Pre-drill pore pressure prediction is essential for safe and efficient drilling, and is a key element in the risk-reducing toolbox when designing a well. On the Norwegian Continental Shelf, pore pressure prediction commonly relies on traditional 1D offset well analysis, whereas velocity data from seismic surveys are often not considered. Our work with seismic interval velocities shows that the velocity field can provide an important basis for pressure prediction and enable the construction of regional 3D pressure cubes. This may increase the confidence in the pore pressure models and aid the pre-drill geohazard screening process. We demonstrate how a 3D velocity field can be converted to a 3D pore pressure cube using reported pressures in offset wells as calibration points. The method is applied to a regional dataset at the Halten Terrace in the Norwegian Sea; an area with a complex pattern of pore pressure anomalies which traditionally has been difficult to predict. The algorithm is searching for a velocity to pore pressure transform that best matches the reported pressures. The 3D velocity field is a proxy of rock velocity and is derived from seismic surveys, and is verified to checkshot velocities and sonic data in the offset wells.

The decline or drying up of groundwater sources near a tunnel route is damaging to groundwater users. Therefore, forecasting the impact of a tunnel on nearby groundwater sources is a challenging task in tunnel design. In this study, numerical and analytical approaches were applied to the Qomroud water conveyance tunnel (located in Lorestan province, Iran) to assess the impact of tunnelling on the nearby extraction water wells. Using simulation of groundwater-level fluctuation owing to tunnelling, the drawdown at the well locations was determined. From the drawdowns and using Dupuit's equation, the depletion of well flow rates after tunnelling was estimated. To evaluate the results, observed well flow rates before and after tunnelling were compared with the predicted flow rates. The observed and estimated water well flows (before and after tunnelling) showed a regression factor of 0.64, pointing to satisfactory results

Neuroendocrinelike transdifferentiation of prostate cancer adenocarcinomas correlates with serum levels of chromogranin A (CgA) and drives treatment resistance. The aim of this work was to evaluate whether CgA can serve as a response predictor for ¹⁷⁷Lu-prostate-specific membrane antigen 617 (PSMA) radioligand therapy (RLT) in comparison with the established tumor markers. Methods: One hundred consecutive patients with metastasized castration-resistant prostate cancer scheduled for PSMA RLT were evaluated for prostate-specific antigen (PSA), lactate dehydrogenase (LDH), and CgA at baseline and in follow-up of PSMA RLT. Tumor uptake of PSMA ligand, a known predictive marker for response, was assessed as a control variable. Results: From the 100 evaluated patients, 35 had partial remission, 16 stable disease, 15 mixed response, and 36 progression of disease. Tumor uptake above salivary gland uptake translated into partial remission, with an odds ratio (OR) of 60.265 (95% confidence interval [CI], 5.038–720.922). Elevated LDH implied a reduced chance for partial remission, with an OR of 0.094 (95% CI, 0.017–0.518), but increased the frequency of progressive disease (OR, 2.717; 95% CI, 1.391–5.304). All patients who achieved partial remission had a normal baseline LDH. Factor-2 elevation of CgA increased the risk for progression, with an OR of 3.089 (95% CI, 1.302–7.332). Baseline PSA had no prognostic value for response prediction. Conclusion: In our cohort, baseline PSA had no prognostic value for response prediction. LDH was the marker with the strongest prognostic value, and elevated LDH increased the risk for progression of disease under PSMA RLT. Elevated CgA demonstrated a moderate impact as a negative prognostic marker in general but was explicitly related to the presence of liver metastases. Well in line with the literature, sufficient tumor uptake is a prerequisite to achieve tumor response.

Monoclonal antibodies (mAbs) against programmed cell death 1 (PD-1), such as nivolumab and pembrolizumab, are associated with high response rates in patients with relapsed or refractory classic Hodgkin lymphoma (HL). To date, no prognostic factor for overall survival (OS) has been established with these agents in HL. We examined whether the first early response assessment evaluated using ¹⁸F-FDG PET/CT may be associated with OS in this setting. Methods: This retrospective study included 45 patients from 34 institutions. In a masked, centralized review, 3 independent radiologists classified PET/CT scans obtained at a median of 2.0 mo (interquartile range, 1.7–3.7 mo) after nivolumab initiation using existing criteria (i.e., 2014 Lugano classification and 2016 LYRIC). Patients were classified according to 4 possible response categories: complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD). Because the OS of patients with NMR and PMR was similar, they were grouped together. OS was estimated using the Kaplan–Meier method and compared between groups using log-rank testing. Results: Eleven patients (24%) died after a median follow-up of 21.2 mo. The classification was identical between Lugano and LYRIC because all 16 progression events classified as indeterminate response per LYRIC were confirmed on subsequent evaluations. Both Lugano and LYRIC classified patients as CMR in 13 cases (29%), PMD in 16 (36%), NMR in 4 (9%), and PMR in 12 (27%). The 2-y OS probability was significantly different in patients with PMD (0.53; 95% confidence interval [95%CI], 0.32–0.87), NMR or PMR (0.80; 95%CI, 0.63–1.00), and CMR (1.00; 95%CI, 1.00–1.00) in the overall population (P = 0.02, 45 patients), as well as according to a landmark analysis at 3 mo (P = 0.05, 32 patients). Conclusion: In relapsed or refractory HL patients treated with anti-PD-1 mAbs, the first early PET/CT assessment using either Lugano or LYRIC predicted OS and allowed early risk stratification, suggesting that PET/CT might be used to develop risk-adapted strategies.

OBJECTIVE

Type 2 diabetes is characterized by increased death rate. In order to tackle this dramatic event, it becomes essential to discover novel biomarkers capable of identifying high-risk patients to be exposed to more aggressive preventive and treatment strategies. hs-CRP and serum amyloid P component (SAP) are two acute-phase inflammation proteins, which interact physically and share structural and functional features. We investigated their combined role in associating with and improving prediction of mortality in type 2 diabetes.

PURPOSE

Although cesarean delivery is the most common surgical procedure in the United States, postoperative opioid prescribing varies greatly. We hypothesized that patient characteristics, procedural characteristics, or both would be associated with high vs low opioid use after discharge. This information could help individualize prescriptions.

Dramatically rising costs in drug development are in large part because of the high failure rates in clinical phase trials. The poor correlation of animal studies to human toxicity and efficacy have led many developers to question the value of requiring animal studies in determining which drugs should enter in-human trials. Part 1 of this 2-part series examined some of the data regarding the lack of concordance between animal toxicity studies and human trials, as well as some of the potential reasons behind it. This second part of the series focuses on some alternatives to animal trials (hereafter referred to as animal research) as well as current regulatory discussions and developments regarding such alternatives.

Purpose:

There are several agents in early clinical trials targeting components of the adenosine pathway including A2AR and CD73. The identification of cancers with a significant adenosine drive is critical to understand the potential for these molecules. However, it is challenging to measure tumor adenosine levels at scale, thus novel, clinically tractable biomarkers are needed.

In this retrospective study, whole-genome sequencing (WGS) data generated on an Ion Torrent platform was used to predict phenotypic drug resistance profiles for first- and second-line drugs among Swedish clinical Mycobacterium tuberculosis isolates from 2016 to 2018. The accuracy was ~99% for all first-line drugs and 100% for four second-line drugs. Our analysis supports the introduction of WGS into routine diagnostics, which might, at least in Sweden, replace phenotypic drug susceptibility testing in the future.

Addition of sodium bicarbonate (NaHCO₃) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO₃ responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ~75% and ~36% of isolates displayed the NaHCO₃ responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic β-lactam MICs in standard Mueller-Hinton broth (MHB) nor population analysis profiles were predictive of this phenotype. Several genotypic markers (clonal complex 8 [CC8]; agr I and spa t008) were associated with NaHCO₃ responsiveness for OXA.

The rising rates of antibiotic resistance increasingly compromise empirical treatment. Knowing the antibiotic susceptibility of a pathogen’s close genetic relative(s) may improve empirical antibiotic selection. Using genomic and phenotypic data for Escherichia coli isolates from three separate clinically derived databases, we evaluated multiple genomic methods and statistical models for predicting antibiotic susceptibility, focusing on potentially rapidly available information, such as lineage or genetic distance from archived isolates. We applied these methods to derive and validate the prediction of antibiotic susceptibility to common antibiotics. We evaluated 968 separate episodes of suspected and confirmed infection with Escherichia coli from three geographically and temporally separated databases in Ontario, Canada, from 2010 to 2018. Across all approaches, model performance (area under the curve [AUC]) ranges for predicting antibiotic susceptibility were the greatest for ciprofloxacin (AUC, 0.76 to 0.97) and the lowest for trimethoprim-sulfamethoxazole (AUC, 0.51 to 0.80). When a model predicted that an isolate was susceptible, the resulting (posttest) probabilities of susceptibility were sufficient to warrant empirical therapy for most antibiotics (mean, 92%). An approach combining multiple models could permit the use of narrower-spectrum oral agents in 2 out of every 3 patients while maintaining high treatment adequacy (~90%). Methods based on genetic relatedness to archived samples of E. coli could be used to predict antibiotic resistance and improve antibiotic selection.

Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1_LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC₅₀) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 x 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.

Patients with HPV16⁺ cervical cancer and high T-cell responses to an HPV16 vaccine survived longer.

A large international study found that the composition of the intestinal microbiome can predict clinical outcomes in patients undergoing allogenic hematopoietic-cell transplant (HCT) for blood cancers. The findings may help assess patients' transplantation-related mortality risk and aid in developing interventions to prevent or mitigate microbiome changes that affect HCT outcomes.

Background:

Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease.

BACKGROUND AND PURPOSE:

It is not known how radiomics using ultrasound images contribute to the detection of BRAF mutation. This study aimed to evaluate whether a radiomics study of gray-scale ultrasound can predict the presence or absence of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation in papillary thyroid cancer.

SUMMARY:

Use of mechanical thrombectomy for stroke has increased since the publication of trials describing outcome improvement when used in the anterior circulation. These results, however, cannot be directly translated to the posterior circulation. While a high NIHSS score has demonstrated an association with poor outcomes in posterior stroke, the NIHSS is weighted toward hemispheric disease, and complex scores potentially delay definitive imaging diagnosis. We performed a retrospective analysis to ascertain whether any rapidly obtainable demographic or clinical and imaging data have a correlation with patient outcome postthrombectomy. Seventy-three cases were audited between September 2010 and October 2017. Presenting with a Glasgow Coma Scale score of >13 meant that the odds of reaching the primary end point of functional independence (defined as a 90-day modified Rankin Scale score of 0–2) were 5.70 times greater; similarly, presenting with a posterior circulation ASPECTS of >9 resulted in the odds of reaching the primary end point being 4.03 times greater. Older age correlated to a lower odds of independence (0.97, p = .04).

BRITAIN'S summer holiday destinations will face some of the biggest economic hits of the coronavirus pandemic with fears of massive job losses in coastal communities, a study has claimed.

Bosch SoundSee combines deep learning with mobile microphone arrays to identify problems on the ISS before they happen

FIFA 20 Team Of The Season So Far continues this week, hopefully with the release of the La Liga FUT Squad. Here some predictions on who might be included, plus when they'll be announced.

FIFA 20 Team Of The Season So Far continues this week, hopefully with the additional release of the Portuguese Liga Nos FUT Squad. Here some predictions on who might be included, plus when they'll be announced.

FIFA 20 Team Of The Season So Far continues this week, hopefully with the release of the Bundesliga FUT Squad. Here some predictions on who might be included, plus when they'll be announced.

Neil Ferguson, whose modelling has informed the UK's coronavirus strategy, says that the need for intensive care beds will come close to, but not exceed, national capacity

With all the unknowns about covid-19, any numbers you hear about death tolls or how long restrictions will last should be taken not just with a pinch of salt but with a sack of it

Metabolites from urine or blood samples can be used to predict how much a baby will grow six months ahead of time, which could improve interventions for chronic malnutrition

The Simpsons has done it again, this time predicting the COVID-19 pandemic and murder hornets. Here are some other instances of The Simpsons predicting the future.

LIVERPOOL midfielder Georginio Wijnaldum will be pivotal for Jurgen Klopp at Manchester City..

Meat production this week is up about 3 percent compared with the previous week, according to market reports by SiriusXM’s Rural Radio. That’s still off by as much as a third from a year ago. The numbers are causing some retailers to ration fresh meat purchases or risk selling out their entire supplies. The beef,... Continue Reading

Thinning the Sierra Nevada forest by removing trees by hand or using heavy machinery is one of the few tools available to manage forests. However, finding the best way to thin forests by removing select trees to maximize the forest's benefits for water quantity, water quality, wildfire risk and wildlife habitat remains a challenge for resource managers.

A new global simulation model offers the first long-term look at how urbanization -- the growth of cities and towns -- will unfold in the coming decades. The research team projects the total amount of urban areas on Earth can grow anywhere from 1.8 to 5.9-fold by 2100, building approximately 618,000 square miles.

Ofsted chief inspector Amanda Spielman has suggested there could be a "mixed economy" of schooling as the coronavirus lockdown is eased.

The full regular-season schedule is out. The Chiefs open defense of their Super Bowl title vs. Houston.

New head writer Suzanne Heathcote's zombie-writing experience might come in handy. Where 'Killing Eve' had a vitality, it now feels tired to the point of lifelessness

Fans think The Simpsons predicted everything from Trump's presidency to coronavirus

'I thought at the time it was a work of fiction,' author says

'Ricky, you were way ahead of the curve!'

As Claire Danes puts Carrie Mathison to pasture, Jacob Stolworthy looks back at the series that justified its existence to the bitter end

It's the most accurate one yet

People have noted a certain timeliness in a clip from the 1993 episode 'Marge in Chains'

• Quarterback left New England for Tampa Bay in March
• Covid-19 means practices with teammates are missing

Eli Manning, the man who beat Tom Brady in two Super Bowls, thinks his old rival may find it tough adapting to life with his new team, the Tampa Bay Buccaneers.

Brady left the New England Patriots in March after two decades and six Super Bowl titles with the team. The Buccaneers are blessed with weapons, such as Mike Evans, Chris Godwin and Brady’s old teammate Rob Gronkowski on offense, but the Covid-19 lockdown is an added obstacle for the quarterback as he adjusts to a new playbook.

Related: Tom Brady will have more fun in Tampa, but will he win?

What does our crystal ball say the new year will bring for celebs? Sex tapes, terrible singing and off-the-cuff sofa jokes that ignite the far right. Sounds great!

There are two ways to spend New Year’s Eve, as best as I can tell: you either dirty the floor of a house party and spend the smallest of the small hours running desperately out of drinkable alcohol until you realise it’s 7am and the sun is up and you just watched yourself pour Pepsi Max into half a cup of Bailey’s until they both curdled into a sort of vomitty pâté; or you watched Jools at home with a blanket over your legs, in bed with your teeth brushed by 10 past 12. You get absolutely zero points for guessing which one of the two I saw the new year in with. My body is still shaking.

Fair to say, too, that celebrities have yet to emerge blinkingly into the new decade. In the Christmas lull, the famous go into one of two modes of hibernation: either posting a succession of matching-pyjama family selfies in million-pound mansions that are identically decorated with plush beige carpets and tasteful but anonymous tonal greys; or going on holiday somewhere unthinkably lush and posting: “How’s the weather back home!” while sizzling in a hammock over aquamarine Maldivian waters. What I am saying is that there is no news, all right, and we can’t spend 1,200 words having a go at Cats again, so we simply have to preview the year 2020 and have a stab at guessing what the world of fame has for us. Is it a cop-out? Or is it actually quite a decent effort for someone who still has “brandy” in his system and who many doctors would advise shouldn’t be sitting upright at this still-early stage in his hangover? Well exactly. Let’s get on with it.

Real Madrid may have missed out on signing Kylian Mbappe this summer due to the coronavirus.

West Ham manager David Moyes says he does not expect to have any more than three weeks to work with his players before the season resumes.

Damien Comolli, the former Liverpool and Tottenham director of football, believes the transfer window will be very different next time around due to the coronavirus pandemic.

Tanguy Ndombele's time at Tottenham could be over after just one year as Barcelona are reportedly ready to offer Samuel Umtiti and Nelson Semedo in exchange for the midfielder.

Former Barcelona midfielder Xavi Hernandez believes Lionel Messi can continue at the top level for five to seven years.

Football fans will finally have some live action to watch on Friday, when the South Korean K-League returns from its coronavirus shutdown.

Welcome to Standard Sport's LIVE coverage of the K-League openers between Jeonbuk Hyundai Motors and the Suwon Samsung Bluewings

Game fishers are predicting one of the best seasons in 30 years, but are wary about publicising their big catches online due to growing criticism about the sport.

Yes, rain is on the forecast for parts of the country, although it won't be drought-breaking. But as the rainclouds gather on the horizon the question we are all asking is: "Where is it going to fall?".