Tag: statistics

Med Image Anal. 2021 Jun 23;72:102145. doi: 10.1016/j.media.2021.102145. Online ahead of print.

ABSTRACT

PURPOSE: Artificial-intelligence population-based automated quantification of placental maturation and health from a rapid functional Magnetic Resonance scan. The placenta plays a crucial role for any successful human pregnancy. Deviations from the normal dynamic maturation throughout gestation are closely linked to major pregnancy complications. Antenatal assessment in-vivo using T2* relaxometry has shown great promise to inform management and possible interventions but clinical translation is hampered by time consuming manual segmentation and analysis techniques based on comparison against normative curves over gestation.

METHODS: This study proposes a fully automatic pipeline to predict the biological age and health of the placenta based on a free-breathing rapid (sub-30 second) T2* scan in two steps: Automatic segmentation using a U-Net and a Gaussian process regression model to characterize placental maturation and health. These are trained and evaluated on 108 3T MRI placental data sets, the evaluation included 20 high-risk pregnancies diagnosed with pre-eclampsia and/or fetal growth restriction. An independent cohort imaged at 1.5 T is used to assess the generalization of the training and evaluation pipeline.

RESULTS: Across low- and high-risk groups, automatic segmentation performs worse than inter-rater performance (mean Dice coefficients of 0.58 and 0.68, respectively) but is sufficient for estimating placental mean T2* (0.986 Pearson Correlation Coefficient). The placental health prediction achieves an excellent ability to differentiate cases of placental insufficiency between 27 and 33 weeks. High abnormality scores correlate with low birth weight, premature birth and histopathological findings. Retrospective application on a different cohort imaged at 1.5 T illustrates the ability for direct clinical translation.

CONCLUSION: The presented automatic pipeline facilitates a fast, robust and reliable prediction of placental maturation. It yields human-interpretable and verifiable intermediate results and quantifies uncertainties on the cohort-level and for individual predictions. The proposed machine-learning pipeline runs in close to real-time and, deployed in clinical settings, has the potential to become a cornerstone of diagnosis and intervention of placental insufficiency. APPLAUSE generalizes to an independent cohort imaged at 1.5 T, demonstrating robustness to different operational and clinical environments.

PMID:34229190 | DOI:10.1016/j.media.2021.102145

Eur J Obstet Gynecol Reprod Biol. 2021 Jun 20;263:198-204. doi: 10.1016/j.ejogrb.2021.06.022. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of our study was to assess the knowledge and attitudes toward expanded carrier screening (ECS) between the medical staff and general population in China.

STUDY DESIGN: It was a survey-based cross-sectional study in Chinese. We provided an online survey for the general public nationwide. We classified the population into the medical staff and general population to evaluate the knowledge gap and provide a reference for ECS’s education programs. Except for obstetrician-gynecologists and nurses in the department of Obstetrics and Gynecology, other medical staff were not included in our study. A total of 1947 questionnaires were collected from July 11, 2020 to February 10, 2021. Two hundred and eighty-four questionnaires were excluded from further analysis. The remaining 1663 cases were incorporated into the final analysis. Data were analyzed using IBM SPSS Statistics 26. Comparisons between categorical variables were tested by the use of crosstabs and χ2 test.

RESULTS: The total awareness rates of the knowledge about monogenic diseases and ECS in the respondents were low, with 35.7%, 26.1%, 3.3%, 23.3%, 24.1%, 55.2%, and 23.4% for questions Q1-Q7, respectively. Medical staff had more knowledge than general population. Knowledge about monogenic diseases and ECS was positively correlated with educational level. Most respondents showed a positive attitude toward ECS: 54.4% thought ECS was necessary, and 80.5% wanted to know more about monogenic diseases.

CONCLUSION: Although the public had little knowledge about monogenic disease and ECS, most of them showed a positive attitude. Our cross-analysis showed that medical staff had more knowledge compared to general population. Pre-test education for ECS can be carried out by medical staff who are not qualified for genetic counseling. ECS training for medical staff, especially obstetrician-gynecologist and nurse in the department of Obstetrics and Gynecology, can reduce the workload of genetic counseling.

PMID:34229183 | DOI:10.1016/j.ejogrb.2021.06.022

Eur J Obstet Gynecol Reprod Biol. 2021 Jun 25;263:205-209. doi: 10.1016/j.ejogrb.2021.06.029. Online ahead of print.

ABSTRACT

OBJECTIVE: Women undergoing assisted reproductive treatment are usually concerned about the side effects caused by high doses of gonadotropin. A common inquiry of patients is concerning the weight gain as a consequence. The aim of this study was to evaluate if controlled ovarian stimulation increase the weight of women undergoing IVF treatment. Study design This retrospective cohort study included 734 women undergoing IVF treatment between January 2017 and May 2018 and had body weight measured on the day of ovarian stimulation starting (basal-weight) and on the hCG trigger day (hCG-weight). The difference of hCG-weight and basal-weight was calculated and correlated to number of oocytes retrieved and ovarian stimulation protocol. For 358 women, two international validated questionnaires to evaluate the anxiety and binge eating were applied at the end of ovarian stimulation and also associated to the body weight gain.

RESULTS: The basal-weight and hCG-weight were paired compared and demonstrate a statistically significant weight gain from basal to hCG-weight of a mean of 387.7 ± 720.4 g (p < 0.001). The weight gain had a positive correlation with the number of oocytes retrieved (Pearson correlation, r = 0.181; p < 0.001) but no correlation with the ovarian stimulation protocol. Regarding the questionnaires answered by patients, neither anxiety score (Pearson: r = -0,031; p = 0,561) nor binge eating score (Pearson: r = 0,069; p = 0,199) were correlated with weight gain from basal-weight to hCG- weight. However, patients who felt eating more during the treatment had a higher weight gain (p < 0.001) independently of the number of oocytes retrieved.

CONCLUSIONS: The weight gain is possibly a result from edema and is clinically irrelevant despite of the statistical significance and will probably be resolved in some days after oocytes retrieval. A small “weight gain” was observed and associated to the number of oocytes retrieved regardless of protocol and medication used in the ovarian stimulation.

PMID:34229184 | DOI:10.1016/j.ejogrb.2021.06.029

Ecotoxicol Environ Saf. 2021 Jun 30;222:112481. doi: 10.1016/j.ecoenv.2021.112481. Online ahead of print.

ABSTRACT

Due to the COVID-19 outbreak, the Chinese government implemented nationwide traffic restrictions and self-quarantine measures from January 23 to April 8 (in Wuhan), 2020. We estimated how these measures impacted ambient air pollution and the subsequent consequences on health and the health-related economy in 367 Chinese cities. A random forests modeling was used to predict the business-as-usual air pollution concentrations in 2020, after adjusting for the impact of long-term trend and weather conditions. We calculated changes in mortality attributable to reductions in air pollution in early 2020 and health-related economic benefits based on the value of statistical life (VSL). Compared with the business-as-usual scenario, we estimated 1239 (95% CI: 844-1578) PM_2.5-related deaths were avoided, as were 2777 (95% CI: 1565-3995) PM₁₀-related deaths, 1587 (95% CI: 98-3104) CO-related deaths, 4711 (95% CI: 3649-5781) NO₂-related deaths, 215 (95% CI: 116-314) O₃-related deaths, and 1088 (95% CI: 774-1421) SO₂-related deaths. Based on the reduction in deaths, economic benefits for in PM_2.5, PM₁₀, CO, NO₂, O₃, and SO₂ were 1.22, 2.60, 1.36, 4.05, 0.20, and 0.95 billion USD, respectively. Our findings demonstrate the substantial benefits in human health and health-related costs due to improved urban air quality during the COVID lockdown period in China in early 2020.

PMID:34229169 | DOI:10.1016/j.ecoenv.2021.112481

J Mech Behav Biomed Mater. 2021 Jun 29;122:104666. doi: 10.1016/j.jmbbm.2021.104666. Online ahead of print.

ABSTRACT

Teeth are the hardest part of the human body. Cracking of human teeth under compression progresses by avalanches emitting acoustic noise. Acoustic emission (AE) spectroscopy reveals that tooth avalanches are statistically fully compatible with predictions of mean field (MF) theory. Avalanche energies collapse into a power law distributed which is stable over more than five decades with an energy exponent ε = 1.4. Acoustic amplitudes (exponent ~τ), durations (~α), correlations between amplitudes and energies (~x), and correlations between amplitude and duration (~χ) follow equally power laws with MF values of all exponents. The exponents correlation: τ-1 = x(ε-1) = (α-1)/χ is confirmed. Crack propagation bifurcates and shows the hallmarks of avalanches where main cracks nucleate secondary cracks.

PMID:34229170 | DOI:10.1016/j.jmbbm.2021.104666

Forensic Sci Int. 2021 Jun 24;325:110883. doi: 10.1016/j.forsciint.2021.110883. Online ahead of print.

ABSTRACT

In post-mortem investigations of fatal intoxication, it is challenging to determine which drug(s) were responsible for the death, and which drugs did not. This study aims to provide post-mortem femoral blood drug levels in lethal intoxication and in post-mortem control cases, where the cause of death was other than intoxication. The reference values could assist in the interpretation of toxicological results in the routine casework. To this end, all post-mortem toxicological results in femoral blood from 2011 to 2017 in Western Switzerland were considered. A full autopsy with systematic toxicological analysis (STA) was conducted in all cases. Results take into account the cause of death classified into one of four categories (as published by Druid and colleagues): I) certified intoxication by one substance alone, IIa) certified intoxication by more than one substance, IIb) certified other causes of death with incapacitation due to drugs, and III) certified other causes of death without incapacitation due to drugs. This study includes 1 990 post-mortem cases where femoral blood was analysed. The material comprised 619 women (31%) and 1 371 men (69%) with a median age of 50 years. The concentrations of the 32 most frequently recorded substances as well as alcohol are discussed. These include 6 opioids and opiates, 3 antidepressants, 6 neuroleptics and hypnotics, 1 barbiturate, 11 benzodiazepines (and related drugs), 2 amphetamine-type stimulants, cocaine, paracetamol, and tetrahydrocannabinol (THC). The most common substances that caused intoxication alone were morphine, methadone, ethanol, tramadol, and cocaine. The post-mortem concentration ranges for all substance are categorized as I, IIa, IIb, or III. Statistical post-mortem reference concentrations for drugs are discussed and compared with previously published concentrations. This study shows that recording and classifying cases is time-consuming, but it is rewarding in a long-term perspective to achieve a more reliable information about fatal and non-fatal blood concentrations.

PMID:34229141 | DOI:10.1016/j.forsciint.2021.110883

Epilepsy Behav. 2021 Jul 3;122:108159. doi: 10.1016/j.yebeh.2021.108159. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to investigate the semiology of seizure disorders, including electroencephalographic characteristics, and seizure outcomes in participants with anti-leucine-rich glioma-inactivated 1 (LGI-1) encephalitis.

METHODS: Seventy participants who presented with seizures during the acute phase of anti-LGI-1 encephalitis at Peking Union Medical College Hospital from May 2013 to July 2020 were reviewed. All participants underwent follow-up for longer than 2 years.

RESULTS: At the time of presentation, 48 (68.6%) participants had generalized seizures and 57 (81.4%) had focal seizures. The most common focal motor seizures were faciobrachial dystonic seizures (FDS). The main manifestations of focal nonmotor seizures were dyscognitive features, goosebumps, and disorders of sensation. All participants received immunomodulatory therapy. Thirty-five (50%) participants were seizure free after 1 year of follow-up, and 48 (68.6%) participants were seizure free over a follow-up of 2 years. Participants with seizures continued longer than 1 year were older than participants whose seizure duration was shorter than 1 year (P = 0.021). However, after an extended follow-up period, the difference between the incidences of seizures based on age was not significant. The frequency of focal motor seizures was higher in participants who became seizure free within 1 year, compared to participants who had seizures for longer than 1 year (75% vs 54.3%, respectively; P = 0.015). Participants with seizures continued over 2 years tended to have focal nonmotor seizures, and tended to show an elevated incidence of abnormal EEG results. Participants receiving early corticosteroid and longer duration immunosuppressant treatments, tended to have a lower risk of persistent seizures and better seizure outcomes, with no statistical significance.

CONCLUSIONS: Most participants obtained remission from seizures after immunomodulatory therapy. The seizure manifestation of anti-LGI1 encephalitis is diverse and variable. The type of focal seizures may affect the outcome of participants with seizures. Older age could lead to longer duration of the seizure disorder, but did not affect the rate of seizures over the long term. Early and prolonged administration of immunomodulatory therapy may be useful for shortening the time to becoming seizure free.

PMID:34229158 | DOI:10.1016/j.yebeh.2021.108159

Int J Hyg Environ Health. 2021 Jul 3;236:113800. doi: 10.1016/j.ijheh.2021.113800. Online ahead of print.

ABSTRACT

Although several studies indicate that exposure to polybrominated diphenyl ethers (PBDEs) and metals may influence thyroid function, the evidence is limited and inconsistent in general population. The current study was conducted to determine the levels of plasma PBDEs and urinary metals and evaluate the associations of co-exposure to both with thyroid hormones (THs) among rural adult residents along the Yangtze River, China. A total of 329 subjects were included in current analyses, and 8 PBDEs congeners and 14 urinary metals were measured to reflect the levels of environmental exposure. Multiple linear regression models were used to evaluate the association between PBDEs, metals and THs levels. Bayesian Kernel Machine Regression (BKMR) was used to examine PBDEs and metals mixtures in relation to THs. The geometric mean (GM) and 95% confidence interval (CI) of total measured PBDEs was 65.10 (59.96, 70.68) ng/g lipid weights (lw). BDE-209 was the most abundant congener, with a GM (95% CI) of 47.91 (42.95, 53.26) ng/g lw, accounting for 73.6% of the total PBDEs. Free thyroxine (FT4) was significantly negatively associated with BDE-28, 47, 99, 100, 154, and 183, and urinary strontium [β (95% CI): -0.04 (-0.07, -0.02)], but positively associated with selenium [β (95% CI): 0.04 (0.02, 0.06)]. Free triiodothyronine (FT3) was negatively associated with BDE-28 [β (95% CI): -0.03 (-0.05, -0.01)] and urinary arsenic [β (95% CI): -0.01 (-0.02, -0.001)]. The current study did not observe a statistically significant association of thyroid-stimulating hormone (TSH) with PBDEs and urinary metals. BKMR analyses showed similar trends when these chemicals were taken into consideration simultaneously. We found no significant interaction in the association between individual chemical at the 25th versus 75th percentiles and THs estimates, comparing the results when other chemicals were set at their 10th, 50th, and 90th percentile levels. Further study is required to confirm these findings and determine potential mechanisms.

PMID:34229161 | DOI:10.1016/j.ijheh.2021.113800

Breast. 2021 Jun 28;59:117-123. doi: 10.1016/j.breast.2021.06.009. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the effect of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging on chemotherapy decision-making for triple-negative breast cancer (TNBC) patients with T1-2N0M0 disease.

METHODS: Patients diagnosed with T1-2N0M0 TNBC were retrieved from the Surveillance, Epidemiology, and End Results program. Statistical methods including Kaplan-Meier survival curve, receiver operating characteristics curve, and Cox proportional hazard model.

RESULTS: We identified 12,156 patients, including 9371 (77.1%) patients who received chemotherapy. Overall, 57.4% of patients (n = 6975) were upstaged after being reassigned by the 8th AJCC staging. However, the 8th staging of AJCC did not have a greater prognostic value compared to the 7th staging (P = 0.064). The receipt of chemotherapy significantly improved the breast cancer-specific survival for stage T1c and T2 tumors (P < 0.001), but not for stage T1a (P = 0.188) and T1b (P = 0.376) tumors. Using AJCC 8th staging, chemotherapy benefit was only found in stage IIA patients (P = 0.002), but not for stage IA (P = 0.653) and IB (P = 0.492) patients. There were 9564 patients with stage T1c and T2 diseases and 4979 patients with 8th AJCC stage IIA disease. Therefore, approximately half of patients (47.9%, n = 4585) may be safe to omit chemotherapy using the AJCC 8th staging compared to the current chemotherapy recommendation for T1-2N0M0 TNBC.

CONCLUSION: The 8th AJCC staging system did not demonstrate the superior discriminatory ability of prognostic stratification than the 7th AJCC staging system in T1-2N0M0 TNBC. However, this new AJCC staging could more accurately predict the chemotherapy benefit, thereby enabling more patients to avoid unnecessary chemotherapy.

PMID:34229126 | DOI:10.1016/j.breast.2021.06.009

Se Pu. 2021 Apr 8;39(4):391-398. doi: 10.3724/SP.J.1123.2020.06018.

ABSTRACT

Urine is an important source of biomolecular information for metabolomic studies. However, the acquisition of high-quality metabolomic datasets or reliable biomarkers from urine is difficult owing to the large variations in the concentrations of endogenous metabolites in the biofluid, which are caused by diverse factors such as water consumption, drugs, and diseases. Thus, normalization or calibration is essential in urine metabolomics for eliminating such deviations. The urine osmolality (Π), which is a direct measure of the total urinary solute concentration and is not affected by circadian rhythms, diet, gender, and age, is often considered the gold standard for estimation of the urine concentration. In this study, a pre-data acquisition calibration strategy based on osmolality was investigated for its feasibility to overcome sample concentration variability. Before data acquisition, the product of the osmolality×injection volume of all samples was set to be equivalent through the uses of a customized injection volume or dilution. After ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) analysis of the sample, the raw dataset was normalized to the total ion abundance or total useful MS signals (MSTUS) to achieve further calibration. The osmolality of each urine sample was determined with a freezing-point depression osmometer. For the instrumental analysis, a Vanquish UPLC system coupled to a Q-Exactive Plus HRMS device was used for metabolite analysis and accurate mass measurement. Full-scan mass spectra were acquired in the range of m/z 60-900, and the MS/MS experiments were conducted in “Top5” data-dependent mode. A Waters UPLC column (100 mm×2.1 mm, 1.8 μm) was used for chromatography separation. The raw data were imported into Progenesis QI software for peak picking, alignment, deconvolution, and normalization. SIMCA-P software was used for the principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA). This strategy was first applied to sequentially diluted urine samples, where three frequently used normalization methods were compared. In the identical injection volume experiment, the points were scattered and showed relevant distribution according to the dilution multiple in the plot of PCA scores. There was little improvement after normalization to either the total ion abundance or MSTUS. In the customized injection volume experiment, the urine samples derived from the same source showed ideal clustering. With total ion abundance and MSTUS normalization, the dataset was further improved in the PCA model fitting and prediction. As a result, there were more peaks with a peak area RSD of <30%, which indicated better parallelism. The diluted urine solutions had higher Spearman’s coefficient values with their sample source than those without calibration, which suggested less intra-group differences. The strategy was further validated using data from a metabolomic study of children with congenital hydronephrosis and healthy controls. As a concentration estimator, osmolality showed better linear correlation with the mass signal and was less influenced by physiological or pathological factors, thus obtaining broader application and more accurate results than creatinine. The concentration variability was effectively eliminated after customized dilution calibration and showed a more obvious clustering effect in the PCA score plot. The OPLS-DA-based statistical model used to identify discriminate metabolites was improved, with less chance of overfitting. In conclusion, the calibration strategy based on osmolality combined with total ion abundance or MSTUS normalization significantly overcame the problem of urine concentration variability, eliminated intra-group differences, and possessed better parallelism, thus giving better clustering effects in PCA or OPLS-DA and higher reliability of the statistical model. The results of this study provide guidance and a reference for future metabolomic studies on urine.

PMID:34227759 | DOI:10.3724/SP.J.1123.2020.06018