Quasispin glass in a geometrically frustrated magnet.

The spin glass state in the spinel ZnCr(2(1-x))Ga(2x)O(4) is studied with magnetization and specific heat for x < 0.05. The freezing temperature is independent of disorder, despite a two-level-like density of states that varies linearly with x. This relationship implies the energy scale for freezing is independent of disorder, in contrast to mean field theories of spin glass. We suggest that the degrees of freedom are shielded spin vacancies, quasispins, which interact via an emergent long-range force mediated by the frustrated spin background.

A Canadian economic analysis of U.S. Oncology Adjuvant Trial 9735.

OBJECTIVES: Recent results of the U.S. Oncology Adjuvant Trial 9735 demonstrated significant disease-free survival and overall survival benefits for docetaxel and cyclophosphamide (tc) compared with doxorubicin and cyclophosphamide (ac) in the adjuvant treatment of operable invasive breast cancer. Based on clinical data from the 9735 study, we evaluated the lifetime cost-effectiveness of tc compared with ac from the perspective of the Canadian publicly funded health care system. METHODS: A Markov model was developed to estimate the incremental cost per quality-adjusted life-year gained and per life-year gained. Monthly survival and risk of disease recurrence up to 7 years were obtained directly from the overall survival and disease-free survival curves in the 9735 study; life-years beyond 7 years were estimated using the average life expectancy of age-matched women in the general Canadian population. Canadian-specific resource utilization and unit costs (in 2008 Canadian dollars) were applied to estimate costs for chemotherapy administration, chemotherapy-related toxicities, recurrence, and adverse events. Health-utility scores and decrements used in the calculation of quality-adjusted life-years were derived from the literature. RESULTS: The lifetime cost per quality-adjusted life-year gained was $8,251 for tc compared with ac, and the cost per life-year gained was $6,842. The results were robust across a range of sensitivity analyses. CONCLUSIONS: Cost-effectiveness, combined with efficacy and an acceptable safety profile, support the adoption of tc as an alternative to ac in Canadian clinical practice for the adjuvant treatment of operable early breast cancer.

Maternal plasma and amniotic fluid angiogenic factors and their receptors in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome.

OBJECTIVE: Angiogenic factors play a role in human placentation and may be aberrant in severe twin-to-twin transfusion syndrome (TTTS). The aim of this study was to investigate the maternal plasma and amniotic fluid angiogenic factor and receptor concentrations in twin pregnancies complicated by TTTS and to evaluate the effects of fetoscopic laser ablation. METHODS: A prospective cohort of monochorionic (MC) twins complicated by severe TTTS (n = 23) was studied between October 2006 and December 2007. A cohort of uncomplicated dichorionic (DC) (n = 12) and MC (n = 7) pregnancies were studied for comparison. Circulating angiogenic factors and their receptors were measured in the maternal plasma and the recipient twin's amniotic fluid by enzyme-linked immunosorbent assay and/or FAST Quant human angiogenesis array. RESULTS: Plasma vascular endothelial growth factor (VEGF)-C concentrations were significantly lower in TTTS than in uncomplicated twin pregnancies (P < 0.0001). In contrast, plasma angiopoietin (Ang)-2 levels and the ratio of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) to placental growth factor (PlGF) levels were significantly increased in TTTS (P < 0.01). Plasma VEGF-D was significantly increased in advanced stage TTTS (Stage III/IV cohort; P < 0.01). This was independent of fetal size, amniotic fluid volumes or the number of apparent placental arteriovenous anastomoses. In TTTS pregnancies, amniotic fluid VEGF-C, VEGF-A, Ang-1 and the sVEGFR-1/PlGF ratio were increased compared to paired maternal plasma concentrations (P < 0.0001) while amniotic fluid concentrations of PlGF, Ang-2 and soluble tyrosine kinase with immunoglobulin-like/epidermal growth factor-like domains 2 (sTie-2) were significantly lower than plasma concentrations (P < 0.0001). No significant association between maternal plasma and amniotic fluid concentrations of angiogenic factors was noted. Plasma PlGF was transiently decreased after fetoscopic laser ablation, returning to baseline by 1 week (P = 0.0314). Fetoscopic laser ablation also affected plasma sVEGFR-1/PlGF ratio with a transient increase after therapy, followed by a significant reduction to below basal concentrations by 1 week (P = 0.0102). Only VEGF-D was significantly different (+8.3%; P = 0.0155) in amniotic fluid immediately after the completion of fetoscopic laser ablation. CONCLUSION: Maternal angiogenic activity is decreased in severe TTTS, with an increased sVEGFR-1/PlGF ratio and concentrations of Ang-2 and VEGF-D in the maternal plasma compared to uncomplicated MC twin pregnancies. Maternal circulating PlGF concentrations decrease and the sVEGFR-1/PlGF ratio increases transiently in response to fetoscopic laser ablation, but in general the angiogenic factor and receptor concentrations studied are altered little by this therapy.

Iron supplement in pregnancy and development of gestational diabetes--a randomised placebo-controlled trial.

OBJECTIVE: To test the hypothesis that iron supplement from early pregnancy would increase the risk of gestational diabetes mellitus (GDM). DESIGN: Randomised placebo-controlled trial. SETTING: A university teaching hospital in Hong Kong. POPULATION: One thousand one hundred sixty-four women with singleton pregnancy at less than 16 weeks of gestation with haemoglobin (Hb) level between 8 and 14 g/dl and no pre-existing diabetes or haemoglobinopathies. METHODS: Women were randomly allocated to receive 60 mg of iron supplement daily (n= 565) or placebo (n= 599). Oral glucose tolerance tests (OGTTs) were performed at 28 and 36 weeks. Women were followed up until delivery. OUTCOME MEASURES: The primary outcome was development of GDM at 28 weeks. The secondary outcomes were 2-hour post-OGTT glucose levels, development of GDM at 36 weeks and delivery and infant outcomes. RESULTS: There was no significant difference in the incidence of GDM in the iron supplement and placebo groups at 28 weeks (OR: 1.04, 95% confidence interval [CI]: 0.7-1.53 at 90% power) or 36 weeks. Maternal Hb and ferritin levels were higher in the iron supplement group at delivery (P < 0.001 and P= 0.003, respectively). Elective caesarean section rate was lower in the iron supplement group (OR: 0.58, 95% CI: 0.37-0.89). Infant birthweight was heavier (P= 0.001), and there were fewer small-for-gestational-age babies in the iron supplement group (OR: 0.46, 95% CI: 0.24-0.85). CONCLUSION: Iron supplement from early pregnancy does not increase the risk of GDM. It may have benefits in terms of pregnancy outcomes.

Maternal serum markers of placental damage in uncomplicated dichorionic and monochorionic pregnancies in comparison with monochorionic pregnancies complicated by severe twin-to-twin transfusion syndrome and the response to fetoscopic laser ablation.

OBJECTIVE: Twin-to-twin transfusion syndrome (TTTS) is a morbid perinatal condition associated with abnormal placentation and is treated by fetoscopic laser ablation (FLA). We assessed basal maternal serum alphafetoprotein (MSAFP) and free beta-human chorionic gonadotrophin (f-betaHCG) in uncomplicated dichorionic (DC) and monochorionic (MC) twin pregnancies and a cohort of MC twin pregnancies complicated by severe TTTS. Changes in MSAFP and f-betaHCG post-FLA were measured as markers of placental coagulation. STUDY DESIGN: In a prospective case-cohort study, MC twins complicated by TTTS (n=23) were studied. A cohort of uncomplicated DC (n=12) and MC (n=6) twin pregnancies, which were appropriately grown for gestation with normal liquor volumes were also studied. Using solid phase, two site fluoroimmunometric assays, both MSAFP and f-betaHCG from uncomplicated and complicated cohorts were measured. Samples were taken, prior to FLA then at intervals after the procedures (6h, 24h and 1 week). RESULTS: The median multiples of median (MoM) were not significantly different in uncomplicated DC twin pregnancies for MSAFP 1.85 (95% CI 1.62-2.34) or fbetaHCG 1.66 (95% CI 1.21-2.04) compared to uncomplicated MC twin pregnancies (MSAFP 1.40 (95% CI 1.16-2.58) and fbetaHCG 1.70 (95% CI 0.32-3.35)). However, the median MSAFP MoM in MC twin pregnancies complicated by severe TTTS was increased (MSAFP 3.10 (95% CI 2.67-4.43); p<0.05) with a more significant increase being noted in median fbetaHCG (MoM 5.75 (95% CI 5.22-9.12); p<0.0001) compared to uncomplicated twin pregnancies. Post-FLA, the median MSAFP increased significantly at 6h by 445% (636.65 U/ml (95% CI 616-1216.9 U/ml)) and remained elevated at 1 week (553.4 U/ml (95% CI 203.7-3020.8 U/ml; p=0.001)). No significant difference in median fbetaHCG was noted post-FLA (p=0.36). This rise in MSAFP appears unrelated to the number of placental anastomoses coagulated or the total energy used. Also, in the small cohort in which amniodrainage alone was performed no rise in MSAFP was noted. CONCLUSIONS: MSAFP and fbetaHCG are increased in TTTS indicating an association with abnormal placentation. Post-FLA, a significant rise in MSAFP was noted for up to a week post-coagulation. This was not noted after amniodrainage.

Conservative management of placenta praevia with accreta.

It has been advocated that placenta accreta/percreta should be managed conservatively to avoid massive pelvic bleeding and preserve fertility. Diagnosis of this condition with high-resolution imaging investigations performed during the antenatal period facilitates discussion of management plans with other clinical disciplines (eg interventional radiologists), the patient, and her family. Three cases of placenta praevia with accreta are presented. The three cases were managed by leaving the placenta in-utero after caesarean section, using uterine arterial embolisation to control postpartum haemorrhage only when needed. In all these cases, we succeeded in conserving the uterus without major complications. With improved imaging techniques, accurate antenatal diagnosis of placenta praevia with accreta is now possible. This new approach to conservative management can be considered in order to not only conserve the uterus but also to avoid uncontrolled pelvic haemorrhaging.

Application of transcervical hysterofetoscopy and cord blood collection at first trimester termination of pregnancy for fetal abnormalities.

OBJECTIVE: To examine the applicability of hysterofetoscopy and cord blood collection at first trimester termination of pregnancy for fetal abnormalities. METHODS: From 2004 to 2007, transcervical hysterofetoscopy was performed in seven patients at the same operation setting of surgical termination of pregnancy. The findings were compared with prenatal diagnosis. Feasibility of cord blood collection was also examined. RESULTS: Out of these seven patients, six of them had prenatal ultrasound diagnosis of cystic hygroma. All of them had chromosomal abnormalities. Subcutaneous oedema was confirmed by hysterofetoscopy with good view. Another pregnancy was complicated by homozygous alpha thalassaemia and the diagnosis was confirmed by electrophoresis of fetal haemoglobin collected from umbilical cord vessel. Cord blood collection was also attempted in two other patients yielding fetal blood with minimal maternal contamination. CONCLUSION: Transcervical hysterofetoscopy is a feasible tool in confirming external fetal structural abnormalities before surgical termination of pregnancy. It can be performed under either general anaesthesia or conscious sedation. Umbilical cord blood collection can facilitate confirmation of genetic diseases. It may also allow the potential of isolating fetal mesenchymal stem cell in first trimester.

Comparison of nuchal and detailed morphology ultrasound examinations in early pregnancy for fetal structural abnormality screening: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of a nuchal scan at 10 to 14 + 6 weeks and a detailed morphology scan at 12 to 14 + 6 weeks in screening for fetal structural abnormalities. METHODS: From March 2001 to November 2004, 8811 pregnant women were randomized into either the control group (10 to 14 + 6-week nuchal scan followed by routine 16-23-week scan) or the study group (10 to 14 + 6-week nuchal scan and 12 to 14 + 6-week detailed scan followed by routine 16-23-week scan). RESULTS: We analyzed 7642 cases of singleton pregnancies with viable fetuses at first-trimester ultrasound examination and with known pregnancy outcome. In the control group, the detection rate of structural abnormalities in the first trimester was 32.8% (21/64; 95% CI, 21.6-45.7%) and the overall detection rate was 64.1% (41/64; 95% CI, 51.1-75.7%). In the study group, the detection rate in the first trimester was 47.6% (30/63; 95% CI, 34.9-60.6) and the overall detection rate was 66.7% (42/63; 95% CI, 53.7-78.0%). The overall detection rate in the control group did not differ significantly from that in the study group (P > 0.05). CONCLUSIONS: When the nuchal scan is offered, a basic anatomical survey can be done in conjunction with nuchal translucency thickness measurement. A detailed ultrasound examination at this early gestational age may not be superior to the nuchal scan in screening for fetal abnormalities in the low-risk population. Though a wide range of abnormalities can be detected at 10 to 14 + 6 weeks, the routine 16-23-week scan cannot be abandoned.

BRE is an antiapoptotic protein in vivo and overexpressed in human hepatocellular carcinoma.

BRE binds to the cytoplasmic domains of tumor necrosis factor receptor-1 and Fas, and in cell lines can attenuate death receptor-initiated apoptosis by inhibiting t-BID-induced activation of the mitochondrial apoptotic pathway. Overexpression of BRE by transfection can also attenuate intrinsic apoptosis and promote growth of the transfected Lewis lung carcinoma line in mice. There is, however, a complete lack of in vivo data about the protein. Here, we report that by using our BRE-specific monoclonal antibody on the immunohistochemistry of 123 specimens of human hepatocellular carcinoma (HCC), significant differences in BRE expression levels between the paired tumoral and non-tumoral regions (P<2.2e-16) were found. Marked overexpression of BRE was detected in majority of the tumors, whereas most non-tumoral regions expressed the same low level of the protein as in normal livers. To investigate whether BRE overexpression could promote cell survival in vivo, liver-specific transgenic BRE mice were generated and found to be significantly resistant to Fas-mediated lethal hepatic apoptosis. The transgenic model also revealed post-transcriptional regulation of Bre level in the liver, which was not observed in HCC and non-HCC cell lines. Indeed, all cell lines analysed express high levels of BRE. In conclusion, BRE is antiapoptotic in vivo, and may promote tumorigenesis when overexpressed.

IVIG for the treatment of toxic epidermal necrolysis.

Intravenous immunoglobulin (IVIG) has been proposed as a treatment for toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS). A number of retrospective and prospective studies have been conducted, with varying levels of evidence for the efficacy of IVIG. Recent publications provide opposing conclusions. A multi-center, comparative, long-term analysis needs to be conducted to determine the role of IVIG in the management of patients with SJS/TEN.

Continued reduction in the incidence of birth trauma and birth asphyxia related to instrumental deliveries after the study period: was this the Hawthorne effect?

BACKGROUND: The incidence of birth trauma and birth asphyxia related to instrumental deliveries in our obstetric unit was high (2.8%) in 1998-1999. A study was performed in 2000 to identify the risk factors. Unexpectedly, the incidence (0.6%) was reduced significantly during the study period. We attributed this phenomenon to the famous Hawthorne effect (tendency to improve performance because of awareness of being studied). OBJECTIVES: The objectives were to study whether there is a continued reduction in the incidence of birth trauma and birth asphyxia related to instrumental deliveries in the post-study period (2001-2003) and to investigate the presence of underlying confounding factors apart from the Hawthorne effect. METHOD: To compare the hospital obstetric statistics among the pre-study period (1998-1999), the study period (2000) and the post-study period (2001-2003), in particular the incidence of birth trauma and birth asphyxia related to instrumental deliveries, the instrumental delivery rate, the overall Caesarean section rate, the Caesarean section rate for no progress of labour, the incidence of failed instrumental delivery, the incidence of attempted instrumental delivery in the operating theatre, and incidence of direct second-stage Caesarean sections. RESULTS: The incidence of birth trauma and birth asphyxia related to instrumental deliveries (0.6%) during the study period (2000) was significantly lower than that (2.8%) during the pre-study period (1998-1999; RR 0.27, 95% CI 0.11-0.70). This phenomenon continued into the post-study period (2001-2003) when the incidence of 1.0% was similarly lower than that in the pre-study period (RR 0.35, 95% CI 0.20-0.64). The instrumental delivery rate decreased further in the post-study period (13.5%) compared with those in the study (16.6%) and pre-study (19.5%) periods (RR 0.81, 95% CI 0.75-0.89 and RR 0.69, 95% CI 0.65-0.74, respectively). There was a marked increase in the direct second-stage Caesarean section rate in the post-study period (7.1%) compared to those in the study (0.4%) and pre-study (0.7%) periods (RR 15.9, 95% CI 5.05-49.73 and RR 9.77, 95% CI 5.28-18.08, respectively). CONCLUSION: A change in obstetric practice was identified that may explain the continued reduction in the incidence of birth trauma and birth asphyxia related to instrumental deliveries in the post-study period.

Three-dimensional extended imaging: a new display modality for three-dimensional ultrasound examination.

OBJECTIVE: To describe Three-Dimensional eXtended Imaging (3DXI) as a new display modality for three-dimensional (3D) ultrasound examination of the fetus. METHODS: The spine, palate, heart and brain were evaluated using 3D ultrasound examination at a mean gestational age of 22 weeks in 35, 31, 32 and 31 fetuses, respectively. The volume data captured were analyzed using the conventional orthogonal display mode (ODM), as well as the 3DXI, which includes the Multi-Slice View (MSV) mode and the Oblique View (OBV) mode. The MSV mode allows simultaneous display of multiple sequential parallel planes while the OBV mode allows examination of a non-standard straight or curved plane. RESULTS: The MSV mode allowed a simultaneous display of multiple sequential parallel planes of the fetal structures, but we found some uncertainty if an isolated image in one of the multi-slice images represented the exact level of a fetal structure. The MSV mode was advantageous in one of the six cases of facial cleft by allowing the simultaneous display of bilateral clefts that were located in two different axial planes. The multi-slice images were helpful in making the diagnosis in one case of holoprosencephaly. The OBV mode allowed examination of the coronal plane across the curvature of the spine, and the 'in-plane' view of the interventricular septum in a non-gated study. CONCLUSION: The 3DXI can display the volume data in a different manner from that which usually results from the use of more conventional ODM, and provide additional information over conventional two-dimensional sonography.

Primary B-cell lymphoma and lymphoma-like lesions of the uterine cervix.

We present three patients with atypical lymphoid cells on cervical smear screening, with diffuse large-cell B-cell lymphoma diagnosed by morphology on cervical biopsy. One patient with extensive pelvic disease was treated with chemotherapy and radiotherapy and remained in remission 8 years later. Two patients with presumed stage 1E lesions showed spontaneous regression on repeat cervical biopsy, despite light chain restriction and clonal immunoglobulin gene rearrangement. They are without recurrent malignancy 1 and 5 years after their initial diagnosis. The presence of malignant looking lymphoid cells on cervical smear should be investigated by repeated colposcopic biopsies. The reason for the highly skewed atypical B-cell lymphoproliferation in lymphoma-like lesions of the cervix is unknown. With early stage, nonbulky cervical lymphoma in an otherwise healthy patient, a cone biopsy is advised. A number of these lesions may regress even when clonal populations are detected.

Expression of human BRE in multiple isoforms.

BRE, a putative stress-modulating gene, found able to down-regulate TNF-alpha-induced NF-kappaB activation upon overexpression, is now shown in human cells expressed as multiple mRNA isoforms. A total of six isoforms are produced by alternative splicing predominantly at either end of the gene. Predicted from the cDNA sequences of these isoforms, three of them (alpha(a), alpha(b), and alpha(c)) code for BRE of different C-terminus, and the other three (beta(a), beta(b), and beta(c)) may possibly be the nonfunctional counterparts. All human cells examined coexpress all the predominant splice variants, albeit at different ratios. Comparing with normal cells, immortalized human cell lines uniformly express higher levels of BRE. Interestingly, peripheral blood monocytes responded to LPS by down-regulating the expression of all the BRE isoforms, which was however less obvious in the cell line counterpart, THP-1. Isoform alpha(a), which codes for the canonical BRE with a C-terminal peroxisomal targeting sequence, is the most abundant transcript. We propose that the function of BRE and its isoforms is to regulate peroxisomal activities.

Influence of parity on the obstetric performance of mothers aged 40 years and above.

We reviewed the delivery records of 205 mothers aged 40 years and above who delivered from 1st January 1994 to 31st December 1996 to examine the influence of parity on their obstetric performance. There were 51 (24.9%) primiparous mothers. The incidences of antenatal complications (antepartum haemorrhage, hypertensive disorder, glucose intolerance, prematurity), labour performance (type of labour, mode of delivery) and neonatal outcome (birth weight, Apgar scores, neonatal intensive care unit admission, perinatal mortality) were compared between the 51 (24.9%) primiparous and the 154 (75.1%) multiparous mothers. Higher incidences of antepartum haemorrhage (17.6 versus 5.8%, P = 0.0188), hypertensive disorder (17.6 versus 5.2%, P = 0.015), labour induction (33.3 versus 14.3%, P = 0.004) and Caesarean section delivery (58.8 versus 20.8%, P < 0.0001) were found among the primiparous mothers than the multiparous group. Neonatal outcome, however, was similar in both groups. We conclude that the primiparous mothers aged 40 years and above had more complicated antenatal and labour courses than multiparous mothers. On the other hand, the neonatal outcomes of two groups were comparable.

Wavelet analysis of embolic heart sound detected by precordial Doppler ultrasound during continuous venous air embolism in dogs.

UNLABELLED: The spectrum of the embolic heart sounds (EHS) detected by precordial Doppler ultrasound has been previously characterized, but only on small volumes of venous air embolism (VAE). We sought to determine whether real-time wavelet analysis is useful in analyzing the signals of EHS and whether the embolic power of the EHS for larger volumes of air is proportionate to the volume of VAE that has been reported for small volumes of VAE. A series of small air boli (0.01, 0.02, 0.05, 0.07, 0.1, 0.15, 0.2, 0.3, 0.4, and 0.8 mL), followed by continuous infusion of larger volumes of air (0.8, 1.6, 2.4, 4.8, and 9.6 mL), was injected into the external jugular vein through a central catheter in seven pentobarbital-anesthetized dogs. We measured the spectrum of the Doppler heart sound (DHS) in a real-time manner by using wavelet analysis at different scales. Wavelet analysis at scale = 1 yielded satisfactory results in distinguishing abnormal EHS from normal DHS with high sensitivity (100%) and good positive predictive value (100%) compared with the conventional method, which requires an anesthesiologist to listen to the audio DHS signals in a real-time manner. There was a linear relationship (y = 1.08x + 7.89, r = 0.75, P < 0.001) between the cumulative embolic power of the EHS and the air volume introduced in the form of either bolus or continuous infusion. The 95% confidence intervals for slope and intercept were 0.89-1.27 and 7.65-8.13, respectively. Our results suggest that wavelet analysis is effective as a real-time monitor and that it is possible to distinguish larger volumes of air emboli based on previous injections of small volumes of air. IMPLICATIONS: The real-time wavelet analysis of the heart sound detected by precordial Doppler ultrasound may be useful in estimating larger volumes of air emboli based on previous injections of small volumes of air in anesthetized dogs.

Fast detection of venous air embolism in Doppler heart sound using the wavelet transform.

The introduction of air bubbles into the systemic circulation can result in significant morbidity. Real-time monitoring of continuous heart sound in patients detected by precordial Doppler ultrasound is, thus, vital for early detection of venous air embolism (VAE) during surgery. In this study, the multiscale feature of wavelet transforms (WT's) is exploited to examine the embolic Doppler heart sound (DHS) during intravenous air injections in dogs. As both humans and dogs share similar physiological conditions, our methods and results for dogs are expected to be applicable to humans. The WT of DHS at scale 2j (j = 1, 2) selectively magnified the power of embolic, but not the normal, heart sound. Statistically, the enhanced embolic power was found to be sensitive (P < 0.01 at 0.01 ml of injected air) and correlated significantly (P < 0.0005, r = 0.83) with the volume of injected air from 0.01 to 0.10 ml. A fast detection algorithm of O(N) complexity with unit complexity constant for VAE was developed (processing speed = 8 ms per heartbeat), which confirmed the feasibility of real-time processing for both humans and dogs.