Clinical evaluation of droplet digital PCR in the early identification of suspected sepsis patients in the emergency department: a prospective observational study.

Background: Rapid and accurate diagnosis of the causative agents is essential for clinical management of bloodstream infections (BSIs) that might induce sepsis/septic shock. A considerable number of suspected sepsis patients initially enter the health-care system through an emergency department (ED), hence it is vital to establish an early strategy to recognize sepsis and initiate prompt care in ED. This study aimed to evaluate the diagnostic performance and clinical value of droplet digital PCR (ddPCR) assay in suspected sepsis patients in the ED. Methods: This was a prospective single-centered observational study including patients admitted to the ED from 25 October 2022 to 3 June 2023 with suspected BSIs screened by Modified Shapiro Score (MSS) score. The comparison between ddPCR and blood culture (BC) was performed to evaluate the diagnostic performance of ddPCR for BSIs. Meanwhile, correlative analysis between ddPCR and the inflammatory and prognostic-related biomarkers were conducted to explore the relevance. Further, the health economic evaluation of the ddPCR was analyzed. Results: 258 samples from 228 patients, with BC and ddPCR performed simultaneously, were included in this study. We found that ddPCR results were positive in 48.13% (103 of 214) of episodes, with identification of 132 pathogens. In contrast, BC only detected 18 positives, 88.89% of which were identified by ddPCR. When considering culture-proven BSIs, ddPCR shows an overall sensitivity of 88.89% and specificity of 55.61%, the optimal diagnostic power for quantifying BSI through ddPCR is achieved with a copy cutoff of 155.5. We further found that ddPCR exhibited a high accuracy especially in liver abscess patients. Among all the identified virus by ddPCR, EBV has a substantially higher positive rate with a link to immunosuppression. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity as well as prognosis. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs. Conclusions: The multiplexed ddPCR delivers precise and quantitative load data on the causal pathogen, offers the ability to monitor the patient's condition and may serve as early warning of sepsis in time-urgent clinical situations as ED. Importance: Early detection and effective administration of antibiotics are essential to improve clinical outcomes for those with life-threatening infection in the emergency department. ddPCR, an emerging tool for rapid and sensitive pathogen identification used as a precise bedside test, has developed to address the current challenges of BSI diagnosis and precise treatment. It characterizes sensitivity, specificity, reproducibility, and absolute quantifications without a standard curve. ddPCR can detect causative pathogens and related resistance genes in patients with suspected BSIs within a span of three hours. In addition, it can identify polymicrobial BSIs and dynamically monitor changes in pathogenic microorganisms in the blood and can be used to evaluate antibiotic efficacy and survival prognosis. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs.

Dynamic cerebral blood flow assessment based on electromagnetic coupling sensing and image feature analysis.

Dynamic assessment of cerebral blood flow (CBF) is crucial for guiding personalized management and treatment strategies, and improving the prognosis of stroke. However, a safe, reliable, and effective method for dynamic CBF evaluation is currently lacking in clinical practice. In this study, we developed a CBF monitoring system utilizing electromagnetic coupling sensing (ECS). This system detects variations in brain conductivity and dielectric constant by identifying the resonant frequency (RF) in an equivalent circuit containing both magnetic induction and electrical coupling. We evaluated the performance of the system using a self-made physical model of blood vessel pulsation to test pulsatile CBF. Additionally, we recruited 29 healthy volunteers to monitor cerebral oxygen (CO), cerebral blood flow velocity (CBFV) data and RF data before and after caffeine consumption. We analyzed RF and CBFV trends during immediate responses to abnormal intracranial blood supply, induced by changes in vascular stiffness, and compared them with CO data. Furthermore, we explored a method of dynamically assessing the overall level of CBF by leveraging image feature analysis. Experimental testing substantiates that this system provides a detection range and depth enhanced by three to four times compared to conventional electromagnetic detection techniques, thereby comprehensively covering the principal intracranial blood supply areas. And the system effectively captures CBF responses under different intravascular pressure stimulations. In healthy volunteers, as cerebral vascular stiffness increases and CO decreases due to caffeine intake, the RF pulsation amplitude diminishes progressively. Upon extraction and selection of image features, widely used machine learning algorithms exhibit commendable performance in classifying overall CBF levels. These results highlight that our proposed methodology, predicated on ECS and image feature analysis, enables the capture of immediate responses of abnormal intracranial blood supply triggered by alterations in vascular stiffness. Moreover, it provides an accurate diagnosis of the overall CBF level under varying physiological conditions.

In-vitro assessment of a novel plant rhizobacterium, Citrobacter freundii, for degrading and biocontrol of food mycotoxin deoxynivalenol.

Deoxynivalenol (DON) is one of the most harmful and well-known toxins present in food and animal feed throughout the world. Citrobacter freundii (C. freundii-ON077584), a novel DON-degrading strain, was isolated from rice root-linked soil samples. The degrading properties, including DON concentrations, incubation pH, incubation temperatures, bacterial concentrations, and acid treatment effect on degradation, were evaluated. At pH 7 and an incubation temperature of 37 °C, C. freundii demonstrated the capability to degrade more than 90% of DON. The degraded products of DON were identified as 3-keto-DON and DOM-1, which were confirmed by High Performance Liquid Chromatography (HPLC) and Ultra-Performance Liquid Chromatography hyphenated with Tandem Mass Spectrometry (UPLC-MS/MS) analyses. The mechanism of DON degradation into 3-keto-DON and DOM-1 by this bacterial strain will be further explored to identify and purify novel degrading enzymes that can be cloned to the microorganism and added to the animal feed to degrade the DON in the digestion tract.

Analysing the Effect of Energy Intensity on Carbon Emission Reduction in Beijing.

Beijing has experienced rapid economic development since the reforms and opening up. However, the traditional development model based on excessive energy consumption has posed great challenges to the ecological environment. To curb environmental degradation and achieve sustainable social development, Beijing has proposed to achieve carbon neutrality by 2050. As an important indicator of energy consumption, it is necessary to clarify how energy intensity (EI) affects carbon emissions (CE) to achieve carbon neutrality in Beijing by 2050. This study first decomposes the drivers of CE in Beijing from 2010 to 2020 using the logarithmic mean Divisia index (LMDI) method and comparatively analyses the impact of EI on CE. Then, the spatial Dubin model (SDM) is used to analyse the spatial spillover effect of EI on CE at the regional level. Finally, the macro moderating role of economic development in the effect of EI on CE is analysed. The results show that the effect of EI has been the main driver of CE reduction in Beijing. Among the industrial sectors, manufacturing and transportation have had the greatest success in reducing CE through EI reduction. At the regional level, there is a spatial spillover effect of EI on CE, and the effect of carbon reduction through the spillover effect of EI is greater than the direct effect of EI. Economic factors have an enhanced moderating effect on the process of EI affecting CE, and this moderating effect has threshold properties.

Health Effects of Happiness in China.

The demand for improving health status of Chinese residents is growing with the rapid economic development. Happiness, which could be improved by some brief, self-administered, and cost-effective interventions, is reported to be associated with mortality, longevity, and self-rated health. Therefore, it is essential to assess the effect of happiness on health in China. Using data from the Chinese General Social Survey 2017, the present study explored the effect of happiness on health among Chinese residents after controlling for demographic variables, socioeconomic factors, social relationships, locations, and insurance plan. The happiness effect across subsamples by age and resident type and the mediator role of happiness were also evaluated. Based on an ordered probit regression model, we found that the effect of happiness on health was significantly positive in full sample and all subsamples. Using a structural equation model, we demonstrated that happiness could partially mediate the relationship between socioeconomic factors, social relationships factors, and health. Our data supplement the existing literature on the relationship between happiness and health and provide evidence for policymakers and stakeholders focusing on happiness as a health strategy to improve overall societal wellbeing.

Early assessment of acute ischemic stroke in rabbits based on multi-parameter near-field coupling sensing.

BACKGROUND: Early diagnosis and continuous monitoring are the key to emergency treatment and intensive care of patients with acute ischemic stroke (AIS). Nevertheless, there has not been a fully accepted method targeting continuous assessment of AIS in clinical. METHODS: Near-field coupling (NFC) sensing can obtain the conductivity related to the volume of intracranial components with advantages of non-invasiveness, strong penetrability and real-time monitoring. In this work, we built a multi-parameter monitoring system that is able to measure changes of phase and amplitude in the process of electromagnetic wave (EW) reflection and transmission. For investigating its feasibility in AIS detection, 16 rabbits were chosen to establish AIS models by bilateral common carotid artery ligation and then were enrolled for monitoring experiments. RESULTS: During the 6 h after AIS, the reflection amplitude (RA) shows a decline trend with a range of 0.69 dB and reflection phase (RP) has an increased variation of 6.48° . Meanwhile, transmission amplitude (TA) and transmission phase (TP) decrease 2.14 dB and 24.29° , respectively. The statistical analysis illustrates that before ligation, 3 h after ligation and 6 h after ligation can be effectively distinguished by the four parameters individually. When all those parameters are regarded as recognition features in back propagation (BP) network, the classification accuracy of the three different periods reaches almost 100%. CONCLUSION: These results prove the feasibility of multi-parameter NFC sensing to assess AIS, which is promised to become an outstanding point-of-care testing method in the future.

A noninvasive and comprehensive method for continuous assessment of cerebral blood flow pulsation based on magnetic induction phase shift.

Cerebral blood flow (CBF) monitoring is of great significance for treating and preventing strokes. However, there has not been a fully accepted method targeting continuous assessment in clinical practice. In this work, we built a noninvasive continuous assessment system for cerebral blood flow pulsation (CBFP) that is based on magnetic induction phase shift (MIPS) technology and designed a physical model of the middle cerebral artery (MCA). Physical experiments were carried out through different simulations of CBF states. Four healthy volunteers were enrolled to perform the MIPS and ECG synchronously monitoring trials. Then, the components of MIPS related to the blood supply level and CBFP were investigated by signal analysis in time and frequency domain, wavelet decomposition and band-pass filtering. The results show that the time-domain baseline of MIPS increases with blood supply level. A pulse signal was identified in the spectrum (0.2-2 Hz in 200-2,000 ml/h groups, respectively) of MIPS when the simulated blood flow rate was not zero. The pulsation frequency with different simulated blood flow rates is the same as the squeezing frequency of the feeding pump. Similar to pulse waves, the MIPS signals on four healthy volunteers all had periodic change trends with obvious peaks and valleys. Its frequency is close to that of the ECG signal and there is a certain time delay between them. These results indicate that the CBFP component can effectively be extracted from MIPS, through which different blood supply levels can be distinguished. This method has the potential to become a new solution for non-invasive and comprehensive monitoring of CBFP.

The Impact of Green Technology Innovation on Carbon Emissions in the Context of Carbon Neutrality in China: Evidence from Spatial Spillover and Nonlinear Effect Analysis.

The Paris agreement is a unified arrangement for the global response to climate change and entered into force on 4 November 2016. Its long-term goal is to hold the global average temperature rise well below 2 °C. China is committed to achieving carbon neutrality by 2060 through various measures, one of which is green technology innovation (GTI). This paper aims to analyze the levels of GTI in 30 provinces in mainland China between 2001 and 2019. It uses the spatial econometric models and panel threshold models along with the slack based measure (SBM) and Global Malmquist-Luenberger (GML) index to analyze the spatial spillover and nonlinear effects of GTI on regional carbon emissions. The results show that GTI achieves growth every year, but the innovation efficiency was low. China's total carbon dioxide emissions were increasing at a marginal rate, but the carbon emission intensity was declining year by year. Carbon emissions were spatially correlated and show significant positive agglomeration characteristics. The spatial spillover of GTI plays an important role in reducing carbon dioxide emissions. In the underdeveloped regions in China, this emission reduction effect was even more significant.

Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. METHOD: Adult subjects (N = 2229; 56.2% male) aged 18-69 years (mean = 35.6, SD = 11.0) from 21 ENIGMA-PGC PTSD sites underwent T1-weighted brain structural magnetic resonance imaging, and PTSD assessment (PTSD+, n = 884). Previously trained voxel-wise (brainageR) and region-of-interest (BARACUS and PHOTON) machine learning pipelines were compared in a subset of control subjects (n = 386). Linear mixed effects models were conducted in the full sample (those with and without PTSD) to examine the effect of PTSD on brain predicted age difference (brain PAD; brain age - chronological age) controlling for chronological age, sex, and scan site. RESULTS: BrainageR most accurately predicted brain age in a subset (n = 386) of controls (brainageR: ICC = 0.71, R = 0.72, MAE = 5.68; PHOTON: ICC = 0.61, R = 0.62, MAE = 6.37; BARACUS: ICC = 0.47, R = 0.64, MAE = 8.80). Using brainageR, a three-way interaction revealed that young males with PTSD exhibited higher brain PAD relative to male controls in young and old age groups; old males with PTSD exhibited lower brain PAD compared to male controls of all ages. DISCUSSION: Differential impact of PTSD on brain PAD in younger versus older males may indicate a critical window when PTSD impacts brain aging, followed by age-related brain changes that are consonant with individuals without PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan.

Fishes regulate tail-beat kinematics to minimize speed-specific cost of transport.

Energetic expenditure is an important factor in animal locomotion. Here we test the hypothesis that fishes control tail-beat kinematics to optimize energetic expenditure during undulatory swimming. We focus on two energetic indices used in swimming hydrodynamics, cost of transport and Froude efficiency. To rule out one index in favour of another, we use computational-fluid dynamics models to compare experimentally observed fish kinematics with predicted performance landscapes and identify energy-optimized kinematics for a carangiform swimmer, an anguilliform swimmer and larval fishes. By locating the areas in the predicted performance landscapes that are occupied by actual fishes, we found that fishes use combinations of tail-beat frequency and amplitude that minimize cost of transport. This energy-optimizing strategy also explains why fishes increase frequency rather than amplitude to swim faster, and why fishes swim within a narrow range of Strouhal numbers. By quantifying how undulatory-wave kinematics affect thrust, drag, and power, we explain why amplitude and frequency are not equivalent in speed control, and why Froude efficiency is not a reliable energetic indicator. These insights may inspire future research in aquatic organisms and bioinspired robotics using undulatory propulsion.

Noninvasive real-time assessment of intracranial pressure after traumatic brain injury based on electromagnetic coupling phase sensing technology.

BACKGROUND: To investigate the feasibility of intracranial pressure (ICP) monitoring after traumatic brain injury (TBI) by electromagnetic coupling phase sensing, we established a portable electromagnetic coupling phase shift (ECPS) test system and conducted a comparison with invasive ICP. METHODS: TBI rabbits' model were all synchronously monitored for 24 h by ECPS testing and invasive ICP. We investigated the abilities of the ECPS to detect targeted ICP by feature extraction and traditional classification decision algorithms. RESULTS: The ECPS showed an overall downward trend with a variation range of - 13.370 ± 2.245° as ICP rose from 11.450 ± 0.510 mmHg to 38.750 ± 4.064 mmHg, but its change rate gradually declined. It was greater than 1.5°/h during the first 6 h, then decreased to 0.5°/h and finally reached the minimum of 0.14°/h. Nonlinear regression analysis results illustrated that both the ECPS and its change rate decrease with increasing ICP post-TBI. When used as a recognition feature, the ability (area under the receiver operating characteristic curve, AUCs) of the ECPS to detect ICP ≥ 20 mmHg was 0.88 ± 0.01 based on the optimized adaptive boosting model, reaching the advanced level of current noninvasive ICP assessment methods. CONCLUSIONS: The ECPS has the potential to be used for noninvasive continuous monitoring of elevated ICP post-TBI.

Spatio-Temporal Variation of Health Production Efficiency Considering Environmental Pollution in China Based on Modified EBM and Spatial Econometric Model.

In order to strengthen the construction of China's health industry and improve the health of the people, based on the data of 31 provinces and cities in China from 2009 to 2019, the improved EBM model is used to measure the health production efficiency of each region, and Moran index is used to study the Spatio-temporal variation of health production efficiency of each province. Finally, the spatial econometric model is applied to study the influencing factors of the Spatio-temporal variation of health production efficiency. The results show that generally speaking, the average efficiency of 31 provinces and cities is above 0.7, and the average efficiency of some regions is above 1. From the perspective of time variation, the average efficiency value in the eastern region and the middle region increases from 0.816 to 0.882 and from 0.851 to 0.861, respectively. However, the average efficiency value in the western region and northeast region decreases from 0.861 to 0.83 and from 0.864 to 0.805, respectively. From the perspective of spatial distribution, HH agglomeration and LL agglomeration exist in most regions. By comparing Moran scatter plots in 2009 and 2019, it is found that the quadrants of most regions remain unchanged, and LL agglomeration is the main agglomeration type in local space. There is a significant spatial dependence among different regions. From the perspective of spatial empirical results, Pgdp, Med, and Pd have a positive effect on health production efficiency. The direct effect and indirect effect of Pgdp, Med, and Gov all pass the significance test of 1%, indicating that there are spatial spillover effects of the three indicators. Each region should reasonably deal with the spillover effect of surrounding regions, vigorously develop economic activities, carry out cooperation with surrounding regions and apply demonstration effect to accelerate the development of overall health production.

Allocation of pharmaceutical resources in maternal and child healthcare institutions during the COVID-19 pandemic.

Since the outbreak of a cluster of patients with pneumonia of unknown cause in Wuhan, Hubei Province, China, in December 2019, the disease was later officially named coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), quickly spreading globally. Pregnant women and children are particularly vulnerable during disasters and emergencies. Comprehensive and applicable emergency preparedness and response are definitely important methods to prevent and contain the COVID-19 pandemic. The rational allocation of pharmaceutical resources plays an important role in the medical emergency plan. This paper aimed to share experiences for the allocation of pharmaceutical resources in hospitals focusing primarily on women and children during the COVID-19 pandemic.

Patient satisfaction survey scores are not an appropriate metric to differentiate performance among anesthesiologists.

STUDY OBJECTIVE: With the focus of patient-centered care in healthcare organizations, patient satisfaction plays an increasingly important role in healthcare quality measurement. We sought to determine whether an automated patient satisfaction survey could be effectively used to identify outlying anesthesiologists. DESIGN: Retrospective Observational Study. SETTING: Vanderbilt University Medical Center (VUMC). MEASUREMENTS: Patient satisfaction data were obtained between October 24, 2016 and November 1, 2017. A multivariable ordered probit regression was conducted to evaluate the relationship between the mean scores of responses to Likert-scale questions on SurveyVitals' Anesthesia Patient Satisfaction Questionnaire 2. Fixed effects included demographics, clinical variables, providers and surgeons. Hypothesis tests to compare each individual anesthesiologist with the median-performing anesthesiologist were conducted. MAIN RESULTS: We analyzed 10,528 surveys, with a 49.5% overall response rate. Younger patient (odds ratio (OR) 1.011 [per year of age]; 95% confidence interval (CI) 1.008 to 1.014; p < 0.001), regional anesthesia (versus general anesthesia) (OR 1.695; 95% CI 1.186 to 2.422; p = 0.004) and daytime surgery (versus nighttime surgery) (OR 1.795; 95% CI 1.091 to 2.959; p = 0.035) were associated with higher satisfaction scores. Compared with the median-ranked anesthesiologist, we found the adjusted odds ratio for an increase in satisfaction score ranged from 0.346 (95% CI 0.158 to 0.762) to 1.649 (95% CI 0.687 to 3.956) for the lowest and highest scoring providers, respectively. Only 10.10% of anesthesiologists at our institution had an odds ratio for satisfaction with a 95% CI not inclusive of 1. CONCLUSIONS: Patient satisfaction is impacted by multiple factors. There was very little information in patient satisfaction scores to discriminate the providers, after adjusting for confounding. While patient satisfaction scores may facilitate identification of extreme outliers among anesthesiologists, there is no evidence that this metric is useful for the routine evaluation of individual provider performance.

Allocation of pharmaceutical resources in maternal and child healthcare institutions during the COVID-19 pandemic

SUMMARY Since the outbreak of a cluster of patients with pneumonia of unknown cause in Wuhan, Hubei Province, China, in December 2019, the disease was later officially named coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), quickly spreading globally. Pregnant women and children are particularly vulnerable during disasters and emergencies. Comprehensive and applicable emergency preparedness and response are definitely important methods to prevent and contain the COVID-19 pandemic. The rational allocation of pharmaceutical resources plays an important role in the medical emergency plan. This paper aimed to share experiences for the allocation of pharmaceutical resources in hospitals focusing primarily on women and children during the COVID-19 pandemic.

RESUMO Desde o aparecimento de um aglomerado de doentes com pneumonia de causa desconhecida em Wuhan, província de Hubei, China, em dezembro de 2019, a doença foi mais tarde oficialmente nomeada doença do coronavírus 2019 (Covid-19), causada pelo novo vírus da síndrome respiratória aguda grave coronavírus (Sars-CoV-2), que rapidamente se espalhou em nível mundial. As mulheres grávidas e as crianças são particularmente vulneráveis durante catástrofes e emergâncias. A preparação e a resposta de emergência abrangentes e aplicáveis são métodos definitivamente importantes para prevenir e conter a pandemia de Covid-19. A alocação racional dos recursos farmacêuticos desempenha um papel importante no plano de emergência médica. Este documento objetivou compartilhar experiências para a alocação de recursos farmacêuticos em hospitais focando principalmente mulheres e crianças durante a pandemia de Covid-19.

Fast-track multidisciplinary treatment versus conventional treatment for colorectal cancer: a multicenter, open-label randomized controlled study.

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.

Burden of neurological and neurocognitive impairment in pediatric sickle cell anemia in Uganda (BRAIN SAFE): a cross-sectional study.

BACKGROUND: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations in sub-Saharan Africa are limited. METHODS: We aimed to establish the frequency and types of pediatric brain injury in a cross-sectional study at a large SCA clinic in Kampala, Uganda in a randomly selected sample of 265 patients with HbSS ages 1-12 years. Brain injury was defined as one or more abnormality on standardized testing: neurocognitive impairment using an age-appropriate test battery, prior stroke by examination or transcranial Doppler (TCD) velocities associated with stroke risk in children with SCA (cerebral arterial time averaged mean maximum velocity ≥ 170 cm/second). RESULTS: Mean age was 5.5 ± 2.9 years; 52.3% were male. Mean hemoglobin was 7.3 ± 1.01 g/dl; 76.4% had hemoglobin < 8.0 g/dl. Using established international standards, 14.7% were malnourished, and was more common in children ages 5-12. Overall, 57 (21.5%) subjects had one to three abnormal primary testing. Neurocognitive dysfunction was found in 27, while prior stroke was detected in 15 (5.7%). The most frequent abnormality was elevated TCD velocity 43 (18.1%), of which five (2.1%) were in the highest velocity range of abnormal. Only impaired neurocognitive dysfunction increased with age (OR 1.44, 95%CI 1.23-1.68), p < 0.001). In univariate models, malnutrition defined as wasting (weight-for-height ≤ -2SD), but not sex or hemoglobin, was modestly related to elevated TCD (OR 1.37, 95%CI 1.01-1.86, p = 0.04). In adjusted models, neurocognitive dysfunction was strongly related to prior stroke (OR 6.88, 95%CI 1.95-24.3, p = .003) and to abnormal TCD (OR 4.37, 95%CI 1.30, p = 0.02). In a subset of 81 subjects who were enriched for other abnormal results, magnetic resonance imaging and angiography (MRI/MRA) detected infarcts and/or arterial stenosis in 52%. Thirteen subjects (25%) with abnormal imaging had no other abnormalities detected. CONCLUSIONS: The high frequency of neurocognitive impairment or other abnormal results describes a large burden of pediatric SCA brain disease in Uganda. Evaluation by any single modality would have underestimated the impact of SCA. Testing the impact of hydroxyurea or other available disease-modifying interventions for reducing or preventing SCA brain effects is warranted.

GT-WGS: an efficient and economic tool for large-scale WGS analyses based on the AWS cloud service.

BACKGROUND: Whole-genome sequencing (WGS) plays an increasingly important role in clinical practice and public health. Due to the big data size, WGS data analysis is usually compute-intensive and IO-intensive. Currently it usually takes 30 to 40 h to finish a 50× WGS analysis task, which is far from the ideal speed required by the industry. Furthermore, the high-end infrastructure required by WGS computing is costly in terms of time and money. In this paper, we aim to improve the time efficiency of WGS analysis and minimize the cost by elastic cloud computing. RESULTS: We developed a distributed system, GT-WGS, for large-scale WGS analyses utilizing the Amazon Web Services (AWS). Our system won the first prize on the Wind and Cloud challenge held by Genomics and Cloud Technology Alliance conference (GCTA) committee. The system makes full use of the dynamic pricing mechanism of AWS. We evaluate the performance of GT-WGS with a 55× WGS dataset (400GB fastq) provided by the GCTA 2017 competition. In the best case, it only took 18.4 min to finish the analysis and the AWS cost of the whole process is only 16.5 US dollars. The accuracy of GT-WGS is 99.9% consistent with that of the Genome Analysis Toolkit (GATK) best practice. We also evaluated the performance of GT-WGS performance on a real-world dataset provided by the XiangYa hospital, which consists of 5× whole-genome dataset with 500 samples, and on average GT-WGS managed to finish one 5× WGS analysis task in 2.4 min at a cost of $3.6. CONCLUSIONS: WGS is already playing an important role in guiding therapeutic intervention. However, its application is limited by the time cost and computing cost. GT-WGS excelled as an efficient and affordable WGS analyses tool to address this problem. The demo video and supplementary materials of GT-WGS can be accessed at https://github.com/Genetalks/wgs_analysis_demo .