Ray tracing intraocular lens calculation performance improved by AI-powered postoperative lens position prediction.

AIMS: To assess whether incorporating a machine learning (ML) method for accurate prediction of postoperative anterior chamber depth (ACD) improves cataract surgery refraction prediction performance of a commonly used ray tracing power calculation suite (OKULIX). METHODS AND ANALYSIS: A dataset of 4357 eyes of 4357 patients with cataract was gathered at the Kellogg Eye Center, University of Michigan. A previously developed machine learning (ML)-based method was used to predict the postoperative ACD based on preoperative biometry measured with the Lenstar LS900 optical biometer. Refraction predictions were computed with standard OKULIX postoperative ACD predictions and ML-based predictions of postoperative ACD. The performance of the ray tracing approach with and without ML-based ACD prediction was evaluated using mean absolute error (MAE) and median absolute error (MedAE) in refraction prediction as metrics. RESULTS: Replacing the standard OKULIX postoperative ACD with the ML-predicted ACD resulted in statistically significant reductions in both MAE (1.7% after zeroing mean error) and MedAE (2.1% after zeroing mean error). ML-predicted ACD substantially improved performance in eyes with short and long axial lengths (p<0.01). CONCLUSIONS: Using an ML-powered postoperative ACD prediction method improves the prediction accuracy of the OKULIX ray tracing suite by a clinically small but statistically significant amount, with the greatest effect seen in long eyes.

Delay in the induction of labour process: a retrospective cohort study and computer simulation of maternity unit workload.

OBJECTIVES: Delay in the induction of labour (IOL) process is associated with poor patient experience and adverse perinatal outcome. Our objective was to identify factors associated with delay in the IOL process and develop interventions to reduce delay. DESIGN AND SETTINGS: We performed a retrospective cohort study of maternity unit workload in a large UK district general hospital. Electronic hospital records were used to quantify delay in the IOL process and linear regression analysis was performed to assess significant associations between delay and potential causative factors. A novel computer maternity unit simulation model, MUMSIM (Maternity Unit Management SIMulation), was developed using real-world data and interventions were tested to identify those associated with a reduction in delay. PARTICIPANTS: All women giving birth at Stoke Mandeville Hospital, Buckinghamshire National Health Service (NHS) Trust in 2018 (n=4932). PRIMARY OUTCOME MEASURE: Delay in the IOL process of more than 12 hours. RESULTS: The retrospective analysis of real-world maternity unit workload showed 30% of women had IOL and of these, 33% were delayed >12 hours with 20% delayed >24 hours, 10% delayed >48 hours and 1.3% delayed >72 hours. Delay was significantly associated with the total number of labouring women (p=0.008) and the number of booked IOL (p=0.009) but not emergency IOL, spontaneously labouring women or staffing shortfall. The MUMSIM computer simulation predicted that changing from slow release 24-hour prostaglandin to 6-hour prostaglandin for primiparous women would reduce delay by 4% (p<0.0001) and that additional staffing interventions could significantly reduce delay up to 17.9% (p<0.0001). CONCLUSIONS: Planned obstetric workload of booked IOL is associated with delay rather than the unpredictable workload of women in spontaneous labour or emergency IOL. We present a novel maternity unit computer simulation model, MUMSIM, which allows prediction of the impact of interventions to reduce delay.

Gender differences in refraction prediction error of five formulas for cataract surgery.

OBJECTIVES: To evaluate gender differences in optical biometry measurements and lens power calculations. METHODS: Eight thousand four hundred thirty-one eyes of five thousand five hundred nineteen patients who underwent cataract surgery at University of Michigan's Kellogg Eye Center were included in this retrospective study. Data including age, gender, optical biometry, postoperative refraction, implanted intraocular lens (IOL) power, and IOL formula refraction predictions were gathered and/or calculated utilizing the Sight Outcomes Research Collaborative (SOURCE) database and analyzed. RESULTS: There was a statistical difference between every optical biometry measure between genders. Despite lens constant optimization, mean signed prediction errors (SPEs) of modern IOL formulas differed significantly between genders, with predictions skewed more hyperopic for males and myopic for females for all 5 of the modern IOL formulas tested. Optimization of lens constants by gender significantly decreased prediction error for 2 of the 5 modern IOL formulas tested. CONCLUSIONS: Gender was found to be an independent predictor of refraction prediction error for all 5 formulas studied. Optimization of lens constants by gender can decrease refraction prediction error for certain modern IOL formulas.

Epithelial Plaque Formation Secondary to Recombinant Human Nerve Growth Factor.

PURPOSE: To report a case of corneal epithelial plaque formation associated with recombinant human nerve growth factor (cenegermin 0.002%; Oxervate, Dompe[Combining Acute Accent] US Inc., Boston, MA), an as-yet unreported adverse event. METHODS: A case report and review of literature. RESULTS: A 45-year-old woman presented with a nonhealing 3.25- × 4.25-mm corneal epithelial defect secondary to multifactorial neurotrophic keratitis in the right eye. The epithelial defect was resistant to maximal medical therapy, and so cenegermin 0.002% was initiated, resulting in resolution of the corneal epithelial defect. After 6.5 weeks of treatment, she developed an unusual corneal epithelial plaque, decreased visual acuity, and eye pain. Cenegermin was ceased, after which the lesion resolved, visual acuity improved, and eye pain resolved. CONCLUSIONS: Cenegermin 0.002% has emerged as a promising treatment for neurotrophic keratitis. Reported adverse events with this agent have been minor and typically not vision threatening. Here, we describe corneal epithelial plaque formation as a visually significant adverse event that resolved with cessation of cenegermin 0.002%. Although the underlying mechanism is unknown, clinicians should be alerted to the possibility of epithelial plaque formation in patients being treated with recombinant human nerve growth factor for neurotrophic keratitis.

Single-cell RNA-seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63.

Cancers acquire resistance to systemic treatment with platinum-based chemotherapy (eg, cisplatin [CDDP]) as a result of a dynamic intratumoral heterogeneity (ITH) and clonal repopulation. However, little is known about the influence of chemotherapy on ITH at the single-cell level. Here, mapping the transcriptome of cancers treated with CDDP by scRNA-seq, we uncovered a novel gene, COX7B, associated with platinum-resistance, and surrogate marker, CD63. Knockdown of COX7B in cancer cells decreased the sensitivity of CDDP whereas overexpression recovered the sensitivity of CDDP. Low COX7B levels correlated with higher mortality rates in patients with various types of cancer and were significantly associated with poor response to chemotherapy in urinary bladder cancer. Tumor samples from patients, who underwent CDDP therapy, showed decreased COX7B protein levels after the treatment. Analyzing scRNA-seq data from platinum-naïve cancer cells demonstrated a low-COX7B subclone that could be sorted out from bulk cancer cells by assaying CD63. This low-COX7B subclone behaved as cells with acquired platinum-resistance when challenged to CDDP. Our results offer a new transcriptome landscape of platinum-resistance that provides valuable insights into chemosensitivity and drug resistance in cancers, and we identify a novel platinum resistance gene, COX7B, and a surrogate marker, CD63.

ELECTIVIST: a novel system to improve elective caesarean section booking.

Elective caesarean sections (ELCS) vary widely in surgical complexity and are routinely performed between 39 and 40 weeks of pregnancy. Unselected ELCS lists may create clinical risk due to inappropriately complex case mixes and over-running theatre time, impacting on emergency care. Despite evidence that ELCS list over-run is a widespread concern for many units, there is a paucity of literature regarding effective ELCS booking systems. We designed a novel ELCS risk scoring system, ELECTIVIST, comprising a risk assessment by the booking clinician and allocation of a complexity score to each case from 1 to 6. The maximum risk score for any one patient was 6, with a maximum total score on any one ELCS list of 6 and a maximum of three cases per list. We performed a retrospective analysis of all ELCS performed in our unit in 2016 using existing booking information and theatre data to assess existing case mix complexity and theatre over-run. This showed that 36% of ELCS lists were overbooked with inappropriately complex case mix and 21% of lists over-ran with 6% impacting on emergency obstetric theatres. Assessment of the impact of ELECTIVIST on ELCS capacity prior to implementation showed that no additional capacity was required to accommodate existing complexity. At 6 months following implementation, theatre over-run was reduced to 10% and over-run impacting on emergency theatre to 1%. The requirement for extra ELCS lists to accommodate capacity reduced by 66%. ELECTIVIST is a novel system that improves ELCS booking using existing capacity and reduces theatre list over-run. It is transferable, cost neutral and could be widely applied in obstetric units.

Population Genomics in Wild Tomatoes-The Interplay of Divergence and Admixture.

Hybridization between closely related plant species is widespread, but the outcomes of hybridization are not fully understood. This study investigates phylogenetic relationships and the history of hybridization in the wild tomato clade (Solanum sect. Lycopersicon). We sequenced RNA from individuals of 38 different populations and, by combining this with published data, build a comprehensive genomic data set for the entire clade. The data indicate that many taxa are not monophyletic and many individuals are admixed due to repeated hybridization. The most polymorphic species, Solanum peruvianum, has two genetic and geographical subpopulations, while its sister species, Solanum chilense, has distinct coastal populations and reduced heterozygosity indicating a recent expansion south following speciation from S. peruvianum circa 1.25 Ma. Discontinuous populations west of 72° are currently described as S. chilense, but are genetically intermediate between S. chilense and S. peruvianum. Based upon molecular, morphological, and crossing data, we test the hypothesis that these discontinuous "S. chilense" populations are an example of recombinational speciation. Recombinational speciation is rarely reported, and we discuss the difficulties in identifying it and differentiating between alternative demographic scenarios. This discovery presents a new opportunity to understand the genomic outcomes of hybridization in plants.

A cross-sectional comparison of three guidelines for intrapartum cardiotocography.

OBJECTIVE: To compare the cardiotocography classification systems outlined by the International Federation of Gynecology and Obstetrics (FIGO) in 2015 and the UK National Institute for Health and Care Excellence (NICE) in 2007 and 2014. METHODS: A cross-sectional observational study of cardiotocography practices at a UK hospital was conducted among labor ward staff (n=21) from November 1 to November 31, 2015. All observers classified ten cardiotocography traces according to the three guidelines using a bespoke form. Outcome measures included interobserver agreement (κ values), percentage agreement, intervention rate, and perceived ease of use. RESULTS: The κ values were 0.38 (FIGO 2015), 0.37 (NICE 2007), and 0.34 (NICE 2014). The percentage agreement was identical across the three systems for both normal cardiotocography results (100.0%) and for intermediate or suspicious results (80.9%). By contrast, the percentage agreement for abnormal or pathological findings was 47.6% for NICE 2014, 76.2% for FIGO 2015, and 91.0% for NICE 2007 guidelines. Among 210 observations, intervention was deemed necessary for 48 (22.9%) for FIGO 2015, 29 (13.8%) for NICE 2014, and 56 (26.7%) for NICE 2007 guidelines. The FIGO 2015 system was considered the easiest to use by 13 (61.9%) observers. CONCLUSION: Interobserver agreement of cardiotocography classification is suboptimal. The FIGO 2015 system offered favorable agreement scores, perceived ease of use, and a moderate intervention rate.

Study of positional dependence of dose to bladder, pelvic wall and rectal points in High-Dose-Rate Brachytherapy in cervical cancer patients.

The objective of the study is to examine the variation in doses to, Bladder, pelvic wall and Rectal Points when a patient is simulated in Supine (S Position) and Lithotomy M shaped positions (LM Position), respectively as part of Intracavitary Brachytherapy in Cervical Cancer patients. Patients (n = 19) were simulated and orthogonal images were taken in S Position and LM Positions on a physical simulator. Digital orthogonal X-ray images were transferred to Brachyvision Treatment Planning System via Dicom to generate treatment plans. Radio opaque dye of 7 ml was injected into the Foley bulb for identification and digitization of International Commission on Radiological Units and Measurements (ICRU) Bladder point. Pelvic side wall points were marked in accordance with ICRU 38 recommendations. A Rectal tube containing dummy source marker wire was used to identify Rectal Point. Students't-test was used to analyze the results. Doses in LM Position were lower and statistically significant when compared to S Position for ICRU Bladder Point, pelvic walls and Rectal Point. It was observed that movement of applicator could be the reason for the variations in doses between the two positions. Bladder, pelvic wall and rectal points systematically registered lower doses in LM Position as compared to S Position.

Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia.

BACKGROUND: Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1), endoglin (sEng) and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies. METHODOLOGY: To assess the effects of labour, samples were taken from 10 normal pregnant (NP) and 10 pre-eclamptic (PE) women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively. RESULTS: The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase. CONCLUSION: Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum.

Antepartum high-frequency fetal heart rate sinusoidal rhythm: computerized detection and fetal anemia.

OBJECTIVE: Our aim was to identify antepartum fetal heart rate (FHR) records of high-frequency (HF) sinusoidal rhythms from an electronic database (1983-2003) and determine clinical outcomes. STUDY DESIGN: At the John Radcliffe Hospital (Oxford, UK), 72,297 traces from 19,506 women were analyzed using an algorithm that identifies HF sinusoidal rhythms. The case records were reviewed. RESULTS: There were 15 (0.21/1000) traces from 8 (0.41/1000) women with an HF sinusoidal rhythm. In 5 of 8 women (62.5%), this pattern was associated with fetal anemia (hemoglobin < 10.0 g/dL). Their FHR patterns were distinguished from those of the other nonanemic fetuses by significantly lower long-term variability. CONCLUSION: An antepartum HF sinusoidal rhythm is rare but associated with fetal anemia, particularly if it is combined with reduced long-term variability without episodes of high FHR variability within 60 minutes. The automated system can alert inexperienced staff, who supervise FHR monitoring, by an online warning.