Introduction Artificial intelligence (AI) and machine learning (ML) are rapidly evolving fields in various sectors, including healthcare. This article reviews AI’s present applications in healthcare, including its benefits, limitations and future scope. Sources of data A review of the English literature was conducted with search terms ‘AI’ or ‘ML’ or ‘deep learning’ and ‘healthcare’ or ‘medicine’ using PubMED and Google Scholar from 2000–2021. Areas of agreement AI could transform physician workflow and patient care through its applications, from assisting physicians and replacing administrative tasks to augmenting medical knowledge. Areas of controversy From challenges training ML systems to unclear accountability, AI’s implementation is difficult and incremental at best. Physicians also lack understanding of what AI implementation could represent. Growing points AI can ultimately prove beneficial in healthcare, but requires meticulous governance similar to the governance of physician conduct. Areas timely for developing research Regulatory guidelines are needed on how to safely implement and assess AI technology, alongside further research into the specific capabilities and limitations of its medical use.

HighlightsTranscriptional feedback is insufficient to account for circadian rhythm generation.Post-translational regulators of daily cellular clocks are conserved among eukaryotes.Eukaryotic circadian timekeeping may result from divergent evolution.

SummaryCircadian (approximately daily) rhythms are a pervasive property of mammalian cells, tissues, and behaviour, ensuring physiological and metabolic adaptation to solar time. Models of daily cellular timekeeping revolve around transcriptional feedback repression, whereby CLOCK and BMAL1 activate the expression of ‘clock proteins’ PERIOD (PER) and CRYPTOCHROME (CRY), which in turn repress CLOCK/BMAL1 activity. CRY proteins are thus considered essential negative regulators of the oscillation; a function supported by behavioural arrhythmicity of CRY-deficient mice when kept under constant conditions. Challenging this interpretation, however, we find evidence for persistent circadian rhythms in mouse behaviour and cellular PER2 levels when CRY is absent. CRY-less oscillations are variable in their expression and have a shorter period than wild type controls. Importantly, we find classic circadian hallmarks such as temperature compensation and determination of period by casein kinase 1δ/ε activity to be maintained. In the absence of CRY-mediated transcriptional feedback repression and rhythmic Per2 transcription, PER2 protein rhythms are sustained for several cycles, accompanied by circadian variation in protein stability. We suggest that, whereas circadian transcriptional feedback imparts robustness and functionality onto biological clocks, the core timekeeping mechanism is post-translational. Our findings suggest that PER proteins normally act as signalling hubs that transduce timing information to the nucleus, imparting daily rhythms upon the activity of transcriptional effectors.Highlights➢PER/CRY-mediated negative feedback is dispensable for mammalian circadian timekeeping➢Circadian variation in PER2 levels persists in the absence of rhythmic Per2 transcription➢CK1 and GSK3 are plausible mechanistic components of a ‘cytoscillator’ mechanism➢CRY-mediated feedback repression imparts robustness to biological timekeepingIn briefCircadian turnover of mammalian clock protein PERIOD2 persists in the absence of canonical transcriptional feedback repression and rhythmic clock gene activity, demanding a re-evaluation of cellular clock function and evolution.

efuroxime sodium (1 mg/0.1 mL) appears to be effective in preventing endophthalmitis. 1,2 Kaiser Permanente surgeons began injecting intracameral cefuroxime in 2007, with resulting declining rates of infection. 3,4 Cefuroxime is available in Europe as Aprokam, a manufactured product for intracameral injection. In the United States, no intracameral antibiotic preparation is approved to prevent endophthalmitis, thus creating a need for compounding for each surgical case. Reports have shown a long-term deleterious effect on the retina and cornea of injecting cefuroxime sodium at concentrations greater than 50 mg, 5,6 while no adverse effect has been observed at 3 mg. 7 We describe transient macular edema from injection of 9 mg of cefuroxime sodium. MethodsFollowing Kaiser Permanente Institutional Review Board approval, we reviewed medical records of 11 patients (13 eyes) who underwent cataract surgery by a single surgeon (D.C.W.) on a single day. In this article, exposed eye refers to an eye that underwent surgery and was injected with cefuroxime sodium at a dose of 9 mg/ 0.1 mL on that day. Reduced vision refers to Snellen visual acuity of 20/70 or worse on postoperative day 1 following uncomplicated clear-cornea cataract surgery. Data were collected and analyzed between June 2014 and January 2015. Informed consent was not required owing to the retrospective nature of the study.All patients were prescribed topical prednisolone acetate, 1%, diclofenac, 0.1%, and ofloxacin, 0.3%, 4 times daily in the eye undergoing surgery beginning 3 days prior to surgery. Two of the 11 patients underwent bilateral same-day surgery. Ordinarily, 750 mg of cefuroxime sodium injectable powder is reconstituted with 7.5 mL of preservative-free normal saline (sodium chloride, 0.9%). Three milliliters (300 mg) of the resulting solution is then injected into an empty 30-mL sterile interior vial. To this, 27 mL of preservative-free normal saline is added, resulting in a final cefuroxime sodium concentration of 1 mg/0.1 mL. 8 At each procedure's conclusion, 0.1 mL of compounded cefuroxime sodium solution was injected through the paracentesis. However, on this day, the final concentration was 9 mg/0.1 mL. Results Postoperative Day 1On the first postoperative day, 6 of 13 eyes (46%; 95% CI, 19%-75%) had reduced vision with uncorrected distance visual acu-IMPORTANCE Intracameral injection of cefuroxime sodium (1 mg/0.1 mL) has been reported to reduce the risk of endophthalmitis following cataract surgery. In the United States it must be compounded, which is subject to dilution error. We describe a series of 13 eyes that received intracameral injection of cefuroxime sodium, 9 mg/0.1 mL, intraoperatively.OBSERVATIONS On postoperative day 1, 6 of 13 eyes (46%; 95% CI, 19%-75%) had visual acuity of 20/70 or worse and macular edema. Spectral-domain optical coherence tomography of 2 eyes revealed central subfield thicknesses of 909 and 873 μm. On postoperative day 4, the mean (SD) central subfield thickness was 309 (78) μm in the 6 eyes with diagnosed...

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