Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

Background CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer. Results Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone. Conclusion Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.

Effects of vaccination and non-pharmaceutical interventions and their lag times on the COVID-19 pandemic: Comparison of eight countries

Many countries implemented measures to control the COVID-19 pandemic, but the effects of these measures have varied greatly. We evaluated the effects of different policies, the prevalence of dominant variants (e.g., Delta), and vaccination on the characteristics of the COVID-19 pandemic in eight countries. We quantified the lag times of different non-pharmaceutical interventions (NPIs) and vaccination using a distributed lag non-linear model (DLNM). We also tested whether these lag times were reasonable by analyzing changes in daily cases and the effective reproductive number (Rt)over time. Our results indicated that the response to vaccination in countries with continuous vaccination programs lagged by at least 40 days, and the lag time for a response to NPIs was at least 14 days. A rebound was most likely to occur during the 40 days after the first vaccine dose. We also found that the combination of school closure, workplace closure, restrictions on mass gatherings, and stay-at-home requirements were successful in containing the pandemic. Our results thus demonstrated that vaccination was effective, although some regions were adversely affected by new variants and low vaccination coverage. Importantly, relaxation of NPIs soon after implementation of a vaccination program may lead to a rebound.

A Hydrofracturing-Triggered Earthquake Occurred Three Years after the Stimulation

Hydrofracturing, used for shale gas exploitation, may induce felt, even damaging earthquakes. On 15 June 2019, an Mw2.8 earthquake occurred, spatially correlated with the location of earlier exploratory hydrofracturing operations for shale gas in Wysin in Poland. However, this earthquake was atypical. Hydrofracturing-triggered seismicity mainly occurs during stimulation; occasionally, it continues a few months after completion of the stimulation. In Wysin, there were only two weaker events during two-month hydrofracturing and then 35 months of seismic silence until the mentioned earthquake occurred. The Wysin site is in Gdańsk Pomerania broader region, located on the very weakly seismically active Precambrian Platform. The historical documents, covering 1000 years, report no natural earthquakes in Gdańsk Pomerania. We conclude, therefore, that despite the never observed before that long lag time after stimulation, the Mw2.8 earthquake was triggered by hydrofracturing. It is possible that its unusually late occurrence in relation to the time of its triggering technological activity was caused by changes in stresses due to time-dependent deformation of reservoir shales. The Wysin earthquake determines a new time horizon for the effect of HF on the stress state, which can lead to triggering earthquakes. Time-dependent deformation and its induced stress changes should be considered in shall gas reservoir exploitation plans.

Effects of housing environment on oral absorption of acetaminophen in healthy Beagles

OBJECTIVE To evaluate the effects of housing environment on oral absorption of acetaminophen in dogs. ANIMALS 6 healthy Beagles. PROCEDURES Acetaminophen (325 mg, PO; mean dose, 31.1 mg/kg) was administered in a crossover study design with dogs housed in their normal environment or in a cage in an unfamiliar environment. There was a 7-day washout period between phases. Blood samples were collected for 24 hours following acetaminophen administration, and plasma acetaminophen concentrations were determined with high-pressure liquid chromatography. RESULTS A 2-compartment model with lag time was the best fit for both phases of the study. None of the primary or secondary pharmacokinetic parameters were significantly different between the 2 housing environments. CLINICAL RELEVANCE Findings suggested that in dogs, housing environment (normal environment vs a cage in an unfamiliar environment) did not significantly affect oral absorption and, by extension, gastric emptying of acetaminophen.

Forecasting COVID-19 infection trends and new hospital admissions in England due to SARS-CoV-2 Variant of Concern Omicron

Objectives: On November 26, 2021, WHO designated the variant B.1.1.529 as a new SARS-CoV-2 variant of concern (VoC), named Omicron, originally identified in South Africa. Several mutations in Omicron indicate that it may have an impact on how it spreads, resistance to vaccination, or the severity of illness it causes. We used our previous modelling algorithms to forecast the spread of Omicron in England. Design: We followed EQUATOR TRIPOD guidance for multivariable prediction models. Setting: England. Participants: Not applicable. Interventions: Non-interventional, observational study with a predicted forecast of outcomes. Main outcome measures: Trends in daily COVID-19 cases with a 7-day moving average and of new hospital admissions. Methods: Modelling included a third-degree polynomial curve in existing epidemiological trends on the spread of Omicron and a new Gaussian curve to estimate a downward trend after a peak in England. Results: Up to February 15, 2022, we estimated a projection of 250,000 COVID-19 daily cases of Omicron spread in the worse scenario, and 170,000 in the best scenario. Omicron might represent a relative increase from the background daily rates of COVID-19 infection in England of mid December 2021 of 1.9 to 2.8-fold. With a 5-day lag-time, daily new hospital admissions would peak at around 5,063 on January 23, 2022 in the worse scenario. Conclusion: This warning of pandemic surge of COVID-19 due to Omicron is calling for further reinforcing in England and elsewhere of universal hygiene interventions (indoor ventilation, social distance, and face masks), and anticipating the need of new total or partial lockdowns in England.

Using NDII patterns to constrain semi-distributed rainfall-runoff models in tropical nested catchments

A parsimonious semi-distributed rainfall-runoff model has been developed for flow prediction. In distribution, attention is paid to both timing of runoff and heterogeneity of moisture storage capacities within sub-catchments. This model is based on the lumped FLEXL model structure, which has proven its value in a wide range of catchments. To test the value of distribution, the gauged Upper Ping catchment in Thailand has been divided into 32 sub-catchments, which can be grouped into 5 gauged sub-catchments where internal performance is evaluated. To test the effect of timing, firstly excess rainfall was calculated for each sub-catchment, using the model structure of FLEXL. The excess rainfall was then routed to its outlet using the lag time from storm to peak flow (TlagF) and the lag time of recharge from the root zone to the groundwater (TlagS), as a function of catchment size. Subsequently, the Muskingum equation was used to route sub-catchment runoff to the downstream sub-catchment, with the delay time parameter of the Muskingum equation being a function of channel length. Other model parameters of this semi-distributed FLEX-SD model were kept the same as in the calibrated FLEXL model of the entire Upper Ping basin, controlled by station P.1 located at the centre of Chiang Mai Province. The outcome of FLEX-SD was compared to: 1) observations at the internal stations; 2) the calibrated FLEXL model; and 3) the semi-distributed URBS model - another established semi-distributed rainfall-runoff model. FLEX-SD showed better or similar performance both during calibration and especially in validation. Subsequently, we tried to distribute the moisture storage capacity by constraining FLEX-SD on patterns of the NDII (normalized difference infrared index). The readily available NDII appears to be a good proxy for moisture stress in the root zone during dry periods. The maximum moisture holding capacity in the root zone is assumed to be a function of the maximum seasonal range of NDII values, and the annual average NDII values to construct 2 alternative models: FLEX-SD-NDIIMax-Min and FLEX-SD-NDIIAvg, respectively. The additional constraint on the moisture holding capacity by the NDII improved both model performance and the realism of the distribution. Distribution of Sumax using annual average NDII values was found to be well correlated with the percentage of evergreen forest in 31 sub-catchments. Spatial average NDII values were proved to be highly corresponded with the root zone soil moisture of the river basin, not only in the dry season but also in the water limited ecosystem. To check how well the model represents root zone soil moisture, the performance of the FLEX-SD-NDII model was compared to time series of the soil wetness index (SWI). The correlation between the root zone storage and the daily SWI appeared to be very good, even better than the correlation with the NDII, because NDII does not provide good estimates during wet periods. The SWI, which is partly model-based, was not used for calibration, but appeared to be an appropriate index for validation.

Predicting the growth of Listeria monocytogenes in cooked sliced deli turkey breast as function of clean label antimicrobial, pH, moisture and salt

The use of antimicrobials in formulations of ready-to-eat meat and poultry products has been identified as a major strategy to control Listeria monocytogenes . The USDA-FSIS recommends no more than 2-logs of Listeria outgrowth over the stated shelf life if antimicrobials are used as a control measure for a product with post-lethality environmental exposure. This study was designed to understand the efficacy of a clean label antimicrobial against the growth of L. monocytogenes as affected by the product attributes. A response surface method-central composite design was used to investigate the effects of product pH, moisture, salt content, and a commercial “clean-label” antimicrobial on the growth of L. monocytogenes in a model turkey deli meat formulation. Thirty treatment combinations of pH (6.3, 6.5, and 6.7), moisture (72, 75, and 78%), salt (1.0, 1.5, and 2.0%), and antimicrobial (0.75, 1.375, and 2.0%) with six replicated center points and eight design star points were evaluated. Treatments were surface inoculated with a 3 log 10 CFU/g target of a five-strain L. monocytogenes cocktail, vacuum packaged, and stored at 5°C for up to 16 weeks. Populations of L. monocytogenes were enumerated from triplicate samples every week until the stationary growth phase was reached. The enumeration data was fitted to a Baranyi and Roberts growth curve to calculate the lag time and maximum growth rate for each treatment. Linear least-squares regression of the lag-time and growth-rate against the full quadratic, including the second order interaction terms, design matrix was performed. Both lag time and maximum growth rate were significantly affected ( p <0.01) by the antimicrobial concentration and product pH. Product moisture and salt content affected ( p <0.05) lag phase and maximum growth rate, respectively. The availability of a validated growth model assists meat scientists and processors with faster product development and commercialization.

Pulsatile Delivery of Fexofenadine Hydrochloride Pulsincap by Box-Behnken Design

Objective: Fexofenadine hydrochloride is a selective peripheral H1-blocker, used for allergy symptoms, such as hay fever and urticaria. Allergic symptoms are aggressive during early morning hours, so a pulsatile delivery system with a lag time of 4-5 hours was formulated and optimized by Box-Behnken design. Materials and Methods: Pulsincap system using formaldehyde-treated capsules and hydrogel plug. Box-Behnken design was applied for optimization in which three independent variables, X1= Drug: polymer ratio, X2 = Polymer: polymer ratio (Ethylcellulose: HPMC E15) and X3 = Plug weight were selected. Three dependent variables R1 = Percent release of drug after 4 hours, R2 = percent release after 10 hours and R3 = Lag time were selected. Results: FTIR and DSC studies confirmed compatibility of drug and excipients. The empty formaldehyde-treated capsules were evaluated for physical appearance, solubility, capsule dimensions and formaldehyde content. Hydrogel plugs, powder blend and pulsincap formulations were evaluated for Physico-chemical parameters and all the parameters were within acceptable limits. Contour plots and Response surface plots indicated that as Drug: Polymer ratio (X1) and Plug weight (X3) increased, Lag time increased but% drug release decreased. As Polymer: Polymer ratio (X2) increased, the lag time was at a moderate level. Predicted vs actual responses showed the correlation of 0.786 for% release in 4hrs, 0.9744 for% release in 10hrs and 0.6281 for lag time. Optimized formulation G1 was suggested by design (with criteria 4.5-6hrs lag time, 10-20% release in 4hrs & 60-70% drug release within 10hrs). The optimised formulation was stable. Conclusion: Pulsincap system of Fexofenadine hydrochloride can be obtained by using retarding polymers like ethyl cellulose, HPMC E15 and formaldehyde cross-linked capsules.

Microbial Biogas Production From Pork Gelatine.

Dark fermentation of collagen (gelatine) results are shown in this research. The concentrations of applied gelatine were of VSS (volatile suspended solids) from 10 g VSS/L to 30 g VSS/L. The initial process pH was 5.5, depending on concentration reached pH values from 7.5 to 7.8 after 55 days. Although inoculum was heat-shocked in the case of 30 g VSS/L of collagen the process was hydrogenotrophic anaerobic digestion. In collagen concentration below 30 g VSS/L, hydrogen production was dominant only in the first 5 days of experiments. Then there also changed from dark fermentation into hydrogenotrophic methane production. In the case of optimal biogas production was due to accumulative production for a concentration of collagen 20 g VSS/L: 147.2 mL of hydrogen and 57.23 L of methane. In the case of optimal biogas production was due to accumulative production for a concentration of collagen 20 g VSS/L: 147.2 mL of hydrogen and 57.23 L of methane. The optimal hydrogen and methane yields were for concentration 10 g VSS/L (7.65 mL H2 /g VSS, and 3.49 L CH4/ g VSS). In 10 g VSS/L was also the lowest accumulated emission of hydrogen sulphide (10.3 mL of H2S), while the lowest yield was for 30 g VSS/L (0.44 mL H2S /g VSS). After a lag time, the hydrogen production and hydrogen sulphide grew with a specific ratio depending on concentration. Collagen, a protein with known amounts of sulphur allowed determining the origin of hydrogen sulphide in biogas. The hydrogen sulphide emission and sulphur added analysis proved that hydrogen sulphide origins in biogas from bacteria remains more than from substrate.

NanoGram Detection of Drilling Fluids Additives for Uncertainty Reduction in Surface Logging

Manual sampling rock cuttings off the shale shaker for lithology and petrophysical characterization is frequently performed during mud logging. Knowing the depth origin where the cuttings were generated is very important for correlating the cuttings to the petrophysical characterization of the formation. It is a challenge to accurately determine the depth origin of the cuttings, especially in horizontal sections and in coiled tubing drilling, where conventional logging while drilling is not accessible. Additionally, even in less challenging drilling conditions, many factors can contribute to an inaccurate assessment of the depth origin of the cuttings. Inaccuracies can be caused by variation of the annulus dimension used to determine the lag time (and thus the depth of the cuttings), by the shifting or scrambling of cuttings during their return trip back to the surface, and by the mislabelling of the cuttings during sampling. In this work, we report the synthesis and application of polystyrenic nanoparticles (NanoTags) in labeling cuttings for depth origin assessment. We have successfully tagged cuttings using two NanoTags during a drilling field test in a carbonate gas well and demonstrated nanogram detection capability of the tags via pyrolysis-GCMS using an internally developed workflow. The cuttings depth determined using our tags correlates well with the depth calculated by conventional mud logging techniques.