low-level westerly（easterly）and high（low）pressure anomalies to the west（east）of the convective centers,and opposite wind and pressure anomalies in the upper troposphere.Such a zonal wind–pressure phase relationship is consistent with the equatorial free-wave dynamics.While the freeatmospheric circulation was dominated by the first baroclinic mode vertical structure,moisture and vertical motion in the boundary layer led the convection.The convection and circulation structures derived based on the conventional MJO filter show a different characteristic.For example,the phase speed is slower（about 5.9 degree per day）,and there were no double convective branches.This suggests that MJO generally involves multi-scales and it is incomplete to extract its signals by using the conventional filtering technique.