Diffusion tensor imaging of anisotropic inhomogeneous turbulent flow.

Inhomogeneous anisotropic turbulent flow is difficult to measure, and yet it commonly occurs in nature and in many engineering applications. This work aims to introduce a technique based on magnetic resonance imaging which can spatially map the degree of turbulence as well as the degree of anisotropy. Our interpretation relies on the eddy diffusion model of turbulence, and combines this with the technique of diffusion tensor imaging. The result is an eddy diffusion tensor, which is represented by a symmetric three-by-three matrix. This tensor contains a wealth of information about the magnitude and directions of the turbulent fluctuations; however, the correlation time must be considered before interpreting this information. In the constricted pipe flow used in this study, the turbulence is greatest in magnitude in the space surrounding the core of the turbulent jet, and the turbulence is highly anisotropic.

Time-resolved nanosecond optical pyrometry of the vapor to plasma transitions in exploding bridgewires.

Electrically exploded wires find uses throughout high-energy physics. For example, they are commonly used as high-temperature sources, X-ray generators, and in precision timing detonators. However, the detailed and complete physics that occurs is complex and still poorly understood. A full mechanistic description of these complex phenomena is beyond the scope of a single paper. Instead, we focus on the formation of metal vapor and its transition to plasma. This single transition is commonly assumed to comprise "bridge-burst". We use a suite of diagnostics including a novel, fiber-based, high-speed, optical pyrometer to better characterize this transition. The primary finding from this project is that peak light output from an exploding wire does not temporally match the peak temperature. Additionally, it is found that peak light does not align with peak bridge-burst voltage and that the peak temperature is not voltage-dependent. These findings are non-intuitive and will allow for the correction of false assumptions previously made about this topic.

Association between maternal psychological adversity and lung function in South African infants: A birth cohort study.

OBJECTIVE: The association of perinatal psychological adversity (ie, stressors and distress) with infant lung function (ILF) and development is not well studied in Africa and elsewhere. We determined the association between maternal perinatal psychological adversity and ILF in African infants. DESIGN: Prospective longitudinal follow up of the Drakenstein Child Health Study birth cohort. PARTICIPANTS: Seven hundred and sixty-two infants aged 6 to 10 weeks and 485 infants who had data for both maternal perinatal psychological adversity and ILF (measured at 6 to 10 weeks and 12 months). METHODS: The main analyses were based on cross-sectional measures of ILF at each assessment (6 to 10 weeks or 12 months), using generalized linear models, and then on the panel-data of both longitudinal ILF assessments, using generalised estimating equations, that allowed specification of the within-group correlation structure. RESULTS: Prenatal intimate partner violence (IPV) exposure was associated with reduced respiratory resistance at 6 to 10 weeks (beta coefficient [ß] = -.131, P = .023); postnatal IPV with reduced ratio of time to peak tidal expiratory flow over total expiratory time (tPTEF /tE ) at 12 months (ß = -.206, P = .016); and prenatal depression with lower respiratory rate at 6 to 10 weeks (ß = -.044, P = .032) and at 12 months (ß = -.053, P = .021). Longitudinal analysis found an association of prenatal IPV with reduced tPTEF /tE (ß = -.052, P < .0001); postnatal IPV with decreased functional residual capacity (FRC; ß = -.086, P < .0001); prenatal posttraumatic stress disorder with increased FRC (ß = .017, P < .0001); prenatal depression with increased FRC (ß = .026, P < .0001) and postnatal depression with increased FRC (ß = .021, P < .0001). CONCLUSION: Screening for psychological adversity and understanding the mechanisms involved may help identify children at risk of altered lung development and inform approaches to treatment.

Impact of HIV and antiretroviral drug exposure on lung growth and function over 2 years in an African Birth Cohort.

OBJECTIVE: To assess the impact of HIV and antiretroviral exposure without infection on lung growth and function over the first 2 years of life. DESIGN: Prospective observational study of an African birth cohort, Drakenstein Child Health Study. METHOD: Infants enrolled antenatally had lung function measured at 6 weeks, 1 and 2 years. HIV-infected women received antiretroviral therapy (ART) as per local guidelines. The association between HIV and antiretroviral exposure with lung function was assessed using mixed effects modelling. RESULTS: Of 1143 infants born, two HIV-infected infants were excluded from analysis; 909 (80%) infants had lung function collected at 6 weeks [190 (21%) were HIV-exposed uninfected (HEU)]; 782 (69%) at 1 year and 741 (65%) at 2 years. At 6 weeks HEU infants had larger tidal volume compared with HIV-unexposed infants (1.13 ml, confidence interval: 0.02-2.23, P = 0.045). High maternal viral load was associated with a 17% lower expiratory flow over 2 years (0.17, confidence interval 0.00-0.34, P = 0.046). First-line ART initiated during pregnancy was associated with lower infant tidal volume at 6 weeks compared with those who initiated ART before pregnancy (-2.7 ml, -5.31 to -0.10, P = 0.042), and low maternal CD4 cell counts associated with lower infant tidal over 2 years (-11.1 ml, -18.58-3.58, P = 0.004). CONCLUSION: HIV exposure is associated with altered lung function in early life, with a vulnerable HEU subgroup based on maternal disease severity, immunological compromise and ART exposure. These data highlight the importance of ongoing surveillance of respiratory health in HEU children.

Determining velocity of detonation using high-resolution time domain reflectometry.

Two methods are presented to make measurements of the length of a coaxial cable with submillimeter and submicrosecond accuracy. If the cable is destroyed by the passage of a strong shock, for instance, from the detonation of an explosive, a measure of the phase velocity of the detonation (VOD) can be obtained with high accuracy (≈0.25%). The first method introduces a series of short Gaussian electrical pulses (<300 ps) into the cable that reflect off the cable end and are compared to the time of the original outgoing pulse by using a fast digitizer (100 gigasamples per second). By curve fitting a Gaussian form to the outgoing and reflected pulses, a measurement of the cable length can be made with subsample accuracy. So, as long as the pulses do not overlap, a large number may be present in the cable at any time allowing pulse repetition rates of 40-135 MHz depending on the cable length. Averaging allows accurate VOD measurements to be made that are comparable with the best traditional techniques. The second method replaces the pulser with a wide-spectrum (0.1-10 GHz) amplified random noise source. A similar setup and digitizer are used before autocorrelating short (80-160 ns) subsamples of the total waveform to measure the reflected delay time. That is, a smaller amplitude version of the original waveform appears time shifted by twice the transit time in the cable and this time is estimated via autocorrelation. The advantage of this method is that a new subsample needs only to be selected from a time increment in which new spectral information is present for a new measure of the length to be made. In this manner, many more length estimates can be averaged to establish the VOD than with the Gaussian approach. A detailed description of the implementation of both methods is presented together with an example of the type of data collected and limitations found.

A review of the mechanism by which exploding bridge-wire detonators function.

An introduction to exploding bridge-wire (EBW) detonators is given followed by an extensive critical review of open source literature pertaining to these devices. The aim is to better establish the mechanism of operation. Some authors state that the key mechanism is shock-to-detonation while others maintain it is more thermal in nature, or a complex combination of both. In addition to EBW detonators, arc detonators and direct optical initiation detonators are also reviewed, and it is demonstrated that in this manner the usually coupled effects from both shock and deflagration can be somewhat decoupled. As a result, it is hypothesized that the mechanism of operation in all three detonators is in fact the same: the formation of a hot plasma with a power of ≈1 MW and emission in the ultraviolet drives a thermal explosion process.

Associations between maternal mental health and early child wheezing in a South African birth cohort.

BACKGROUND: Wheezing in early childhood is common and has been identified in high-income countries (HIC) as associated with maternal antenatal or postnatal psychosocial risk factors. However, the association between maternal mental health and childhood wheezing has not been well studied in low and middle-income countries (LMIC), such as South Africa. METHODS: A total of 1137 pregnant women over 18 year old, between 20 and 28 weeks' gestation, and attending either of two catchment area clinics were enrolled in a South African parent study, the Drakenstein Child Health Study (DCHS). Psychosocial risk factors including maternal depression, psychological distress, early adversity, and intimate partner violence (IPV), were measured antenatally and postnatally by validated questionnaires. Two outcomes were evaluated: Presence of wheeze (at least one episode of child wheeze during the first 2 years of life); and recurrent wheeze (two or more episodes of wheezing in a 12-month period). Logistic regression was used to investigate the association between antenatal or postnatal psychosocial risk factors and child wheeze, adjusting for clinical and socio-demographic covariates. RESULTS: Postnatal psychological distress and IPV were associated with both presence of wheeze (adjusted OR = 2.09, 95%CI: 1.16-3.77 and 1.63, 95%CI: 1.13-2.34, respectively), and recurrent child wheeze (adjusted OR = 2.26, 95%CI: 1.06-4.81 and 2.20, 95%CI: 1.35-3.61, respectively). CONCLUSION: Maternal postnatal psychological distress and IPV were associated with wheezing in early childhood. Thus, screening and treatment programs to address maternal psychosocial risk factors may be potential strategies to reduce the burden of childhood wheeze in LMICs.

Looks can be deceiving: A case of placental mesenchymal dysplasia with concomitant cytomegalovirus infection / Philippine Journal of Obstetrics and Gynecology

Pregnancy with placental mesenchymal dysplasia (PMD), with concomitant cytomegalovirus (CMV) infection, and with coexistent normal viable fetus is very rare. An 18 year old, Gravida 2 Para 0 (0-0-1-0), was referred to our institution at 24 weeks age of gestation, with impression of molar pregnancy with a live twin fetus. Subsequent ultrasound revealed placentomegaly with placental features similar to hydatidiform mole. Her pregnancy was complicated with intrauterine growth restriction (IUGR) and oligohydramnios. TORCH panel at 25 weeks age of gestation revealed positive for CMV IgG. She had normal serum ?-HCG, with elevated maternal serum alpha feto protein (msAFP). A caesarean section was done at 37 weeks age of gestation for placenta previa marginalis in haemorrhage. She delivered a live baby girl, APGAR score of 9,9, maturity testing of 37 weeks, small for gestational age. The baby was also positive for CMV IgG. Gross examination of the placenta revealed tortuous vessels and multiple cystic spaces. Histopatho-logically, there were hydropic stem villi with no trophoblastic proliferation. Immunohistochemically, placental mesenchymal dysplasia was confirmed.

Long-term clinical response to cardiac resynchronisation therapy under a multidisciplinary model.

BACKGROUND: Cardiac resynchronisation therapy (CRT) is established in the management of cardiac failure in patients with systolic dysfunction. Clinical response to CRT is not uniform, and response has been difficult to predict. AIM: Patient management within a high volume, multidisciplinary service focused on optimal delivery of CRT would improve response rates. METHODS: Four hundred and thirty-five consecutive patients who underwent CRT under a multidisciplinary heart failure service were enrolled prospectively over a 5-year period. Medically optimised, symptomatic patients with an ejection fraction (EF) <35%, widened QRS or abnormal dyssynchrony index were included. Left ventricular lead position was targeted anatomically to the segment of latest mechanical activation, and electrically to a site with maximal intrinsic intracardiac electrogram separation. Routine device and clinical follow up, as well as CRT optimisations, were performed at baseline and at 3-monthly intervals. Responders were defined as having an absolute reduction in left ventricular end-diastolic diameter >10% and an improvement in EF >5%. RESULTS: With a mean follow up of 53 ± 11 months, response rate to CRT was 81%. Mean EF improved from 26 ± 10% to 37 ± 11%, and mean left ventricular end-diastolic diameter reduced from 68.6 ± 9.2 mm to 57.8 ± 9.3 mm. Predictors of response were sinus rhythm, high dyssynchrony index and intrinsic electrical dyssynchrony >80 ms. Successful LV lead implantation at initial procedure was achieved in 99.1%, and at latest follow up 94.6% of initial LV leads were still active. CONCLUSION: CRT undertaken with a unit focus on optimal LV lead positioning and device optimisation, along with a multidisciplinary follow-up model, results in an excellent response rate to CRT.

Kaposi's sarcoma-associated herpesvirus inhibits expression and function of endothelial cell major histocompatibility complex class II via suppressor of cytokine signaling 3.

Endothelial cells (EC) can present antigen to either CD8(+) T lymphocytes through constitutively expressed major histocompatibility complex class I (MHC-I) or CD4(+) T lymphocytes through gamma interferon (IFN-γ)-induced MHC-II. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), an EC neoplasm characterized by dysregulated angiogenesis and a substantial inflammatory infiltrate. KSHV is understood to have evolved strategies to inhibit MHC-I expression on EC and MHC-II expression on primary effusion lymphoma cells, but its effects on EC MHC-II expression are unknown. Here, we report that the KSHV infection of human primary EC inhibits IFN-γ-induced expression of the MHC-II molecule HLA-DR at the transcriptional level. The effect is functionally significant, since recognition by an HLA-DR-restricted CD4(+) T-cell clone in response to cognate antigen presented by KSHV-infected EC was attenuated. Inhibition of HLA-DR expression was also achieved by exposing EC to supernatant from KSHV-inoculated EC before IFN-γ treatment, revealing a role for soluble mediators. IFN-γ-induced phosphorylation of STAT-1 and transcription of CIITA were suppressed in KSHV-inoculated EC via a mechanism involving SOCS3 (suppressor of cytokine signaling 3). Thus, KSHV infection resulted in transcriptional upregulation of SOCS3, and treatment with RNA interference against SOCS3 relieved virus-induced inhibition of IFN-γ-induced STAT-1 phosphorylation. Since cell surface MHC-II molecules present peptide antigens to CD4(+) T lymphocytes that can function either as direct cytolytic effectors or to initiate and regulate adaptive immune responses, inhibition of this antigen-presenting pathway would provide a survival advantage to the virus.

Kaposi's sarcoma-associated herpesvirus infection of endothelial cells inhibits neutrophil recruitment through an interleukin-6-dependent mechanism: a new paradigm for viral immune evasion.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), an endothelial cell (EC) neoplasm characterized by dysregulated angiogenesis and inflammation. KSHV infection of EC causes production of proinflammatory mediators, regarded as possible initiators of the substantial mononuclear leukocyte recruitment seen in KS. Conversely, KSHV immune evasion strategies exist, such as degradation of EC leukocyte adhesion receptors by viral proteins. Here, we report the effects of KSHV infection of primary EC on recruitment of flowing leukocytes. Infection did not initiate adhesion of any leukocyte subset per se. However, on cytokine-stimulated EC, KSHV specifically inhibited neutrophil, but not PBL or monocyte, transmigration, an observation consistent with the inflammatory cell profile found in KS lesions in vivo. This inhibition could be recapitulated on uninfected EC using supernatant from infected cultures. These supernatants contained elevated levels of human interleukin 6 (hIL-6), and both the KSHV- and the supernatant-induced inhibitions of neutrophil transmigration were abrogated in the presence of a hIL-6 neutralizing antibody. Furthermore, preconditioning of EC with hIL-6 mimicked the effect of KSHV. Using RNA interference (RNAi), we show that upregulation of suppressor of cytokine signaling 3 (SOCS3) was necessary for this effect of hIL-6. These studies reveal a novel paracrine mode of KSHV immune evasion, resulting in reduced recruitment of neutrophils, a cell type whose antiviral and antitumor roles are becoming increasingly appreciated. Moreover, the findings have implications for our understanding of the contribution of hIL-6 to the pathogenesis of other inflammatory disorders and tumors in which this cytokine is abundant.

UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia.

Nilotinib is a novel BCR-ABL inhibitor with significantly improved potency and selectivity over imatinib. In Phase I and Phase II clinical studies of nilotinib in patients with a variety of leukemias, infrequent instances of reversible, benign elevation of bilirubin were observed. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) glucuronidates bilirubin in humans, and a polymorphism in the promoter of the gene that encodes it has been associated with hyperbilirubinemia during treatment with a number of drugs. Pharmacogenetic analysis of that TA-repeat polymorphism found an association between the (TA)7/(TA)7 genotype and risk of hyperbilirubinemia in Phase I patients with imatinib-resistant/intolerant chronic myeloid leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL); this result was replicated in two separate analyses of the chronic phase (CP) and accelerated phase (AP) CML arms of a Phase II study. As nilotinib is not known to be glucuronidated by UGT1A1, the combined impact of inhibition of UGT1A1 activity by nilotinib and genetic polymorphism is the most likely cause of the increased rate of hyperbilirubinemia.

The effect of tibial implant size on post-operative alignment following medial unicompartmental knee replacement.

We have retrospectively reviewed a consecutive series of 71 medial unicompartmental knee replacements in 56 patients performed between 1991 and 1996 by a single surgeon. The aim of this study was to quantify the amount of correction in the tibiofemoral angle, which is achievable with each thickness of polyethylene tibial insert. Our results have shown that the amount of correction which can be expected with an 8 mm, 10 mm, 12 mm and 14 mm insert are 5.3 degrees, 4.8 degrees, 6.6 degrees and 9.5 degrees, respectively. These results will act as a useful reference for surgeons who perform this procedure.

Construction of a high-resolution moiré interferometer for investigating microstructural displacement fields in materials.

A high-magnification moiré interferometer has been constructed with a spatial resolution of the order of 1 microm to measure the local in-plane displacement field associated with a material's microstructure. Laser illumination passes through phase-stepping optics and is delivered to the microscope head by polarization-preserving single-mode optical fibres. The head itself is a compact unit consisting of collimating optics, an objective lens and a charge coupled device (CCD) camera. Thin-phase gratings are cast onto the sample surface with a compliant epoxy resin and coated with ca. 5 nm of gold to enhance the fringe contrast and reduce speckle noise. By switching between the laser illumination and white-light illumination, the underlying microstructure is viewed in exact registration with the measured displacement fields. The application of the instrument is illustrated here by visualization of displacement fields in polymer-bonded explosives (PBXs) during deformation to failure. PBXs are highly filled polymers consisting of up to 95% by weight crystalline explosive bound in a variety of polymeric binders. The mechanical properties of PBXs are highly dependent on the microstructure, and moiré interferometry is an ideal tool for investigating the relationship between the 1-100 microm sized crystals and the displacement fields. Methods such as this are required if computer models of inhomogeneous materials are to be accurately validated.

The occurrence of Trypanosoma evansi in buffaloes in Indonesia, estimated using various diagnostic tests.

The prevalence and incidence of Trypanosoma evansi infections in village buffaloes in Central Java were estimated using parasitological tests, two antigen-detection ELISAs (2G6 Ag-ELISA and Tr7 Ag-ELISA), an antibody-detection ELISA (IgG ELISA) and a card agglutination test (CATT). Of 2387 village buffaloes tested in five districts, 4 % (95 % confidence interval [CI]: 3 %, 5 %) were positive with the microhaematocrit test (MHCT), 58 % (95 % CI: 56 %, 60 %) were positive with the 2G6 Ag-ELISA and 70 % (95 % CI: 68 %, 72 %) were positive with the Tr7 Ag-ELISA. An increasing prevalence with age was found and the proportion of positive buffaloes was highest in the over 84 months-old age-group (68 %) with the 2G6 Ag-ELISA and in the 37-60 months-old age-group (78 %) with the Tr7 Ag-ELISA. Parasitaemic buffaloes were found in more than half of the villages visited. Corrected village-specific prevalence values obtained with the two Ag-ELISAs ranged from 0% to over 100%, and prevalence differed significantly (P < or = 0.0001) between villages in four of the five districts. Overall, 10% of buffaloes tested in markets were found to be parasitaemic and 39, 56 and 47 % were found positive with the 2G6 Ag-ELISA, IgG ELISA and CATT, respectively. Incidence rates varied according to the test used and ranged from 0.22 (95 % CI: 0.09, 0.44) to 0.44 (95 % CI: 0.24, 0.76), per animal-year at risk, in two villages. The results highlight the importance of using validated diagnostic tests to obtain accurate estimates of prevalence and incidence. These parameters are needed, for example in mathematical models, for the development and evaluation of different control strategies for T. evansi infections in buffaloes.

HTS in the new millennium: the role of pharmacology and flexibility.

Over the past decade, high throughput screening (HTS) has become the focal point for discovery programs within the pharmaceutical industry. The role of this discipline has been and remains the rapid and efficient identification of lead chemical matter within chemical libraries for therapeutics development. Recent advances in molecular and computational biology, i.e., genomic sequencing and bioinformatics, have resulted in the announcement of publication of the first draft of the human genome. While much work remains before a complete and accurate genomic map will be available, there can be no doubt that the number of potential therapeutic intervention points will increase dramatically, thereby increasing the workload of early discovery groups. One current drug discovery paradigm integrates genomics, protein biosciences and HTS in establishing what the authors refer to as the "gene-to-screen" process. Adoption of the "gene-to-screen" paradigm results in a dramatic increase in the efficiency of the process of converting a novel gene coding for a putative enzymatic or receptor function into a robust and pharmacologically relevant high throughput screen. This article details aspects of the identification of lead chemical matter from HTS. Topics discussed include portfolio composition (molecular targets amenable to small molecule drug discovery), screening file content, assay formats and plating densities, and the impact of instrumentation on the ability of HTS to identify lead chemical matter.

Anxiety disorders, comorbidity, and suicide attempts in adolescence: a preliminary investigation.

The prevalence of anxiety disorders and associated DSM-III-R diagnoses were measured in a sample of 80 female adolescents aged between 15 to 20 years consulting an outpatient psychiatric service for adolescents. The suicide attempt group (SA) included 40 patients evaluated within 24 h after attempted suicide. This is compared to 40 consecutive patients consulting the same center but without any history of suicide attempt (the no attempt group, NA). The global prevalence of anxiety disorders was similar in both groups (SA: 65% vs. NA: 60%, NS) as was the relative importance of the different disorders in each group, generalized anxiety being the most frequent specific anxiety disorder. The most striking difference between the two groups was in the prevalence of affective disorders in 90% (SA) vs. 32.5% (NA) (P < 0.001), leading to high rates of comorbidity on axis I in the SA group. Of the 24 patients with anxiety disorders who attempted suicide, 21 (95%) fulfilled criteria for associated major depression, compared to five out of 21 (24%) patients with anxiety disorders who had not attempted suicide. Adolescents with anxiety disorders developing major depression are at a high risk for suicide. The depression may be of short duration (less than two weeks) when compared to that of the anxiety disorder (greater than six months). To improve suicide prevention, our findings if confirmed should encourage clinicians to perform a close follow-up of adolescents with anxiety disorders for an early detection of sudden depressive breakdowns.