Learning skillful medium-range global weather forecasting.

Global medium-range weather forecasting is critical to decision-making across many social and economic domains. Traditional numerical weather prediction uses increased compute resources to improve forecast accuracy but does not directly use historical weather data to improve the underlying model. Here, we introduce GraphCast, a machine learning-based method trained directly from reanalysis data.

Results of 'two-in-one' single-stage revision total knee arthroplasty for infection with associated bone loss : prospective five-year follow up.

Aims: Periprosthetic joint infection (PJI) occurs in approximately 1% to 2% of total knee arthroplasties (TKA) presenting multiple challenges, such as difficulty in diagnosis, technical complexity, and financial costs. Two-stage exchange is the gold standard for treating PJI but emerging evidence suggests 'two-in-one' single-stage revision as an alternative, delivering comparable outcomes, reduced morbidity, and cost-effectiveness. This study investigates five-year results of modified single-stage revision for treatment of PJI following TKA with bone loss.

The ability to kneel before and after total knee arthroplasty : the role of the pattern of osteoarthritis and the position of the femoral component.

Aims: The aims of this study were to investigate the ability to kneel after total knee arthroplasty (TKA) without patellar resurfacing, and its effect on patient-reported outcome measures (PROMs). Secondary aims included identifying which kneeling positions were most important to patients, and the influence of radiological parameters on the ability to kneel before and after TKA.

Methods: This prospective longitudinal study involved 209 patients who underwent single radius cruciate-retaining TKA without patellar resurfacing.

Radiographic severity, extent and pattern of cartilage loss are not associated with patient reported outcomes before or after total knee arthroplasty in end-stage knee osteoarthritis.

Background: The aim of this study was to determine if radiographic severity, extent or pattern of knee osteoarthritis was associated with pain and function before total knee arthroplasty (TKA) or improvement therein one year after TKA.

Methods: A prospective study of 259 patients undergoing unilateral TKA for Kellgren-Lawrence (KL) grade ≥ 3 knee osteoarthritis was conducted: mean age 69.8 ± 9.

Patellar cartilage loss does not affect early outcomes of total knee arthroplasty performed without patella resurfacing.

Background: The aim of this study was to compare the outcomes and cost economics of TKA without patella resurfacing in patients with and without patellar cartilage loss.

Methods: Prospective case control study of 209 consecutive patients undergoing TKA without patella resurfacing. Patella cartilage status was documented intra-operatively: 108 patients had patella cartilage loss (mean age 70 ± 9.

Population mobility and adult orthopaedic trauma services during the COVID-19 pandemic: fragility fracture provision remains a priority.

Aims: This study aims to define the epidemiology of trauma presenting to a single centre providing all orthopaedic trauma care for a population of ∼ 900,000 over the first 40 days of the COVID-19 pandemic compared to that presenting over the same period one year earlier. The secondary aim was to compare this with population mobility data obtained from Google.

Methods: A cross-sectional study of consecutive adult (> 13 years) patients with musculoskeletal trauma referred as either in-patients or out-patients over a 40-day period beginning on 5 March 2020, the date of the first reported UK COVID-19 death, was performed.

Patterns of cartilage loss and anterior cruciate ligament status in end-stage osteoarthritis of the knee.

Aims: This study aims to determine the proportion of patients with end-stage knee osteoarthritis (OA) possibly suitable for partial (PKA) or combined partial knee arthroplasty (CPKA) according to patterns of full-thickness cartilage loss and anterior cruciate ligament (ACL) status.

Methods: A cross-sectional analysis of 300 consecutive patients (mean age 69 years (SD 9.5, 44 to 91), mean body mass index (BMI) 30.

Correlations between radiological classification systems and confirmed cartilage loss in severe knee osteoarthritis.

Aims: Although knee osteoarthritis (OA) is diagnosed and monitored radiologically, actual full-thickness cartilage loss (FTCL) has rarely been correlated with radiological classification. This study aims to analyze which classification system correlates best with FTCL and to assess their reliability.

Methods: A prospective study of 300 consecutive patients undergoing unilateral total knee arthroplasty (TKA) for OA (mean age 69 years (44 to 91; standard deviation (SD) 9.

Results of Using a "2-in-1" Single-Stage Revision Total Knee Arthroplasty for Infection with Associated Bone Loss: Prospective 2-Year Follow-Up.

Prosthetic joint infections provide a complex challenge for management, owing to their often difficult diagnoses, need for multiple surgeries, and increased technical and financial requirements. The '2 in 1' single-stage approaches have been recently advocated in the field of arthroplasty on account of their reduction in risks, costs, and complications. The aim of our study was to investigate the outcomes of this variant of single-stage revision, which is used in the setting of infection following primary total knee replacement (TKR) and associated bone loss.

Comparison of technical success and complications of percutaneous transhepatic cholangiography and biliary drainage between patients with and without transplanted liver.

Objective: The purpose of this study is to compare technical success and complications of percutaneous transhepatic cholangiography (PTC) and percutaneous transhepatic biliary drainage (PTBD) between patients with and without transplanted liver.

Materials And Methods: Between 2007 and 2011, 89 PTCs, including 34 PTBDs, in 87 patients with transplanted liver were attempted, and 131 PTCs, including 118 PTBDs, in 126 patients without transplanted liver were attempted. Technical success, diameters of the bile ducts, fluoroscopy time, and complications were statistically compared between the two groups.

Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675).

Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SAR development, which led to the discovery of potent allosteric GK activators 9a and 21a, is described.

Development of reliable aqueous solubility models and their application in druglike analysis.

In this work, two reliable aqueous solubility models, ASMS (aqueous solubility based on molecular surface) and ASMS-LOGP (aqueous solubility based on molecular surface using ClogP as a descriptor), were constructed by using atom type classified solvent accessible surface areas and several molecular descriptors for a diverse data set of 1708 molecules. For ASMS (without using ClogP as a descriptor), the leave-one-out q(2) and root-mean-square error (RMSE) were 0.872 and 0.

Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of different treatment protocols.

Purpose: To prospectively assess patient response (after 12 months) to magnetic resonance (MR) imaging-guided focused ultrasound surgery in treatment of uterine leiomyomas by using two treatment protocols.

Materials And Methods: This prospective clinical trial was approved by institutional review boards and was HIPAA compliant. After giving informed consent, patients with symptomatic leiomyomas were consecutively enrolled and treated at one of five U.

Genetic algorithm-optimized QSPR models for bioavailability, protein binding, and urinary excretion.

In this work, a genetic algorithm (GA) was applied to build up a set of QSPR (quantitative structure-property relationship) models for human absolute oral bioavailability, plasma protein binding, and urinary excretion using the counts of molecular fragments as descriptors. For a pharmacokinetic property, the consensus score of a set of models (20 or 30) was found to improve the correlation coefficient and reduce the standard error significantly. Key fragments that may boost or reduce pharmacokinetic properties were also identified.

Atypical polypoid adenomyoma mimicking cervical adenocarcinoma.

Atypical polypoid adenomyoma (APA) of the uterus is a rare, benign lesion. Histologically, it is composed of a glandular and squamous cell proliferation with architectural complexity and cytologic atypia of glands, and a hypercellular smooth muscle stroma. APA is difficult to distinguish from well-differentiated adenocarcinoma of the uterus.

Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.

Sitaxsentan (1) (Wu et al. J. Med.

Development of cell adhesion molecule antagonists as therapeutics for asthma and COPD.

Airway inflammation is a hallmark of respiratory diseases such as asthma and chronic obstructive pulmonary disease. Cell adhesion molecules play critical roles in the recruitment and migration of cells to sites of inflammation. Not surprisingly, these receptors have garnered the attention of the pharmaceutical industry as targets for the development of drugs to treat inflammatory and autoimmune diseases.

Functional magnetic resonance cholangiography (fMRC) of the gallbladder and biliary tree with contrast-enhanced magnetic resonance cholangiography.

Purpose: To determine the diagnostic performance of functional magnetic resonance cholangiography (fMRC) for the evaluation of anatomic and functional biliary disorders.

Materials And Methods: At 1.5 T, 39 MR examinations with conventional MRC and mangafodipir trisodium-enhanced fMRC were retrospectively reviewed by three observers who recorded anatomic (duct dilation, stricture, filling defects) and functional (cholecystitis, obstruction) abnormalities in three modes: MRC alone, fMRC alone, and MRC and fMRC images together (combined-MRC).

Hepatic MR imaging with ferumoxides: multicenter study of safety and effectiveness of direct injection protocol.

Purpose: To compare the safety and effectiveness of an undiluted direct injection of ferumoxides with those of a diluted slow infusion of ferumoxides during 30 minutes in patients with known liver lesions or in those suspected of having them.

Materials And Methods: Two hundred thirty-three patients at 16 institutions were randomized to receive either an undiluted direct injection of 0.56 mg of iron per kilogram of body weight of ferumoxides administered during 2 minutes (2 mL/min) or a diluted slow infusion administered during 30 minutes.

Recently discovered sulfonamide-, acyl sulfonamide- and carboxylic acid-based endothelin antagonists.

Endothelins (ET-1, 2 and 3) are 21-residue peptides with two disulfide bridges and a highly conserved carboxy terminal. ET-1, the most significant isoform, is a potent vasoconstrictor and mitogen that exerts its biological effects through binding to its two G protein-coupled receptors: ET(A) and ET(B). ET(A) receptors are expressed on vascular smooth muscle cells and mediate vasoconstrictive and proliferative responses to ET-1.

Nonpeptide endothelin antagonists in clinical development.

Endothelins (ET-1, ET-2 and ET-3) are 21-amino-acid peptides with two disulfide bonds that belong to the sarafotoxin family. ET-1, ET-2 and ET-3 are produced endogenously from preproendothelin to give big endothelins, which are cleaved by endothelin-converting enzyme (ECE) to yield the active protein. Endothelin has been shown to play important physiological and pathological roles by interacting with its G-protein-coupled receptors.

Suspected early or mild chronic pancreatitis: enhancement patterns on gadolinium chelate dynamic MRI. Magnetic resonance imaging.

Purpose: To assess whether measuring the pattern of pancreatic enhancement on gadolinium chelate dynamic magnetic resonance imaging (MRI) is helpful for diagnosis of suspected early or mild chronic pancreatitis.

Materials And Methods: In this retrospective study, 24 patients with suspected early or mild chronic pancreatitis, classified by imaging criteria of equivocal chronic pancreatitis (ultrasound, computed tomography [CT] or ERCP) grading, had dynamic MRI that included unenhanced, arterial dominant, early venous, and late venous phases of contrast enhancement. Twenty patients without pancreatic diseases also had the dynamic sequence as a control group.

Cirrhosis: modified caudate-right lobe ratio.

Purpose: To determine whether a modified caudate-right lobe ratio (C/RL) with use of the right portal vein to set the lateral boundary (C/RL-r) is more accurate for diagnosing cirrhosis and evaluating its clinical severity than is the previously described C/RL with use of the main portal vein to set the lateral boundary (C/RL-m).

Materials And Methods: Two hundred thirty-six patients (121 with pathologically proved cirrhosis and 115 without history of chronic hepatic diseases) underwent magnetic resonance (MR) imaging. Two independent observers measured C/RL-r and compared it with C/RL-m.