Accelerated evidence synthesis in orthopaedics—the roles of natural language processing, expert annotation and large language models

peer reviewedIn an era of electronical medical records, rapidly expanding publication rates of medical knowledge, and large-scale registries, orthopaedics is in a dire need of innovative approaches to facilitate the adoption of the latest knowledge in clinical practice. While machine learning (ML) has been heralded as one solution to many research tasks hampered by previous technological limitations [12], there is an increasing need to direct our attention towards subdomains of ML that are convenient for the extraction of meaningful clinical information stored in medical records. We believe natural language processing (NLP) to be one such domain of ML, with an immense future potential to catalyse rate-limiting steps in orthopaedic research

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Potencijalna upotreba izotopa važnih za okoliš u ispitivanju migracije onečišćujućih tvari

This article presents the use of natural abundance stable isotope (hydrogen, carbon, nitrogen, oxygen, chlorine) analysis data as a tool for providing important information about the origin of contaminants, the contribution of different sources to a multi-source plume, characterisation of their complex transport (rate and mechanisms) and for evaluating the success of contaminated site remediation. Isotopic signatures of contaminants are useful tracers of their sources, while isotopic fractionation can be used to quantitatively assess the progress of an environmental process such as biodegradation. This new isotopic approach is reliable and can offer more information than traditional techniques in pollutant migration studies, particularly after waste disposal. During biological degradation of any organic compound, molecules containing lighter isotopes are degraded, and the portion of heavier isotopes in the substrate is increased, identifying specific microbial roles in biogeochemical cycling. Since isotopic fractionation is proportional to degradation, depending on the type of contamination, a microbial degradation of 50 % to 99 % of the initial concentration can be quantified using isotope ratio measurements.Cilj ovog rada je da se prikaže korištenje podataka analize prirodne obilnosti stabilnih izotopa (vodika, ugljika, dušika, kisika i klora) kao alata za dobivanje važnih informacija o porijeklu onečišćujućih tvari, doprinosu različitih multikomponentnih onečišćivača, karakterizaciji njihova kompleksnog transporta (brzine i mehanizma) i praćenja uspjeha remedijacije onečišćenih mjesta. Izotopski sadržaji onečišćujućih tvari koriste se kao traseri za određivanje njihovih izvora, dok se izotopsko frakcioniranje može iskoristiti za kvantitativnu procjenu toka procesa kao što je biodegradacija. Takav nov izotopski pristup je pouzdan i nudi više informacija od tradicionalnih tehnika kontrole putovanja onečišćivala, napose nakon odlaganja opasnog otpada na zemljištu. Za vrijeme biodegradacije nekog organskog spoje molekule koje sadržavaju lake izotope lakše se degradiraju, a dio težih izotopa u supstratu se povećava, što upućuje na mikrobiološku ulogu u biokemijskom ciklusu. Kako je izotopsko frakcioniranje proporcionalno degradaciji zavisno od tipa onečišćenja, korištenjem podataka mjerenja izotopskih odnosa može se procijeniti mikrobiološka degradacija od 50 % do 99 % od početne koncentracije

Sightline jitter minimisation and shaping using nonlinear friction compensation

Friction-induced sightline jitter significantly degrades the image resolution and detection range of a stabilised optical system. Therefore, any controller that can reduce jitter levels in the stabilisation sub-system will have a significant impact on overall electro-optic system performance. This article presents the results of an investigation into several friction compensation models applied to the validated model of an in-service electro-optic turret. The turret test harness, system identification software and friction measurement techniques used in the validation procedure-experimental transfer function analysis-are presented. A worst-case approach was used in setting the sensor noise and base motion acceleration levels. This test data was then used to validate a mathematical model of the turret elevation axis for use in off-line design and tuning of six friction compensation controllers. Three types of friction compensator model were investigated; a linear Kalman filter, an extended Kalman filter with a static friction model and an extended Kalman filter using a dynamic friction model. Additionally, two controller architectures were used. All six controllers were shown to significantly reduce jitter levels overall, but a new controller architecture was shown to also further reduce image degradation due to smearing