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Abstract Fluctuating climate, heat, and drought are expected to considerably impact bread wheat (Triticum aestivum) quality in the coming years and, as wheat is an essential food element worldwide, this will have significant implications for future food security and the global economy. This leads to an urgent need for developing wheat varieties with stable yield and gluten quality. In this study, we investigated the effect of heat and drought, compared to a cool climate, on gluten proteins in 294 spring wheat genotypes grown in 2017 and 2018 in Sweden. Gluten protein parameters were studied by size exclusion high‐performance liquid chromatography (SE‐HPLC) and grain morphology by X‐ray tomography. The prolonged heat and drought led to: (i) increased gluten polymerization and the formation of large polymers, as defined by the percentage of unextractable polymers in total polymers (%UPP) and the percentage of large unextractable polymers in total large polymers (%LUPP); and (ii) increase in large monomers, as defined by the percentage of large unextractable monomers in the total large monomers (%LUMP) and the ratio of monomers versus polymers (Mon/Pol) in the flour. The cooler climate also led to an increase in total protein concentration and accumulation of the monomeric proteins and total SDS‐extractable proteins (TOTE). No difference in the total amount of SDS‐unextractable proteins (TOTU) was found between the studied climates. Due to the heat and drought stress, the grain yield decreased in most of the genotypes, while the grain microstructure varied only to a minor extent. The wheat genotypes identified in the study that provide good yields and stable gluten properties in both prolonged heat–drought and cool environments are strong candidates to contribute to a secure, self‐sufficient future wheat supply in the face of an evolving climate in Sweden and in similar climates worldwide.

Abstract Background The overuse of medical tests leads to higher costs, wasting of resources, and the potential for overdiagnosis of disease. This study was designed to determine whether the patients of family doctors who order more routine medical tests are diagnosed with more cancers. Method A retrospective population‐based cross‐sectional study using administrative health care data in Ontario Canada. We investigated the ordering of 23 routine laboratories and imaging tests 2008‐20012 by 6849 Ontario family physicians on their 4.9 million rostered adult patients. We compared physicians’ test utilization and calculated case‐mix adjusted observed to expected (O:E) utilization ratios to categorize physicians as Typical, Higher or Lower testers. Age‐sex standardized rates (cases/10 000 patient years) and Rate Ratios were determined for cancers of the thyroid, prostate, breast, lymphoma, kidney, melanoma, uterus, ovary, lung, esophagus, and pancreas for each tester group. Results There was wide variation in the use of the 23 tests by Ontario physicians. 26% and 24% of physicians were deemed Higher Testers for laboratory and imaging tests, while 41% and 38% were Typical Testers. The patients of higher test users were diagnosed with more cancers of thyroid (laboratory [RR 1.61, 95% CI 1.39‐1.87] and imaging [RR 2.08, 95% CI 0.88‐2.30]) and prostate (laboratory [RR 1.10, 95% CI 1.03‐1.18] and imaging [RR 1.05, 95% CI 1.00‐1.10]). Conclusion There is a wide variation in the ordering of routine and common medical tests among Ontario family doctors. The patients of higher testers were diagnosed with more thyroid and prostate cancers.

Abstract The Worldwide Alzheimer's Disease Neuroimaging Initiative (WW‐ADNI) is a collaborative effort to investigate imaging and biofluid markers that can inform Alzheimer's disease treatment trials. It is a public‐private partnership that spans North America, Argentina, Australia, Canada, China, Japan, Korea, Mexico, and Taiwan. In 2004, ADNI researchers began a naturalistic, longitudinal study that continues today around the globe. Through several successive phases (ADNI‐1, ADNI‐GO, ADNI‐2, and ADNI‐3), the study has fueled amyloid and tau phenotyping and refined neuroimaging methodologies. WW‐ADNI researchers have successfully standardized analyses and openly share data without embargo, providing a rich data set for other investigators. On August 26, 2020, the Alzheimer's Association convened WW‐ADNI researchers who shared updates from ADNI‐3 and their vision for ADNI‐4.

Regulatory agencies currently recommend itraconazole (ITZ) as a strong cytochrome P450 3A (CYP3A) inhibitor for clinical drug–drug interaction (DDI) studies. This work by an International Consortium for Innovation and Quality in Pharmaceutical Development working group (WG) is to develop and verify a mechanistic ITZ physiologically‐based pharmacokinetic model and provide recommendations for optimal DDI study design based on model simulations. To support model development and verification, in vitro and clinical PK data for ITZ and its metabolites were collected from WG member companies. The model predictions of ITZ DDIs with seven different CYP3A substrates were within the guest criteria for 92% of area under the concentration‐time curve ratios and 95% of maximum plasma concentration ratios, thus verifying the model for DDI predictions. The verified model was used to simulate various clinical DDI study scenarios considering formulation, duration of dosing, dose regimen, and food status to recommend the optimal design for maximal inhibitory effect by ITZ.

The drug–drug interaction profile of atorvastatin confirms that disposition is determined by cytochrome P450 (CYP) 3A4 and organic anion transporting polypeptides (OATPs). Drugs that affect gastric emptying, including dulaglutide, also affect atorvastatin pharmacokinetics (PK). Atorvastatin is a carboxylic acid that exists in equilibrium with a lactone form in vivo. The purpose of this work was to assess gastric acid–mediated lactone equilibration of atorvastatin and incorporate this into a physiologically‐based PK (PBPK) model to describe atorvastatin acid, lactone, and their major metabolites. In vitro acid‐to‐lactone conversion was assessed in simulated gastric fluid and included in the model. The PBPK model was verified with in vivo data including CYP3A4 and OATP inhibition studies. Altering the gastric acid–lactone equilibrium reproduced the change in atorvastatin PK observed with dulaglutide. The model emphasizes the need to include gastric acid–lactone conversion and all major atorvastatin‐related species for the prediction of atorvastatin PK.