Reactive oxygen and nitrogen species have been implicated in many biological processes and diseases, including immune responses, cardiovascular dysfunction, neurodegeneration, and cancer. These chemical species are short-lived in biological settings, and detecting them in these conditions and diseases requires the use of molecular probes that form stable, easily detectable, products. The chemical mechanisms and limitations of many of the currently used probes are not well-understood, hampering their effective applications. Boronates have emerged as a class of probes for the detection of nucleophilic two-electron oxidants. Here, we report the results of an oxygen-18–labeling MS study to identify the origin of oxygen atoms in the oxidation products of phenylboronate targeted to mitochondria. We demonstrate that boronate oxidation by hydrogen peroxide, peroxymonocarbonate, hypochlorite, or peroxynitrite involves the incorporation of oxygen atoms from these oxidants. We therefore conclude that boronates can be used as probes to track isotopically labeled oxidants. This suggests that the detection of specific products formed from these redox probes could enable precise identification of oxidants formed in biological systems. We discuss the implications of these results for understanding the mechanism of conversion of the boronate-based redox probes to oxidant-specific products.

South Africa is a mineral-rich country with a diverse geology and a long history of mining. The rich history of mining activities includes the extraction of coal from the Ecca Group Sediments of the Karoo Supergroup (250 Ma), gold and uranium from the Witwatersrand Supergroup (2900 Ma), as well as platinum, uranium, tin and lead from the layered Bushveld Igneous Complex (BIC) (2150 Ma). The extraction of gold, copper, tin, lead and rare earth minerals also took place in the Archean rocks of Swazium age (3500–3000 Ma). The historical mining records have either not been accurately recorded or have been lost over time. This has resulted in significant geohazard risk during infrastructure development, especially in and around historical mining towns, such as Johannesburg and Ermelo. These geohazard risks require careful appraisal and quantification prior to any infrastructure design or construction.

This case study aims to set out the development aspects of the Multi-Faceted Geophysical Modelling Systems approach, which was used by the South African National Roads Agency SOC Ltd (SANRAL) during an investigation of undermined ground for the historical coal-mining town of Ermelo in South Africa. The N11/N2 ring road was planned to go around Ermelo to ensure mobility between major routes, whilst still maintaining town access.

The systems approach used a combination of airborne geophysics (Versatile Time Domain Electromagnetic System (VTEM^TM) and magnetics), generally used in mining exploration, land-based and borehole geophysics, borehole water testing, and ground-truthing. The approach was continuous and iterative, building on the data at hand and reducing unnecessary investigations while eliminating the possibility of anomalies being missed, as in the case of conventional discrete drilling. The investigation ensured that 100% of the route was comprehensively investigated with a high confidence in the geological and geophysical data, and concomitant mitigation of infrastructure risk.

The Multi-Faceted Geophysical Modelling Systems approach was successfully used to identify a previously unknown 1 x 1 m mining stope cavity at 90 m depth and a 3 x 5 m access tunnel at 24 m depth in a timely and cost-effective manner. Seven reverse-circulation percussion boreholes confirmed the structural integrity of these underground cavities, as well as the structural geology along the centreline. Based on the great success achieved in identifying shallow anomalies, this Multi-Faceted Geophysical Modelling Systems approach is now being considered for field trails on the dolomitic formations and the Wild Coast greenfields road project where there are large historical slumps and many fault lines.

Thematic collection: This article is part of the Ground-related risk to transportation infrastructure collection available at https://www.lyellcollection.org/cc/Ground-related-risk-to-transportation-infrastructure

A logistic regression model and a bivariate statistical analysis were used in this paper to evaluate the groundwater recharge susceptibility. The approach is based on the assessment of the relationship involving groundwater recharge and parameters that influence this hydrological process. Surface parameters and aquifer-related parameters were evaluated as thematic map layers using ArcGIS. Then, a weighted-rating method was adopted to categorize each parameter's map. To assess the role of each parameter in the aquifer recharge, a logistic regression model and a bivariate statistical analysis were applied to the Guenniche phreatic aquifer (Tunisia). Models are explored to establish a map showing the aquifer recharge susceptibility. The code Modflow was used to simulate the consequence of the recharge. The recharge amount was introduced in the model and was tested to verify the recharge effect on the hydraulic head for the two models. The obtained results reveal that the recharge as mapped in the bivariate statistical model has a minor impact on the hydraulic head. Results of the logistic regression model are more significant as the hydraulic head is widely affected. This model provides good results in mapping the spatial distribution of the aquifer recharge susceptibility.

The human immune system relies on highly complex and diverse transcripts and the proteins they encode. These include transcripts encoding human leukocyte antigen (HLA) receptors as well as B cell and T cell receptors (BCR and TCR). Determining which alleles an individual possesses for each HLA gene (high-resolution HLA typing) is essential to establish donor–recipient compatibility in organ and bone marrow transplantations. In turn, the repertoires of millions of unique BCR and TCR transcripts in each individual carry a vast amount of health-relevant information. Both short-read RNA-seq-based HLA typing and BCR/TCR repertoire sequencing (AIRR-seq) currently rely on our incomplete knowledge of the genetic diversity at HLA and BCR/TCR loci. Here, we generated over 10,000,000 full-length cDNA sequences at a median accuracy of 97.9% using our nanopore sequencing-based Rolling Circle Amplification to Concatemeric Consensus (R2C2) protocol. We used this data set to (1) show that deep and accurate full-length cDNA sequencing can be used to provide isoform-level transcriptome analysis for more than 9000 loci, (2) generate accurate sequences of HLA alleles, and (3) extract detailed AIRR data for the analysis of the adaptive immune system. The HLA and AIRR analysis approaches we introduce here are untargeted and therefore do not require prior knowledge of the composition or genetic diversity of HLA and BCR/TCR loci.

The first Biograph Vision PET/CT system (Siemens Healthineers) was installed at the University Medical Center Groningen. Improved performance of this system could allow for a reduction in activity administration or scan duration. This study evaluated the effects of reduced scan duration in oncologic ¹⁸F-FDG PET imaging on quantitative and subjective imaging parameters and its influence on clinical image interpretation. Methods: Patients referred for a clinical PET/CT scan were enrolled in this study, received a weight-based ¹⁸F-FDG injected activity, and underwent list-mode PET acquisition at 180 s per bed position (s/bp). Acquired PET data were reconstructed using the vendor-recommended clinical reconstruction protocol (hereafter referred to as "clinical"), using the clinical protocol with additional 2-mm gaussian filtering (hereafter referred to as "clinical+G2"), and—in conformance with European Association of Nuclear Medicine Research Ltd. (EARL) specifications—using different scan durations per bed position (180, 120, 60, 30, and 10 s). Reconstructed images were quantitatively assessed for comparison of SUVs and noise. In addition, clinically reconstructed images were qualitatively evaluated by 3 nuclear medicine physicians. Results: In total, 30 oncologic patients (22 men, 8 women; age: 48–88 y [range], 67 ± 9.6 y [mean ± SD]) received a single weight-based (3 MBq/kg) ¹⁸F-FDG injected activity (weight: 45–123 kg [range], 81 ± 15 kg [mean ± SD]; activity: 135–380 MBq [range], 241 ± 47.3 MBq [mean ± SD]). Significant differences in lesion SUV_max were found between the 180-s/bp images and the 30- and 10-s/bp images reconstructed using the clinical protocols, whereas no differences were found in lesion SUV_peak. EARL-compliant images did not show differences in lesion SUV_max or SUV_peak between scan durations. Quantitative parameters showed minimal deviation (~5%) in the 60-s/bp images. Therefore, further subjective image quality assessment was conducted using the 60-s/bp images. Qualitative assessment revealed the influence of personal preference on physicians’ willingness to adopt the 60-s/bp images in clinical practice. Although quantitative PET parameters differed minimally, an increase in noise was observed. Conclusion: With the Biograph Vision PET/CT system for oncologic ¹⁸F-FDG imaging, scan duration or activity administration could be reduced by a factor of 3 or more with the use of the clinical+G2 or the EARL-compliant reconstruction protocol.

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.

Negative circumferential resection margins (CRM) are the cornerstone for the curative treatment of locally advanced rectal cancer (LARC). However, in up to 18.6% of patients, tumor-positive resection margins are detected on histopathology. In this proof-of-concept study, we investigated the feasibility of optical molecular imaging as a tool for evaluating the CRM directly after surgical resection to improve tumor-negative CRM rates. Methods: LARC patients treated with neoadjuvant chemoradiotherapy received an intravenous bolus injection of 4.5 mg of bevacizumab-800CW, a fluorescent tracer targeting vascular endothelial growth factor A, 2–3 d before surgery (ClinicalTrials.gov identifier: NCT01972373). First, for evaluation of the CRM status, back-table fluorescence-guided imaging (FGI) of the fresh surgical resection specimens (n = 8) was performed. These results were correlated with histopathology results. Second, for determination of the sensitivity and specificity of bevacizumab-800CW for tumor detection, a mean fluorescence intensity cutoff value was determined from the formalin-fixed tissue slices (n = 42; 17 patients). Local bevacizumab-800CW accumulation was evaluated by fluorescence microscopy. Results: Back-table FGI correctly identified a tumor-positive CRM by high fluorescence intensities in 1 of 2 patients (50%) with a tumor-positive CRM. For the other patient, low fluorescence intensities were shown, although (sub)millimeter tumor deposits were present less than 1 mm from the CRM. FGI correctly identified 5 of 6 tumor-negative CRM (83%). The 1 patient with false-positive findings had a marginal negative CRM of only 1.4 mm. Receiver operating characteristic curve analysis of the fluorescence intensities of formalin-fixed tissue slices yielded an optimal mean fluorescence intensity cutoff value for tumor detection of 5,775 (sensitivity of 96.19% and specificity of 80.39%). Bevacizumab-800CW enabled a clear differentiation between tumor and normal tissue up to a microscopic level, with a tumor-to-background ratio of 4.7 ± 2.5 (mean ± SD). Conclusion: In this proof-of-concept study, we showed the potential of back-table FGI for evaluating the CRM status in LARC patients. Optimization of this technique with adaptation of standard operating procedures could change perioperative decision making with regard to extending resections or applying intraoperative radiation therapy in the case of positive CRM.

A vial-capping process for lyophilization stopper configurations was previously quantified using residual seal force (RSF). A correlation between RSF and container closure integrity (CCI) was established, and component positional offsets were identified to be the primary source of variability in RSF measurements.

To gain insight into the effects of stopper geometry on CCI, serum stoppers with the same rubber formulation were investigated in this study. Unlike lyophilization stoppers that passed CCI (per helium leak testing) even with RSF of 0 N owing to their excellent valve seal, serum stoppers consistently failed CCI when RSF was <15.8 N. When the plug was removed, both types of stoppers exhibited a comparable critical lower RSF limit (19–20 N), below which CCI could not be maintained. When CCI was retested at later time points (up to 6 mo), some previously failed vials passed CCI, suggesting that CCI improvement might be related to rubber relaxation (viscous flow), which can fill minor imperfections on the vial finish.

To confirm component positional offsets are the primary sources of RSF variability, a novel quantification tool—micro-computed tomography (micro-CT)—was used in this study. Micro-CT provided images for quantification of positional offsets of the cap and stopper that directly correlated with RSF fluctuations. Serum stoppers and lyophilization stoppers are comparable in RSF variations, although lyophilization stoppers are more robust in CCI. The use of micro-CT provides a nondestructive and innovative tool in quantitatively analyzing component features of capped vials that would otherwise be difficult to investigate.

Background:

Unnecessary antibiotic use in the community in Canada is not well defined. Our objective was to quantify unnecessary antibiotic prescribing in a Canadian primary care setting.

Methods:

We performed a descriptive analysis in Ontario from April 2011 to March 2016 using the Electronic Medical Records Primary Care database linked to other health administrative data sets at ICES. We determined antibiotic prescribing rates (per 100 patient–physician encounters) for 23 common conditions and estimated rates of unnecessary prescribing using predefined expected prescribing rates, both stratified by condition and patient age group.

Results:

The study included 341 physicians, 204 313 patients and 499 570 encounters. The rate of unnecessary antibiotic prescribing for included conditions was 15.4% overall and was 17.6% for those less than 2 years of age, 18.6% for those aged 2–18, 14.5% for those aged 19–64 and 13.0% for those aged 65 or more. The highest unnecessary prescribing rates were observed for acute bronchitis (52.6%), acute sinusitis (48.4%) and acute otitis media (39.3%). The common cold, acute bronchitis, acute sinusitis and miscellaneous nonbacterial infections were responsible for 80% of the unnecessary antibiotic prescriptions. Of all antibiotics prescribed, 12.0% were for conditions for which they are never indicated, and 12.3% for conditions for which they are rarely indicated. In children, 25% of antibiotics were for conditions for which they are never indicated (e.g., common cold).

Interpretation:

Antibiotics were prescribed unnecessarily for 15.4% of included encounters in a Canadian primary care setting. Almost one-quarter of antibiotics were prescribed for conditions for which they are rarely or never indicated. These findings should guide safe reductions in the use of antibiotics for the common cold, bronchitis and sinusitis.

With increased interest in lipoprotein(a) (Lp[a]) concentration as a target for risk reduction and growing clinical evidence of its impact on cardiovascular disease (CVD) risk, rigorous analytical performance specifications (APS) and accuracy targets for Lp(a) are required. We investigated the biological variation (BV) of Lp(a), and 2 other major biomarkers of CVD, apolipoprotein A-I (apoA-I) and apolipoprotein B-100 (apoB), in the European Biological Variation Study population.Serum samples were drawn from 91 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate on a Roche Cobas 8000 c702. Outlier, homogeneity, and trend analysis were performed, followed by CV-ANOVA to determine BV estimates and their 95% CIs. These estimates were used to calculate APS and reference change values. For Lp(a), BV estimates were determined on normalized concentration quintiles.Within-subject BV estimates were significantly different between sexes for Lp(a) and between women aged <50 and >50 years for apoA-I and apoB. Lp(a) APS was constant across concentration quintiles and, overall, lower than APS based on currently published data, whereas results were similar for apoA-I and apoB.Using a fully Biological Variation Data Critical Appraisal Checklist (BIVAC)–compliant protocol, our study data confirm BV estimates of Lp(a) listed in the European Federation of Clinical Chemistry and Laboratory Medicine database and reinforce concerns expressed in recent articles regarding the suitability of older APS recommendations for Lp(a) measurements. Given the heterogeneity of Lp(a), more BIVAC-compliant studies on large numbers of individuals of different ethnic groups would be desirable.

This work established a new murine venous thromboembolism (VTE) model. This model has multiple novel features representing clinical VTE that include the following: 1) deep venous thrombosis (DVT) was formed and extended in the long axis of femoral/saphenous vein; 2) thrombus was formed in a venous valve pocket; 3) deligation of suture-induced spontaneous pulmonary emboli of fibrin-rich DVT; and 4) cardiac motion-free femoral/saphenous vein allowed high-resolution intravital microscopic imaging of fibrin-rich DVT. This new model requires only commercially available epifluorescence microscopy. Therefore, this model has significant potential for better understanding of VTE pathophysiology.

Purpose:

Using standard-of-care CT images obtained from patients with a diagnosis of non–small cell lung cancer (NSCLC), we defined radiomics signatures predicting the sensitivity of tumors to nivolumab, docetaxel, and gefitinib.

Experimental Design:

Data were collected prospectively and analyzed retrospectively across multicenter clinical trials [nivolumab, n = 92, CheckMate017 (NCT01642004), CheckMate063 (NCT01721759); docetaxel, n = 50, CheckMate017; gefitinib, n = 46, (NCT00588445)]. Patients were randomized to training or validation cohorts using either a 4:1 ratio (nivolumab: 72T:20V) or a 2:1 ratio (docetaxel: 32T:18V; gefitinib: 31T:15V) to ensure an adequate sample size in the validation set. Radiomics signatures were derived from quantitative analysis of early tumor changes from baseline to first on-treatment assessment. For each patient, 1,160 radiomics features were extracted from the largest measurable lung lesion. Tumors were classified as treatment sensitive or insensitive; reference standard was median progression-free survival (NCT01642004, NCT01721759) or surgery (NCT00588445). Machine learning was implemented to select up to four features to develop a radiomics signature in the training datasets and applied to each patient in the validation datasets to classify treatment sensitivity.

Results:

The radiomics signatures predicted treatment sensitivity in the validation dataset of each study group with AUC (95 confidence interval): nivolumab, 0.77 (0.55–1.00); docetaxel, 0.67 (0.37–0.96); and gefitinib, 0.82 (0.53–0.97). Using serial radiographic measurements, the magnitude of exponential increase in signature features deciphering tumor volume, invasion of tumor boundaries, or tumor spatial heterogeneity was associated with shorter overall survival.

Conclusions:

Radiomics signatures predicted tumor sensitivity to treatment in patients with NSCLC, offering an approach that could enhance clinical decision-making to continue systemic therapies and forecast overall survival.

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.

We investigated dose-fractionated polymyxin B (PB) on acute kidney injury (AKI). PB at 12 mg of drug/kg of body weight per day (once, twice, and thrice daily) was administered in rats over 72 h. The thrice-daily group demonstrated the highest KIM-1 increase (P = 0.018) versus that of the controls (P = 0.99) and histopathological damage (P = 0.013). A three-compartment model best described the data (bias, 0.129 mg/liter; imprecision, 0.729 mg²/liter²; R², 0.652,). Area under the concentration-time curve at 24 h (AUC₂₄) values were similar (P = 0.87). The thrice-daily dosing scheme resulted in the most PB-associated AKI in a rat model.

Background:

We assessed the ability to supplement existing epidemiologic/etiologic studies with data on treatment and clinical outcomes by linking to publicly available cancer registry and administrative databases.

Methods:

Medical records were retrieved and abstracted for cases enrolled in a Los Angeles County case–control study of non-Hodgkin lymphoma (NHL). Cases were linked to the Los Angeles County cancer registry (CSP), the California state hospitalization discharge database (OSHPD), and the SEER-Medicare database. We assessed sensitivity, specificity, and positive predictive value (PPV) of cancer treatment in linked databases, compared with medical record abstraction.

Results:

We successfully retrieved medical records for 918 of 1,004 participating NHL cases and abstracted treatment for 698. We linked 59% of cases (96% of cases >65 years old) to SEER-Medicare and 96% to OSHPD. Chemotherapy was the most common treatment and best captured, with the highest sensitivity in SEER-Medicare (80%) and CSP (74%); combining all three data sources together increased sensitivity (92%), at reduced specificity (56%). Sensitivity for radiotherapy was moderate: 77% with aggregated data. Sensitivity of BMT was low in the CSP (42%), but high for the administrative databases, especially OSHPD (98%). Sensitivity for surgery reached 83% when considering all three datasets in aggregate, but PPV was 60%. In general, sensitivity and PPV for chronic lymphocytic leukemia/small lymphocytic lymphoma were low.

Conclusions:

Chemotherapy was accurately captured by all data sources. Hospitalization data yielded the highest performance values for BMTs. Performance measures for radiotherapy and surgery were moderate.

Impact:

Various administrative databases can supplement epidemiologic studies, depending on treatment type and NHL subtype of interest.

The Klenow fragment, which retains the template-dependent deoxynucleotide polymerizing activity and the 3' -> 5' exonuclease of the holo-enzyme but lacks its powerful 5' -> 3' exonuclease activity, is used to fill recessed 3' termini of dsDNA. In this protocol, fragments suitable as templates for the end-filling reaction are produced by digestion of DNA with an appropriate restriction enzyme. The Klenow enzyme is then used to catalyze the attachment of dNTPs to the recessed 3'-hydroxyl groups.

Adeno-associated virus (AAV) recombinants are currently the vector of choice for many gene therapy applications. As experimental therapies progress to clinical trials, the need to characterize recombinant adeno-associated viruses (rAAVs) accurately and reproducibly increases. Accurate determination of rAAV infectious titer is important for determining the activity of each vector lot and for ensuring lot-to-lot consistency. The following protocol developed in our laboratory uses a 96-well TCID₅₀ format and quantitative polymerase chain reaction (qPCR) detection for the determination of rAAV infectious titer.

This protocol is used to determine the concentration of DNase-resistant vector genomes (i.e., packaged in the capsid) in purified recombinant adeno-associated virus (rAAV) preparations. The protocol begins with treatment of the vector stock with DNase I to eliminate unencapsidated AAV DNA or contaminating plasmid DNA. This is followed by a heat treatment to heat-inactivate DNase I, to disrupt the viral capsid, and to release the packaged vector genomes for quantification by real-time polymerase chain reaction (PCR) using a set of standards (linearized plasmid used for vector production) containing known copy numbers. To accomplish high-throughput titration, the primer and probe sets used in real-time PCR are usually designed to target common elements present in most rAAV genomes, such as promoters and poly(A) signals. This strategy significantly reduces the number of PCRs, controls, and turnaround time. Several important controls should be included in the assay as follows: The first two controls should have a known copy number of the rAAV genome plasmid treated or not treated with DNase I. This control tests the effectiveness of DNase treatment. To control for potential cross-contamination between samples during the preparation process, a blank control containing nuclease-free water only should be processed and tested in parallel. A validation vector sample with a known titer should be included in every assay to monitor interassay variability. Finally, for the PCR run, a no-template control (NTC) is included to indicate cross-contamination during PCR setup.

Although ample evidence indicates that immune cell homeostasis is an important prognostic outcome determinant in patients with cancer, few studies have examined whether it also determines cancer risk among initially healthy individuals. We performed a case–cohort study including incident cases of breast (n = 207), colorectal (n = 111), lung (n = 70), and prostate (n = 201) cancer as well as a subcohort (n = 465) within the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort. Relative counts of neutrophils, monocytes, and lymphocyte sublineages were measured by qRT-PCR. HRs and 95% confidence intervals were used to measure the associations between relative counts of immune cell and cancer risks. When relative counts of immune cell types were taken individually, a significant positive association was observed between relative counts of FOXP3+ regulatory T cells (Tregs) and lung cancer risk, and significant inverse associations were observed between relative CD8+ counts and risks of lung and breast cancer (overall and ER+ subtype). Multivariable models with mutual adjustments across immune markers showed further significant positive associations between higher relative FOXP3+ T-cell counts and increased risks of colorectal and breast cancer (overall and ER− subtype). No associations were found between immune cell composition and prostate cancer risk. These results affirm the relevance of elevated FOXP3+ Tregs and lower levels of cytotoxic (CD8+) T cells as risk factors for tumor development.Significance:This epidemiologic study supports a role for both regulatory and cytotoxic T cells in determining cancer risk among healthy individuals.See related commentary by Song and Tworoger, p. 1801

An annual report released by the Ministry of Construction (MoC) at a press conference on Monday showed housing prices in the two mảo cities Hanoi and Ho Chi Minh (HCMC) rose slightly in the third quarter (Q3) of this year.

The constantly increasing number of new real estate projects which have been implemented in the Mekong Delta region has led to the rising land price and strong fluctuation in the local property market.

So you’ve got an idea of the Hanoi district you might want to live in from our last post. Now onto the types of housing available and what you can expect to pay.

To ensure that you can afford for your living expenditures, you should not spend more than 30-40% of income on housing.

Cám ơn anh chị đã ghé thăm tin đăng của em. Em bên PKD của Easy Housing chi nhánh Masteri Thảo Điền. Bên em hiện đang có rất nhiều sản phẩm giá tốt, rẻ hơn đến 300 triệu so với giá thị trường trước mùa dịch. Dành cho anh chị chưa biết đến Masteri Thảo Điền, em sẽ giới thiệu một c...

QR codes, tracking apps and drones at toll booths are just some of the tech tools China is deploying to monitor the spread of the new coronavirus

The hypothetical Planet 9 has been bandied about for several years, first mentioned in 2014, but researchers have yet to find it. Now, a well-known theoretical physicist believes we could find the mysterious object using "laser-launched spacecraft."

Miley Cyrus doesn't get a reply from all the celebrities she messages.

The oil industry saw its opening and moved with breathtaking speed to take advantage of this moment

I’m going to tell you the single worst story I’ve heard in these past few horrid months, a story that combines naked greed, political influence peddling, a willingness to endanger innocent human beings, utter blindness to one of the greatest calamities in human history and a complete disregard for the next crisis aiming for our planet. I’m going to try to stay calm enough to tell it properly, but I confess it’s hard.

The background: a decade ago, beginning with indigenous activists in Canada and farmers and ranchers in the American west and midwest, opposition began to something called the Keystone XL pipeline, designed to carry filthy tar sands oil from the Canadian province of Alberta to the Gulf of Mexico. It quickly became a flashpoint for the fast-growing climate movement, especially after Nasa scientist James Hansen explained that draining those tar sands deposits would be “game over” for the climate system. And so thousands went to jail and millions rallied and eventually Barack Obama bent to that pressure and blocked the pipeline. Donald Trump, days after taking office, reversed that decision, but the pipeline has never been built, both because its builder, TC Energy, has had trouble arranging the financing and permits, and because 30,000 people have trained to do nonviolent civil disobedience to block construction. It’s been widely assumed that, should a Democrat win the White House in November, the project would finally be gone for good.

Continue reading...

Hydrogen is a possible next generation energy solution, and it can be produced from sunlight and water using photocatalysts. A research group has now developed a strategy that greatly increases the amount of hydrogen produced using hematite photocatalysts. In addition to boosting the high efficiency of what is thought to be the world's highest performing photoanode, this strategy will be applied to artificial photosynthesis and solar water-splitting technologies via university-industry collaborations.

Read our live coronavirus updates HERE Coronavirus: The symptoms

Follow our live coronavirus updates HERE Coronavirus: The symptoms

A man was tasered and held by police after he was found brandishing a knife on a south-east London housing block.

In today's Diary: how Whitehall's cats are coping with coronavirus / Russell Crowe sideswipes Oliver Reed / Angela Scanlon on the glory of cheese / Michael Fabricant vows to wear pink shorts

Residents in a small English village have put up scarecrows in their gardens to show support for key workers during the coronavirus pandemic.

Elon Musk caused shares in his company Tesla to drop more than 11 per cent after tweeting that the price is "too high".

On Monday, officials in Los Angeles County released preliminary results of a study that suggest roughly 4.1% of the county's adult population has already had the coronavirus, which translates to between 221,000 and 442,000 people, factoring in adjustments for statistical margin of error.That's a much higher number than confirmed case counts indicate. (As of early Tuesday, the county had 13,816 cases.)"We haven't known the true extent of COVID-19 infections in our community because we have only tested people with symptoms and the availability of tests has been limited," Neeraj Sood, a professor of public policy at the University of Southern California and lead investigator on the study, said in a statement.Dr. Barbara Ferrer, LA County's public health director, said in a statement that the early results pointed to the possibility that many people may have been unknowingly infected.The study relies on rapid antibody tests, which have faced concerns about accuracy.And as The Mercury News reported, a Stanford study that also showed higher rates of infection in Santa Clara County drew criticism, although that was largely from statisticians over the study's methodology.Still, experts have emphasized that more studies will help develop a clearer picture of the virus's true prevalence.In any case, officials say it's crucial to continue to adhere to public health orders for many reasons, including that if more people are infected but asymptomatic, they could unknowingly spread the virus.______A change to the USNS Mercy's assignmentOn Monday, my New York Times colleague John Ismay and I spoke with leaders aboard the Navy hospital ship Mercy. Here's our dispatch about how their assignment has changed:In the weeks since the Mercy arrived at the Port of Los Angeles from San Diego, the hospital ship's mission has been clear: Serve as a crucial relief valve for patients who have not been infected with the coronavirus as hospitals fill up with patients sick with COVID-19.In recent days, the work has shifted, but that underlying goal has remained the same, the commanding officer of the ship's medical facility told us."FEMA, after having made an assessment of the situation and the local needs, has changed our assignment," said Capt. John Rotruck, the medical treatment team's commanding officer.The Mercy has sent 40 medical staff members -- two family practice doctors, 16 nurses and 20 corpsmen, including two respiratory technicians -- to help care for patients who do not have COVID-19 at a state-run skilled nursing facility in Orange County."We're essentially augmenting their staff," Rotruck said, as the anticipated surge in COVID-19 hospitalizations has, for now, been held at bay.The capacity onboard will decrease to 250 beds from 1,000, in large part as a result of that staffing shift -- although officials emphasized that leaves more than enough space at the rate the Mercy has been taking in patients.At the same time, leaders aboard the Mercy said that most of the military crew is moving off the ship to stay at nearby hotels to make it possible for crew members to keep their distance from one another as they work, eat and sleep.Sailors will be bused from their hotels to work their shifts aboard the ship.The move, which will decrease the number of crew members staying aboard the ship to roughly 140 from more than 800, came as the number of crew members who may have been exposed inched upward.By Monday, Rotruck said that nine crew members had tested positive for the coronavirus and that about 130 people were in quarantine because they had come into what federal officials define as close contact with at least one of those nine. All of those in quarantine tested negative.All nine who have COVID-19 were outpatients as of Monday -- meaning their cases were not severe enough to warrant being hospitalized -- and their conditions are being closely monitored.Rotruck said that moving crew members off the Mercy was unusual but not unprecedented.During a previous mission, for instance, some medical staff members flew to Vietnam to provide medical care to patients on the Mercy, although they did not sleep on the ship.However, Rotruck added, "We have not done it to this scale," with the vast majority of the ship's crew members living ashore.A spokesman said Friday that the crew aboard the Navy hospital ship Comfort, which is docked in New York City, recently moved most of its crew to hotels ashore as well.Rotruck said that the Mercy was ready to care for coronavirus-negative seniors living in nursing homes, as the governor has previously announced, but none had been transferred yet.Such nursing home patients may be moved to the Mercy for care through the typical intake process, if, for example, a facility needed to free up space to care for COVID-19 patients.As of Monday evening, the ship had taken in 65 patients total since it docked in San Pedro, and its crew had performed 22 surgeries. There were 13 patients still being treated onboard, meaning that 52 had been discharged.This article originally appeared in The New York Times.(C) 2020 The New York Times Company

The remote working stakes have just gone up a notch

Covid-19 could be 'antidote to complacency' among those on the fence about vaccines, scientists say

Canada Mortgage and Housing Corp. says construction of multi-unit housing projects remained strong in some provinces last month despite the fight against the COVID-19 pandemic.

NHS hospitals are asking for basic items such as toothbrushes and sanitary products

The tech giants shared details Monday about the tools they’ve been developing to help governments and public health authorities trace the spread of the coronavirus.

A Winnipeg woman who was a subject of misogynistic comments in a private group chat involving NHL players said she will continue her campaign of encouraging body acceptance.

Modern dating techniques are providing new time frames for indigenous settlements in Northeast North America, free from the Eurocentric bias that previously led to incorrect assumptions.

The 'Joe Lycett's Got Your Back' presenter legally changed his name in March

Lyft users must self-certify that they are following CDC guidelines related to COVID-19.

Covid protection, but make it fashion

Covid protection, but make it fashion

We're already dreaming about our 2021 holidays