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Introduction Home nursing and medical services have an established role in delivering chronic medical care to populations which face difficulty accessing physical clinics. Those with chronic medical conditions and reduced mobility face a higher likelihood of suffering from psychiatric co-morbidity. However, till date there has been limited research done on home-based psychiatric care in this population. Since 2021, the Psychiatry department of Tan Tock Seng Hospital (TTSH) has been collaborating with TTSH Community Health Team (CHT) to manage potential psychiatric issues in community patients. These patients would be discussed in a weekly multidisciplinary setting. If indicated, home visit by both teams for home-based assessment and treatment would be arranged, allowing for detection and treatment of psychiatric illness. Objectives To demonstrate that the collaboration between the psychiatry team and CHT leads to diagnosis and treatment of psychiatric illness in a population that might otherwise have been unable to access psychiatric services. Methods We performed a retrospective study on all referrals from the CHT to the psychiatry team, within the 2-year period of August 2021 to August 2023. We collected demographic information, psychiatric history prior to referral, reason for referral, outcome of multidisciplinary discussion, and outcome of the home visits (including diagnoses made, and medications initiated). Results A total of 92 patients were referred by the CHT to the psychiatry team. Most were elderly with multiple medical co-morbidities; of note, a history of stroke was present in 24 of the referred patients. Common reasons for referral include suspected mental illness, risk assessment, and management of behavioural issues. 28 of the referred patients did not have a prior psychiatric history at the point of referral. Among these, home visits involving the psychiatric team were done for 16 patients. 11 (68%) of these home visits led to diagnosis of a new psychiatric illness. 9 of these patients were initiated on psychotropic medications in the home setting. Conclusions A significant proportion of patients (68% of home visits without prior psychiatric diagnosis) were newly diagnosed with psychiatric illness, allowing early psychiatric intervention to be delivered. This was achieved in a population with a high prevalence of multiple medical comorbidity and barriers to clinic-based psychiatric evaluation and treatment. We propose future comparative studies into how the collaboration between the psychiatric team and community health team can improve the quality of life and caregiver experience of patients with chronic medical problems, as well as how the service had improved the confidence of the community health team in identifying and managing patients with possible psychiatric issues. Disclosure of Interest None Declared

Abstract Summary Cardiometabolic diseases are associated with low-grade inflammation early in life and persists into old age. The long latency period presents opportunities for early detection, lifestyle modification and intervention. However, the performance of conventional biomarker assays to detect low-grade inflammation has been variable, particularly for early-stage cardiometabolic disorder including prediabetes and subclinical atherosclerotic vascular inflammation. During the last decade, the application of nuclear magnetic resonance (NMR) spectroscopy for metabolic profiling of biofluids in translational and epidemiological research has advanced to a stage approaching clinical application. Proton (1H)-NMR profiling induces no destructible physical changes to specimens, and generates quantitative signals from deconvoluted spectra that are highly repeatable and reproducible. Apart from quantitative analysis of amino acids, lipids/lipoproteins, metabolic intermediates and small proteins, 1H-NMR technology is unique in being able to detect composite signals of acute-phase and low-grade inflammation indicated by glycosylated acetyls (GlycA) and N-acetylneuraminic acid (sialic acid) moieties (GlycB). Different from conventional immunoassays that target epitopes and are susceptible to conformational variation in protein structure and binding, GlycA and GlycB signals are stable over time, and maybe complementary as well as superior to high-sensitivity C-reactive protein and other inflammatory cytokines. Here we review the physicochemical principles behind 1H-NMR profiling of GlycA and GlycB, and the available evidence supporting their potential clinical application for the prediction of incident (pre)diabetes, cardiovascular disease, and adverse outcomes.

BackgroundSurgery is an indispensable component of a functional healthcare system. To date there is limited information regarding how many people die during the perioperative period globally. This study describes a protocol for a systematic review and multilevel meta-regression to evaluate time trends regarding the odds of perioperative mortality among adults undergoing a bellwether surgical procedure while accounting for higher order clustering at the national level.MethodsPublished studies reporting the number of perioperative deaths from bellwether surgical procedures among adults will be identified from MEDLINE, Embase, Cochrane CENTRAL, LILACS and Global Index Medicus. The primary outcome will be the rate of perioperative mortality across time and the secondary outcome will be investigating cause of death over time as a proportion of overall perioperative mortality. Two reviewers will independently conduct full text screening and extract the data. Disagreements will first be resolved via consensus. If consensus cannot be reached a third reviewer will be included to arbitrate. Due to human resource limitations, a risk of bias appraisal will not be conducted. From the included studies a multilevel meta-regression will be constructed to synthesize the results. This model will conceptualize patients as nested in studies which are in turn nested within countries while taking into account potential confounding variables at all levels.DiscussionThe systematic review and multilevel meta-regression that will be conducted based on this protocol will provide synthesized global evidence regarding the trends of perioperative mortality. This eventual study may help policymakers and other key stakeholders with benchmarking surgical safety initiatives as well as identify key gaps in our current understanding of global perioperative mortality.Trial registrationSystematic review registration: PROSPERO registration number 429040.

Engineers often play vital roles in technical planning, designing, and operating projects, as well as implementing standard requirements in the physical sites. Although architectural designs may be similar in a construction project, the technical problems, including soil conditions, loading calculations, team combination, etc., often vary between projects. Although previous studies focus on the stress management of construction professionals, little research has been particularly conducted for the effects of stressors and stress of engineers on their organizational commitment. It is inevitable for engineers to experience different uncertainties, harsh working environments, and serious legal liabilities, while there is often no tolerance when it comes to deadlines and safety requirements. All this definitely puts great pressure on them and may subsequently affect their commitment to their organizations. The present study aimed to investigate the impact of stressors and stress on the commitment of engineers in the construction industry. A total of 146 respondents participated in a questionnaire survey, and various statistical analyses including a reliability test, correlation, and hierarchical multiple regressions were adopted for developing the optimized commitment models. The research results revealed that (1) Type A personality was a key factor, which had a significant positive effect on all the three organizational commitments of professional engineers in the construction industry; (2) poor office environment, job overload, and role ambiguity were positively associated with continuance and normative commitment, whereas poor site environment and lack of job autonomy were negatively linked with affective commitment; and (3) stress had a negative relationship with affective commitment; (4) however, there was no relationship between stress and continuance or normative commitment. In order to establish holistic organizational commitment strategies in the industry well, the current study indicates key stressors to upper management to help them efficiently manage complicated project teams in construction projects. In addition, it contributes the body of knowledge by developing an integrated commitment model for engineers. Finally, numerous recommendations are made, such as encouraging Type A personality behaviors, providing sufficient job autonomy, improving worksite conditions to enhance the organizational commitment of engineers, and reducing the adverse impacts of these stressors and stress.

BackgroundDuring slow pathway modification for atrioventricular nodal reentrant tachycardia, heart block may occur if ablation cannot be stopped in time in response to high risk electrogram features (HREF).ObjectivesTo develop an automatic algorithm to monitor HREF and terminate ablation earlier than human reaction.MethodsDigital electrogram data from 332 ablation runs from February 2020 to June 2022 were included. They were divided into training and validation sets which contained 126 and 206 ablation runs respectively. HREF in training set was measured. Then a program was developed with cutoff values decided from training set to capture all these HREF. Simulation ablation videos were rendered using validation set electrogram data. The videos were played to three independent electrophysiologists who each determined when to stop ablation. Timing of ablation termination, sensitivity, and specificity were compared between human and program.ResultsReasons for ablation termination in the training set include short AA time, short VV time, AV block and VA block. Cutoffs for the program were set to maximize program sensitivity. Sensitivity and specificity for the program in the validation set were 95.2% and 91.1% respectively, which were comparable to that of human performance at 93.5% and 95.4%. If HREF were recognized by both human and program, ablations were terminated earlier by the program 90.2% of times, by a median of 574 ms (interquartile range 412–807 ms, p

Objectives To quantify the burden of death that COVID-19 contributes relative to the top three causes of death for all countries.Design We performed uncertainty analyses and created contour plots for COVID-19 mortality to place the number of COVID-19 deaths in context relative to the top three causes of death in each country, across a plausible range of values for two key parameters: case fatality rate and magnitude of under-reporting.Setting All countries that have reported COVID-19 cases to the WHO and are included in the Global Burden of Disease Study by the Institute of Health Metrics and Evaluation.Main outcomes and measures Monthly number of deaths caused by COVID-19 and monthly number of deaths caused by the top three causes of death for every country.Results For countries that were particularly hard hit during the outbreak in 2020, most combinations of model parameters resulted in COVID-19 ranking within the top three causes of death. For countries not as hard hit on a per-capita basis, such as China and India, COVID-19 did not rank higher than the third leading cause of death at any combination of the model parameters within the given ranges. Up-to-date ranking of COVID-19 deaths relative to the top three causes of death for all countries globally is provided in an interactive online application.Conclusions Estimating the country-level burden of death that COVID-19 contributes relative to the top three causes of death is feasible through contour graphs, even when the actual number of deaths or cases is unknown. This method can help convey importance by placing the magnitude of COVID-related deaths in context relative to more familiar causes of death by communicating when COVID-related deaths rank among the top three causes of death.

Abstract Background Contemporary data of peripheral T‐cell lymphoma (PTCL) and natural‐killer/T‐cell lymphoma (NKTL) patients treated with ifosfamide, carboplatin and etoposide (ICE) are limited. Aims We performed a retrospective analysis to estimate outcomes of ICE‐treated PTCL and NKTL patients at three tertiary cancer centres in Singapore. Methods and Results Patients were identified through lymphoma databases from National Cancer Centre Singapore (NCCS), National University Hospital, Singapore (NUHS), and Singapore General Hospital (SGH). Responses and survival outcomes were determined from electronic medical records. A total of 75 patients with a median age of 50 were included. ICE was used as first‐line treatment in 14 patients (19%) and as subsequent lines of treatment in 61 patients (81%). The overall response rates (ORR) for all patients was 63% (40% complete response [CR]). The ORR and CR in the first line were 86% and 64% respectively. At a median follow‐up duration of 71.0 months, the median progression‐free (PFS) and overall survival (OS) for all patients were 4.4 months (95%CI, 2.7–6.0) and 16 months (95%CI, 8.3–45.4) respectively. Conclusion In summary, ICE showed high ORR but poor PFS in relapsed/refractory PTCL and NKTL. ORR of ICE in the first line setting appears better than real‐world CHOP data and warrants further study.

Wireless accelerometers with various operating ranges have been used to measure tibial acceleration. Accelerometers with a low operating range output distorted signals and have been found to result in inaccurate measurements of peaks. A restoration algorithm using spline interpolation has been proposed to restore the distorted signal. This algorithm has been validated for axial peaks within the range of 15.0–15.9 g. However, the accuracy of peaks of higher magnitude and the resultant peaks have not been reported. The purpose of the present study is to evaluate the measurement agreement of the restored peaks using a low-range accelerometer (±16 g) against peaks sampled using a high-range accelerometer (±200 g). The measurement agreement of both the axial and resultant peaks were examined. In total, 24 runners were equipped with 2 tri-axial accelerometers at their tibia and completed an outdoor running assessment. The accelerometer with an operating range of ±200 g was used as reference. The results of this study showed an average difference of −1.40 ± 4.52 g and −1.23 ± 5.48 g for axial and resultant peaks. Based on our findings, the restoration algorithm could skew data and potentially lead to incorrect conclusions if used without caution.

Due to the inherent limitations of underground spaces, such as the lack of natural ventilation and sunlight, underground space users tend to face more health risks compared with their aboveground counterparts. However, little is known about how the underground environment, users’ health, and their associations were impacted by the outbreak of the pandemic. In this study, we investigated and compared the impacts of the general underground environment on regular users’ physical and psychological health before and after the pandemic. To achieve this aim, the data from 525 surveys were collected from eleven underground sites, followed by an objective field measurement study conducted at five underground sites in Hong Kong pre- and post-outbreak of the pandemic. The multigroup structural equation modelling results indicated that: (i) surprisingly, the users’ satisfaction towards almost all underground environment factors, including greenery, connectivity with the aboveground environment, thermal comfort, ventilation, indoor air quality, acoustic comfort, and lighting, excluding wayfinding, were significantly higher in the post-outbreak period; (ii) the users’ health, both physical and psychological, was significantly better in the post-outbreak period; (iii) the impacts of visual comfort on the users’ physical and psychological health were significantly greater in the post-outbreak period (critical difference ratio (|CDR|) > 1.96); (iv) the impacts of wayfinding, greenery, and acoustic and thermal comfort on the users’ physical or psychological health were significant only in the pre-outbreak period (|CDR| > 1.96); (v) the impacts of connectivity on the users’ physical and psychological health were significant in both the pre- and post-outbreak periods (|CDR| < 1.96). The findings were further cross-validated using the objective measurement results. With an increasing need to develop healthy underground spaces, the study contributes to the development, design, and management of the underground environment to enhance the users’ health in the post-outbreak era.

Motor commands for human locomotion are generated by combination of muscle synergies. In humans, muscle synergies for running exhibit considerable plasticity during child-to-adult development and adult training to meet the constantly changing biomechanical and efficiency demands.

The COVID-19 pandemic caused widespread disruption to many individuals' lifestyles. Social distancing restrictions implemented during this global pandemic may bring potential impact on physical activity habits of the general population. However, running is one of the most popular forms of physical activity worldwide and one in which it could be maintained even during most COVID-19 restrictions. We aimed to determine the impact of COVID-19 restrictions on runners' training habits through analyzing the training records obtained from their GPS enabled wearable trackers. Retrospective and prospective data were collected from an online database (https://wetrac.ucalgary.ca). Runners' training habits, including frequency, intensity and duration of training, weekly mileage and running locations were analyzed and compared 9 months before and after the start of COVID-19 restrictions in March 2020. We found that runners ran 3 km per week more (p = 0.05, Cohen's d = 0.12) after the start of COVID-19 restrictions, and added 0.3 training sessions per week (p = 0.03, Cohen's d = 0.14). Moreover, runners ran an additional 0.4 sessions outdoors (p < 0.01, Cohen's d = 0.21) but there was no significant change in the intensity or duration of training sessions. Our findings suggested that runners adopted slightly different training regimen as a result of COVID-19 restrictions. Our results described the collective changes, irrespective of differences in response measures adopted by various countries or cities during the COVID-19 pandemic.

This paper quantifies the net impact (direct and indirect effects) of the pandemic on the United States population in 2020 using three metrics: excess deaths, life expectancy, and total years of life lost. The findings indicate there were 375,235 excess deaths, with 83% attributable to direct, and 17% attributable to indirect effects of COVID-19. The decrease in life expectancy was 1.67 years, translating to a reversion of 14 years in historical life expectancy gains. Total years of life lost in 2020 was 7,362,555 across the USA (73% directly attributable, 27% indirectly attributable to COVID-19), with considerable heterogeneity at the individual state level.

Fabry Disease (FD) is a systemic disorder that can result in cardiovascular, renal, and neurovascular disease leading to reduced life expectancy. FD should be considered in the differential of all patients with unexplained left ventricular hypertrophy (LVH). We therefore performed a prospective screening study in Edmonton and Hong Kong using Dried Blood Spot (DBS) testing on patients with undiagnosed LVH. Participants found to have unexplained LVH on echocardiography were invited to participate and subsequently subjected to DBS testing. DBS testing was used to measure α-galactosidase (α-GAL) enzyme activity and for mutation analysis of the α-galactosidase (GLA) gene, both of which are required to make a diagnosis of FD. DBS testing was performed as a screening tool on patients (n = 266) in Edmonton and Hong Kong, allowing for detection of five patients with FD (2% prevalence of FD) and one patient with hydroxychloroquine-induced phenocopy. Left ventricular mass index (LVMI) by GLA genotype showed a higher LVMI in patients with IVS4 + 919G > A mutations compared to those without the mutation. Two patients were initiated on ERT and hydroxychloroquine was discontinued in the patient with a phenocopy of FD. Overall, we detected FD in 2% of our screening cohort using DBS testing as an effective and easy to administer screening tool in patients with unexplained LVH. Utilizing DBS testing to screen for FD in patients with otherwise undiagnosed LVH is clinically important due to the availability of effective therapies and the value of cascade screening in extended families.

BackgroundPreterm birth is the leading cause of neonatal and child mortality worldwide. Maternal HIV infection and antiretroviral treatment (ART) increase the rate of preterm birth, but the underlying mechanisms remain unknown, limiting progress in prediction, prevention and treatment. While overall γδ T cell levels remain constant, acute HIV infection is associated with a depletion of the Vδ2 subset and an increase in the Vδ1 subset, which do not return to baseline with ART. γδ T cells have also been implicated in adverse pregnancy outcomes and we therefore investigated the potential association between maternal HIV infection, peripheral γδ T cell frequencies and preterm birth.MethodsStudy participants were HIV positive (n = 47) and HIV negative (n = 45) women enrolled in a prospective pregnancy cohort study at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. Women were enrolled in early pregnancy and gestational age was accurately determined by first trimester ultrasound scan. Peripheral blood samples were collected in each trimester and peripheral blood mononuclear cells isolated. Frequencies of γδ T cells, Vδ1+ and Vδ2+ γδ T cell subsets, and CCR6 chemokine receptor expression were determined by flow cytometry.ResultsTotal γδ T cell levels were similar between HIV positive and HIV negative women throughout pregnancy. However, in each trimester maternal HIV infection was associated with reduced levels of the Vδ2+ subset and increased levels of the Vδ1+ subset, leading to a reversal of the Vδ1/Vδ2 ratio. Timing of ART initiation among HIV positive women did not affect levels of γδ T cells, the Vδ1+ and Vδ2+ subsets, or the Vδ1/Vδ2 ratio. Importantly, preterm birth was associated with lower total γδ T cell levels in early pregnancy and γδ T cell frequencies were lowest in HIV positive women who delivered preterm. Moreover, in the first trimester the proportion of Vδ1+ T cells that were CCR6+ was significantly reduced in HIV+ women and women who delivered preterm, resulting in the lowest proportion of CCR6+ Vδ1 T cells in HIV positive women who delivered preterm.ConclusionsOur findings suggest that altered γδ T cell frequencies may link maternal HIV infection and preterm birth. γδ T cell frequencies in early pregnancy may serve as predictive biomarkers to identify women at risk of delivering preterm.

The present study compared the effect between walking exercise and a newly developed sensor-based gait retraining on the peaks of knee adduction moment (KAM), knee adduction angular impulse (KAAI), knee flexion moment (KFM) and symptoms and functions in patients with early medial knee osteoarthritis (OA). Eligible participants (n = 71) with early medial knee OA (Kellgren-Lawrence grade I or II) were randomized to either walking exercise or gait retraining group. Knee loading-related parameters including KAM, KAAI and KFM were measured before and after 6-week gait retraining. We also examined clinical outcomes including visual analog pain scale (VASP) and Knee Injury and Osteoarthritis Outcome Score (KOOS) at each time point. After gait retraining, KAM1 and VASP were significantly reduced (both Ps < 0.001) and KOOS significantly improved (p = 0.004) in the gait retraining group, while these parameters remained similar in the walking exercise group (Ps ≥ 0.448). However, KAM2, KAAI and KFM did not change in both groups across time (Ps ≥ 0.120). A six-week sensor-based gait retraining, compared with walking exercise, was an effective intervention to lower medial knee loading, relieve knee pain and improve symptoms for patients with early medial knee OA.

What was once a science fiction fantasy, virtual reality (VR) technology has evolved and come a long way. Together with augmented reality (AR) technology, these simulations of an alternative environment have been incorporated into rehabilitation treatments. The introduction of head-mounted displays has made VR/AR devices more intuitive and compact, and no longer limited to upper-limb rehabilitation. However, there is still limited evidence supporting the use of VR and AR technology during locomotion, especially regarding the safety and efficacy relating to walking biomechanics. Therefore, the objective of this study is to explore the limitations of such technology through gait analysis. In this study, thirteen participants walked on a treadmill in normal, virtual and augmented versions of the laboratory environment. A series of spatiotemporal parameters and lower-limb joint angles were compared between conditions. The center of pressure (CoP) ellipse area (95% confidence ellipse) was significantly different between conditions (p = 0.002). Pairwise comparisons indicated a significantly greater CoP ellipse area for both the AR (p = 0.002) and VR (p = 0.005) conditions when compared to the normal laboratory condition. Furthermore, there was a significant difference in stride length (p0.082), except for maximum ankle plantarflexion (p = 0.001). These differences in CoP ellipse area indicate that users of head-mounted VR/AR devices had difficulty maintaining a stable position on the treadmill. Also, differences in the gait parameters suggest that users walked with an unusual gait pattern which could potentially affect the effectiveness of gait rehabilitation treatments. Based on these results, position guidance in the form of feedback and the use of specialized treadmills should be considered when using head-mounted VR/AR devices.

This study introduced a novel but simple method to continuously measure footstrike patterns in runners using inexpensive force sensors. Two force sensing resistors were firmly affixed at the heel and second toe of both insoles to collect the time signal of foot contact. A total of 109 healthy young adults (42 males and 67 females) were recruited in this study. They ran on an instrumented treadmill at 0°, +10°, and -10° inclinations and attempted rearfoot, midfoot, and forefoot landings using real time visual biofeedback. Intra-step strike index and onset time difference between two force sensors were measured and analyzed with univariate linear regression. We analyzed 25,655 footfalls and found that onset time difference between two sensors explained 80-84% of variation in the prediction model of strike index (R-squared = 0.799-0.836, p

Quantitative methods were established to determine the level of maturation of human embryonic stem cell-derived ventricular cardiomyocytes (hESC-vCMs) that were treated with different metabolic stimulants (i.e., isoproterenol and oleic acid) during early differentiation. Cells were double-immunolabeled with α-actinin and COX IV antibodies, to label the myofibrils and mitochondria, respectively, after which images were acquired via confocal microscopy. In order to determine the extent of differentiation, image analysis protocols were then used to quantify cell shape and area, as well as the degree of myofibrillar organization and intercalation of mitochondria between the myofibrils within the cells. We demonstrated that oleic acid or isoproterenol alone, or a combination of the two, induced a more elongated hESC-vCM phenotype than the untreated controls. In addition, cells treated with isoproterenol alone exhibited a similar level of myofibrillar organization as the controls, but those treated with oleic acid with/without isoproterenol exhibited a more organized (parallel) orientation of myofibrils. The combined isoproterenol/oleic acid treatment also resulted in enhanced intercalation of mitochondria between the myofibrils. We suggest that these quantitative morphometric methods might serve as simple and effective tools that can be utilized in the determination of the level of structural maturation of hESC-vCMs.

OBJECTIVE: To study the attitudes among general practitioners towards pneumococcal vaccination for middle-aged (50-64) and elderly population (over 65) in Hong Kong and the factors affecting their decision to advise pneumococcal vaccination for those age groups. DESIGN: Cross-sectional study of general practitioners in private practice in Hong Kong. PARTICIPANTS: Members of Hong Kong Medical Association delivering general practice services in private sector. MEASURING TOOL: Self-administered questionnaire. MAIN OUTCOME MEASURES: Intention to recommend pneumococcal vaccination, barriers against pneumococcal vaccination. RESULTS: 53.4% of the respondents would actively recommend pneumococcal vaccination to elderly patients but only 18.8% would recommend for middle-aged patients. Consultation not related to pneumococcal vaccine was the main reason for not recommending pneumococcal vaccine (43.6%). Rarity of pneumonia in their daily practice was another reason with 68.4% of respondents attending five or less patients with pneumonia each year. In multivariate analysis, factors such as respondents would get vaccination when reaching age 50 (ORm 10.1), and attending 6 pneumonia cases or more per year (ORm 2.28) were found to be associated with increasing likelihood for recommending vaccination to the middle-aged. While concerns of marketing a product (ORm 0.41), consultation not related to vaccination (ORm 0.45) and limited time (ORm 0.38) were factors that reduced the likelihood. CONCLUSION: Public policy is needed to increase the awareness of impact of pneumococcal pneumonia and the availability of preventive measures.

Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.