Quality control metrics improve repeatability and reproducibility of single-nucleotide variants derived from whole-genome sequencing.

Although many quality control (QC) methods have been developed to improve the quality of single-nucleotide variants (SNVs) in SNV-calling, QC methods for use subsequent to single-nucleotide polymorphism-calling have not been reported. We developed five QC metrics to improve the quality of SNVs using the whole-genome-sequencing data of a monozygotic twin pair from the Korean Personal Genome Project. The QC metrics improved both repeatability between the monozygotic twin pair and reproducibility between SNV-calling pipelines. We demonstrated the QC metrics improve reproducibility of SNVs derived from not only whole-genome-sequencing data but also whole-exome-sequencing data. The QC metrics are calculated based on the reference genome used in the alignment without accessing the raw and intermediate data or knowing the SNV-calling details. Therefore, the QC metrics can be easily adopted in downstream association analysis.

Material versatility using replica molding for large-scale fabrication of high aspect-ratio, high density arrays of nano-pillars.

Arrays of high aspect-ratio (AR) nano-pillars have attracted a lot of interest for various applications, such as for use in solar cells, surface acoustic sensors, tissue engineering, bio-inspired adhesives and anti-reflective surfaces. Each application may require a different structural material, which can vary in the required chemical composition and mechanical properties. In this paper, a low cost fabrication procedure is proposed for large scale, high AR and high density arrays of nano-pillars. The proposed method enables the replication of a master with high fidelity, using the subsequent replica molds multiple times, and preparing arrays of nano-pillars in a variety of different materials. As an example applied to bio-inspired dry adhesion, polymeric arrays of nano-pillars are prepared in this work. Thermoset and thermoplastic nano-pillar arrays are examined using an atomic force microscope to assess their adhesion strength and its uniformity. Results indicate the proposed method is robust and can be used to reliably prepare nano-structures with a high AR.

Emergency department presentation of ketamine abusers in Hong Kong: a review of 233 cases.

OBJECTIVES: To study the acute clinical presentations of ketamine abusers in Hong Kong. DESIGN: Retrospective chart review. SETTING: Fifteen accident and emergency departments in Hong Kong. PATIENTS: Consultations associated with recent ketamine use either confirmed by history or urine test were searched for from the database of the Hospital Authority Hong Kong Poison Information Centre from 1 July 2005 to 30 June 2008. Their medical records and investigation results were analysed. RESULTS: A total of 233 records of ketamine use were included for review. Patient ages ranged from 13 to 60, with a median of 22 years, and the male-to-female ratio being 2.1:1. The most common symptoms of ketamine misuse were impaired consciousness (45%), abdominal pain (21%), lower urinary tract symptoms (12%), and dizziness (12%). The most common abnormal physical findings were high blood pressure (40%), followed by tachycardia (39%), abdominal tenderness (18%), and white powder in the nostrils (17%). CONCLUSION: Most ketamine abusers presented acutely with transient central nervous system depression, abdominal pain, or lower urinary tract symptoms. Clinicians should be alert to the typical age-group, signs and symptoms of such abusers presenting in an acute medical setting.

First cervical vertebra (atlas) fracture mechanism studies using finite element method.

Injury mechanisms and stress distribution patterns are important in the clinical evaluation of spinal injuries. Recognition and interpretation of the failure patterns help to determine spinal instability and consequently the choice of treatment. Although, the biomechanics responses of the atlas have received much attention, it has not been investigated using theoretical modeling. Mathematical techniques such as finite element model will provide further understanding to the injury mechanisms of the atlas, which is important for the prevention, diagnosis, and treatment of spinal injuries. In the present study, a detailed three-dimensional finite element model of the human atlas (C1) was constructed, with the geometrical data obtained using a three-dimensional digitizer. Anterior arch, superior/inferior articular processes, transverse processes, posterior arch and posterior tubercule were modeled using eight-noded brick elements. Using the material properties from literature, the 7808-finite element model was exercised under three simulated axial compressive mode of pressure loading and boundary conditions to investigate the sites of failure reported in vivo and in vitro. This report demonstrates high concentration of localized stress at the anterior and posterior archs of the atlas, which agrees well with those reported in the literature. Furthermore, under simulated hyperextension, our results agreed well with the experimental findings, which show that the groove of the posterior arch is subjected to enormous bending moment. The close agreement of the failure location provided confidence to perform further analysis and in vitro experiments. These results may be potentially used to supplement experimental research in understanding the clinical biomechanics of the atlas.

Statistical factorial analysis on the material property sensitivity of the mechanical responses of the C4-C6 under compression, anterior and posterior shear.

A systematic approach using factorial analysis was conducted on the C4-C6 finite element model to analyse the influence of six spinal components (cortical shell, vertebral body, posterior elements, endplate, disc annulus and disc nucleus) on the internal stresses and external biomechanical responses under compression, anterior and posterior shear. Results indicated that the material properties variation of the disc annulus has a significant influence on both the external biomechanical responses and internal stress of the disc annulus and its neighboring hard bones. The study reveals for the first time, the significant influence of the cancellous bone under compression, while variation in the cortical shell modulus has a high influence under anterior and posterior shear. The study also reveals that the effects of interaction between two main components are insignificant.

Experimental investigation of failure load and fracture patterns of C2 (axis).

The injury mechanism and magnitude of failure load of C2 fractures are important in the clinical treatment of its fixation. The magnitudes of the failure load of C2 and the mechanism of injury in vivo are uncertain. Accordingly, nine C2 vertebrae obtained from cadaver spines, ranging in age from 51 to 80 years, were used for the study. Special restraint conditions were applied to yield specific fracture of C2. With the posterior element potted postero-anteriorly up to one-quarter of the inferior facet, posterior shear force ranging from 840 to 1220N was required to cause fracture across the pars interarticularis. For odontoid fracture study, a special rig was fabricated to encapsulate the body of C2 in a cell using ISOPON, and a thin layer of ISOPON sandwiched between the inferior facets and two lateral plates. The assembled rig permits slight sagittal movement of C2 about the cup lateral pivot supports. Failure load of between 900 and 1500N was recorded for odontoid fracture. These values are in agreement with published data. The experiment carried out under these two different restraint conditions had specifically resulted in different fractures of C2. In reality, depending on factors such as the inclination of this force vector applied to the head, the precise posture at the time of trauma, the spinal geometry, and the physical properties, different types of fracture patterns of C2 may be produced. This additional data will be useful in the biomechanical study of C2 vertebra using analytical approaches, and in surgical anterior/posterior fixation using screws.

The biomechanics of lumbar graded facetectomy under anterior-shear load.

In this paper, an anatomically accurate three-dimensional finite-element (FE) model of the human lumbar spine (L2-L3) was used to study the biomechanical effects of graded bilateral and unilateral facetectomies of L3 under anterior shear. The intact L2-L3 FE model was validated under compression, tension, and shear loading and the predicted responses matched well with experimental data. The gross external (translational and coupled) responses, flexibilities, and facet load were delineated for these iatrogenic changes. Results indicted that unilateral facetectomy of greater than 75% and bilateral facetectomy of 75% or more resection markedly alter the translational displacement and flexibilities of the motion segment. This study suggests that fixation or fusion to restore strength and stability of the lumbar spine may be required for surgical intervention of greater than 75% facetectomy.

Finite-element analysis for lumbar interbody fusion under axial loading.

A parametric study was conducted to evaluate axial stiffness of the interbody fusion, compressive stress, and bulging in the endplate due to changes in the spacer position with/without fusion bone using an anatomically accurate and validated L2-L3 finite-element model exercised under physiological axial compression. The results show that the spacer plays an important role in initial stability for fusion, and high compressive force is predicted at the ventral endplate for the models with the spacer and fusion bone together. By varying the positioning of the spacer anteriorly along anteroposterior axis, no significant change in terms of axial stiffness, compressive stress, and bulging of the endplate are predicted for the implant model. The findings suggest that varying the spacer position in surgical situations does not affect the mechanical behavior of the lumbar spine after interbody fusion.

Evaluation of the role of ligaments, facets and disc nucleus in lower cervical spine under compression and sagittal moments using finite element method.

Cervical spinal instability due to ligamentous injury, degenerated disc and facetectomy is a subject of great controversy. There is no analytical investigation reported on the biomechanical response of cervical spine in these respects. Parametric study on the roles of ligaments, facets, and disc nucleus of human lower cervical spine (C4-C6) was conducted for the very first time using noninvasive finite element method.A three-dimensional (3D) finite element (FE) model of the human lower cervical spine, consisted of 11,187 nodes and 7730 elements modeling the bony vertebrae, articulating facets, intervertebral disc, and associated ligaments, was developed and validated against the published data under three load configurations: axial compression; flexion; and extension. The FE model was further modified accordingly to investigate the role of disc, facets and ligaments in preserving cervical spine motion segment stability in these load configurations. The passive FE model predicted the nonlinear force displacement response of the human cervical spine, with increasing stiffness at higher loads. It also predicted that ligaments, facets or disc nucleus are crucial to maintain the cervical spine stability, in terms of sagittal rotational movement or redistribution of load. FE method of analysis is an invaluable application that can supplement experimental research in understanding the clinical biomechanics of the human cervical spine.

Comparison of bioimpedance and Doppler ultrasound cardiac output in CAPD patients.

The reproducibility and reliability of cardiac output (CO) measurement by transthoracic electrical bioimpedance (TEB) and dual beam Doppler ultrasound methods were compared in 9 uremic patients during treatment with continuous ambulatory peritoneal dialysis (CAPD). CO was measured simultaneously by each method during supine rest and 70 degree passive head-up tilt on two separate days. The effect on CO after the infusion of dialysate was also studied on day 1. CO, stroke volume (SV) and heart rate (HR) measurements were reproducible by each method. The median day to day differences (95% confidence intervals) in CO and SV were 0.6 (-0.3, 1.8) l/min and 10 (-1.5, 24.5) ml for TEB and 0.7 (-0.5, 2.2) l/min and 13 (-1.0, 30.5) ml for Doppler at supine rest; 0.4 (-0.2, 0.9) l/min and 11 (-0.5, 19.0) ml for TEB and 0.5 (-0.3, 1.2) l/min and 8 (-5.0, 16.0) ml for Doppler during tilt (p > 0.05 in each case). Data were unobtainable by TEB at five time points while none were lost by Doppler. This is due to incorrect HR or poor quality signals detected by TEB. CO and SV measured by Doppler were higher than that by TEB during supine rest (p < or = 0.01) but not during passive tilt. As a result, there was significant change (p < or = 0.01) in CO and SV from supine to tilt measured by Doppler but not by TEB. Neither TEB nor Doppler detected significant change (p > 0.05) in CO or SV after the infusion of dialysate, in either the supine or tilt positions.(ABSTRACT TRUNCATED AT 250 WORDS)

An axisymmetric contact model of ultra high molecular weight polyethylene cups against metallic femoral heads for artificial hip joint replacements.

Contact mechanics of ultra high molecular weight polyethylene (UHMWPE) cups against metallic femoral heads for artificial hip joints is considered in this study. Both the experimental measurement of the contact area and the finite element prediction of the contact radius, maximum contact pressure and maximum Von Mises stress have been carried out for a wide range of contemporary artificial hip joints. Good agreement of the contact radius has been found between the experimental measurements and the finite element predictions based upon an elastic modulus of 1000 MPa and a Poisson's ratio of 0.4 for UHMWPE material under various loads up to 2.5 kN. It has been shown that the half contact angle for all the cup/head combinations considered in this study is between 40 degrees and 50 degrees under a load of 2.5 kN. The importance of this result has been discussed with respect to the anatomical position of the cup when placed in the body and the selection of a simple wear-screening test for artificial hip joints. The predicted contact radius and maximum contact pressure from the finite element model have also been compared with a simple elasticity analysis. It has been shown that the difference in the predicted contact radius between the two methods is reduced for more conforming contacts between the femoral head and the acetabular cup and smaller UHMWPE cup thickness. However, good agreement of the predicted maximum contact pressure has been found for all the combinations of the femoral head and the acetabular cup considered in this study. The importance of contact mechanics on the clinical performance of artificial hip joint replacements has also been discussed.

A study of the P blood group system in the Singaporean population.

The P blood-group system was discovered by Landsteiner and Levine in 1927. This study delineates: a) The ethnic group specific distribution patterns of the P1 blood group antigen in the population of Singapore. b) The occurrence rate of the anti-P1 antibody in the same population. In the blood donor population, the estimated incidence of the P1-negative phenotype was calculated to be 75%. Though the percentage of P1-negative individuals among the Chinese did not differ significantly from that for the Malays, it was significantly higher than that for the Indians (P less than 0.01). The weighted average incidence of anti-P1 in the blood-donor population over the period 1982-1987 was calculated to be 9.14 per 100,000. For the patients, the average incidence of the anti-P1 antibody was calculated to be about 13.9 per 100,000 patients. The Malays were noted to have the highest incidence of anti-P1 antibody despite the occurrence of a higher proportion of P1-negatives among the Chinese.

Chronic myeloid leukaemia in Singapore: a case study of 56 patients.

A case study was made on 56 patients with chronic myeloid leukaemia in Singapore. The most common clinical presentations were abdominal discomfort with swelling and hepatosplenomegaly. The mean haemoglobin, white cell count, and platelet count at presentation were 9.23 g/dl, 217.9 X 10(9)/1 and 418 X 10(9)/1 respectively. Twenty-three of the 56 patients had gone into blast transformation at the time of analysis. The median duration of the chronic phase from the time of diagnosis to the time of blast transformation was 23 months. The median duration of survival after blast transformation was 3 months. The median duration of survival for all patients was 23 months. Busulphan remains the drug of choice for the chronic phase of chronic myeloid leukaemia.

Immunological typing of acute lymphoblastic leukaemia patients in Singapore--a preliminary experience.

Six new patients with acute lymphoblastic leukaemia (ALL) have been studied with a battery of cell surface marker assays. These included T cell enumeration, B cell enumeration, monoclonal antibody studies for T cell subsets, (T helper cells, T suppressor cells and mature peripheral total T cells), HLA--DR (Ia-like antigens) and common ALL antigen. Three patients were found to have common ALL, 2 had null cell ALL and one had T cell ALL. Cytochemical studies on these 6 patients demonstrated a positive correlation between E rosette positivity and focal paranuclear staining with acid phosphatase. There appeared to be no correlation between FAB morphology and immunological subtype in the 6 patients studied.

Liver dysfunction in haemophilia A, B and other hereditary haemorrhagic disorders.

Seventy patients with Haemophilia A, B, von Willebrand's disease and Factor V deficiency had their liver functions studied. Twenty-five patients (36%) were found to have significant "transaminitis" (elevated SGPT/SGOT). Nine patients (13%) had positive Hepatitis B surface antigen (HBsAg). The incidence of Hepatitis B surface antibody (anti-HBs) in the study group was 74%. All patients were asymptomatic at the time of study. This asymptomatic liver dysfunction will require close monitoring for clinical significance.

Analytical static stress analysis of first cervical vertebra (atlas).

INTRODUCTION: Fracture of the atlas was first described by Jefferson (1920). He theorised a bursting mechanism of fracture as the occipital condyles were driven into the atlas. Experimental studies by Hays and Alker (1988) and Panjabi et al (1991) were also conducted to explain the injury mechanisms. Injury mechanisms and fracture patterns are important in the clinical evaluation of spinal injuries. Recognition and interpretation of the fracture patterns help to determine the spinal instability and consequently the choice of treatment. Although the fracture mechanics of the atlas have received much attention, it has not been investigated using theoretical modelling. MATERIALS AND METHODS: A high-definition digitiser was used to obtain the geometrical data for the finite element mesh generation. Contrary to the widely used method, such as computed tomography scan for geometric extraction, the direct digitising process of the dried specimen reliably preserves the accurate topography of up to 0.1-mm interval of the original structure. The finite element model was exercised under an axial compressive mode of pressure loading to investigate the sites of failure reported in vivo and in vitro. RESULTS: Using material properties from literature, the predicted results from the 7808-finite element model demonstrate high concentration of localised stress at the anterior and posterior arch of the atlas, which agrees well with those reported in the literature. Furthermore, our results are also in good agreement with the findings reported by Panjabi et al (1991), which show that the groove of the posterior arch is subjected to enormous bending moment under simulated hyperextension conditions. CONCLUSIONS: The close agreement of the failure location provided confidence to perform further analysis and in vitro experiments. The predicted results from finite element analysis may be potentially used to supplement experimental research in understanding the clinical biomechanics of the C1.

An analysis of blood usage in elective surgery.

Pre-operative blood requests are often greatly in excess of the number of units of blood actually transfused during elective surgical procedures. Such practices are costly in terms of laboratory manpower and leads to unnecessary wastage of blood due to outdating. Developing guidelines for the number of blood units to cross-match preoperatively for surgical procedures optimises the use of blood. This study reports on blood ordering patterns and offers guidelines on the maximum number of units of blood to order for some of the commoner surgical procedures. The use of a Type and Screen procedure is recommended for those operations where blood is regularly ordered but rarely used. Operative procedures listed under the Surgical Tables 1 and 2 and the Minor Surgical Procedure Table, Ministry of Health, Singapore, fall into this group.

Malignant histiocytosis--a clinicopathologic study of 5 cases.

The clinico-pathological features of 5 patients with malignant histiocytosis aged 18 years to 73 years seen over a three year period from 1980 to 1983 at the Department of Haematology Singapore General Hospital were studied. Haematological, cytological and histopathological findings of the disease are described. Diagnosis of malignant histiocytosis was established from biopsies of bone marrow, liver, spleen or lymph nodes. Three out of the 5 patients died rapidly after diagnosis despite cytotoxic chemotherapy. One patient was lost to follow up while another is alive surviving so far for 3 months since diagnosis. The differential diagnosis of malignant histiocytosis is also discussed.

A study of the Lewis blood group system in the Singapore population.

The purpose of this retrospective study is to delineate: a) The ethnic group specific distribution patterns of the various Lewis phenotypes in our population in Singapore. b) The occurrence rates of the various anti-Lewis antibodies in our population. The approximate frequencies of the Lewis A-B-, Lewis A-B+ and Lewis A + B- phenotypes in the blood-donor population were estimated to be about 10%, 48% and 42% respectively. It was evident that frequency of the Lewis A-B- phenotype was highest among the Malays, being almost 3 times more frequent than it was among the Chinese (P less than 0.01). The anti-Lewis antibodies were noted to be the commonest irregular antibodies seen in our blood donor population, with an occurrence rate of about 127 per 100,000. Likewise, from 1982 to 1987, the anti-Lewis antibodies were also noted to be the most frequently encountered antibodies in our patient population, accounting for nearly 60% of all cases. Although the Malays comprised only about 15% of the Singaporean population, they accounted for as much as 42.9% of all patients with anti-Lewis antibodies. Similarly, out of all 76 blood donors in 1987 with anti-Lewis antibodies, 50% were found to be Malays although they comprised only 14.28% of the donor population. It was also interesting to note that a sizeable proportion of all patients with anti-Lewis antibodies were pregnant women with or without obstetric complications.

Graft-versus-host disease following sibling allogeneic bone marrow transplantation--the Singapore experience.

Fourteen patients with haematological malignancies received allogeneic bone marrow transplantation from Major Histocompatility Complex compatible siblings. Five (35.7%) patients developed mild and 4 (28.6%) severe graft-versus-host disease (GVHD). There were correlations between the age of recipient (p less than 0.05), the degree of haematological support (p less than 0.1) and GVHD. The effects of the Mixed Lymphocyte Culture reactivity, donor/recipient sex match, cyclosporin A levels and the use of Total Parenteral Nutrition were not apparent. Two patients had relapses of their initial diseases. One of them did not develop any GVHD and the other only mild GVHD post bone marrow transplantation.