Non-zero Level Research Articles

HIV-infection model stabilization

In the paper considers a problem of stabilizing the system of differential equations with delay that described HIV infection dynamics mathematical model. A stabilizing control is constructed basing on the method of explicit solutions of Generalized Riccati Equations of the theory of analytical constructing regulator for systems of functional differential equations. For construct a feedback control we use the second variant of explicit solutions of the generalized Riccati equations. First and third variants of stabilization discussed in other authors articles. To determine the parameters of the stabilization control based on the second variant of explicit solutions of generalized Riccati equation should be found special exponential matrix equation solution. Considered stabilizing control for the system of differential equations with delay leads HIV-infection system to the small non-zero level of infection. Results of the research can be applied to analysis of some aspects of HIV dynamics.

Case Report: Hyponatremia of malignancy – An alternative mechanism? Syndrome of inappropriate atrial natriuretic peptide (SIANP)

Euvolemic hyponatremia in the setting of lung cancer is most commonly due to the syndrome of inappropriate anti-diuretic hormone secretion (SIADH). However, a subset of patients with small cell carcinoma and hyponatremia also have elevated levels of atrial natriuretic peptide (ANP), which is produced by some small cell tumors. We report the case of a 64-year-old man with a limited-stage small cell carcinoma of the lung undergoing chemoradiation therapy, who was admitted to hospital with a pulmonary embolism. Two months earlier, at the time of diagnosis with lung cancer, he had a hypotonic, euvolemic hyponatremia, presumed to be caused by SIADH. At that time, his serum sodium readily normalized with fluid restriction and ADH-antagonist therapy with demeclocycline. However, during his second admission, the hyponatremia was refractory to treatment: his sodium level slowly declined from 138 mmol/L to a nadir of 118 mmol/L, despite early initiation of fluid restriction and maximal doses of demeclocycline. Laboratory values revealed a low but inappropriately non-zero level of ADH but also an inappropriately low level of aldosterone and an elevated level of ANP, suggesting that SIADH might not be the only contributor to the hyponatremia. While a causal link between ectopic ANP production and hyponatremia has never been established, an inappropriately high level of ANP can directly decrease sodium re-absorption in the proximal convoluted tubule of the kidney and increase glomerular filtration rate (GFR), resulting in greater excretion of sodium and water. In addition, high circulating levels of ANP can inhibit aldosterone secretion, potentially resulting in further sodium wasting. Here, the elevated ANP and inappropriately low aldosterone suggested the possibility that the refractory hyponatremia, although initiated by SIADH, was further worsened by an ANP-mediated natriuresis and suppression of aldosterone response.

Lack of divine coincidence in New Keynesian models

The literature has long agreed that the divine coincidence holds in standard New Keynesian models: the monetary authority is able to simultaneously stabilize inflation and output gap in response to preference and technology shocks. I show that the divine coincidence holds only when inflation is stabilized at exactly zero. Even small deviations from zero generate policy trade-offs. I demonstrate this result using the model׳s non-linear equilibrium conditions to avoid biases from log-linearization. When the model is log-linearized, a non-zero steady state level of inflation gives rise to what I call the endogenous trend inflation cost-push shock in the New -Keynesian Phillips curve.

Sa1248 TNF-Responsive Cellular Based Assay Reveals Neutralizing Capacity of Anti-Adalimumab Antibodies in Crohn's Disease and Ulcerative Colitis Patients

Introduction: During infliximab(IFX) therapy for IBD anti-drug antibody formation can lead to loss of response(LOR) to the drug. Data for adalimumab is limited. Karmiris et al.1 demonstrated that adalimumab resulted in sustained clinical benefit in two thirds of Crohn's disease(CD) patients during 2 year follow-up. We performed additional analyses on this cohort using the homogeneous mobility shift assay(HMSA)2, focusing on the inter-relationship of serum concentrations of adalimumab, antibodies-to-adalimumab(ATA) and CRP. Methods: 536 prospectively collected serum samples were available from 148/168 patients in the Karmiris cohort for additional analysis. Serum adalimumab and ATA at pre-defined time points were measured using HMSA. Samples were classified as ATA negative, ATA detectable(non-zero ATA levels below the lower limit of quantitation, LLOQ of 1.7 U/ml) or ATA positive(ATA ≥ LLOQ). The LLOQ for adalimumab was ≥ 1.0 μg/ml. We studied the role of week 4 adalimumab levels on ATA formation with a Cox proportional hazards model of time-to-ATA vs. adalimumab. Repeated measures mixed regression modeling was performed to assess the independent effects of ATA and adalimumab on CRP. Results: ATA were positive(above LLOQ) in 20.2 % of patients (n = 30/148) after a median of 34 weeks(IQR 12.4 60.5 weeks). Samples with adalimumab in the lower two quartiles were more often ATA positive compared to samples in the 3rd and 4th adalimumab quartile(p LLOQ) were associated with lower median adalimumab levels than ATA negative samples(p 5 μg/ml(HR = 11.13, p = 0.0002). Regression modeling showed a negative correlation between CRP and adalimumab levels(p=0.0013) and a positive association with ATA(p=0.042). When the model was used to predict CRP one observation in the future, ATA was strongly associated with future CRP increase (p=0.002; median 7.8 weeks between samples; IQR 4.0 15.8), while adalimumab levels were not(p=0.176). Per-patient median CRP was significantly higher in patients who eventually failed adalimumab therapy (median 8.34 mg/L vs. 4.35 mg/L; p=0.026). Conclusion: Using HMSA, ATA were detected in 20% of patients in this cohort on adalimumab maintenance therapy, compared to 9% as previously reported2. Risk of ATA formation increased with lower early drug levels. Interestingly ATA was strongly associated with CRP in the future while drug levels were only informative of present CRP levels. These data suggest that early drug and antibody level monitoring and subsequent dose optimization would help prevent ATA and improve patient outcomes.

Sa1247 Antibodies to Adalimumab Predict Inflammation in Crohn's Patients on Maintenance Adalimumab Therapy

Introduction: During infliximab(IFX) therapy for IBD anti-drug antibody formation can lead to loss of response(LOR) to the drug. Data for adalimumab is limited. Karmiris et al.1 demonstrated that adalimumab resulted in sustained clinical benefit in two thirds of Crohn's disease(CD) patients during 2 year follow-up. We performed additional analyses on this cohort using the homogeneous mobility shift assay(HMSA)2, focusing on the inter-relationship of serum concentrations of adalimumab, antibodies-to-adalimumab(ATA) and CRP. Methods: 536 prospectively collected serum samples were available from 148/168 patients in the Karmiris cohort for additional analysis. Serum adalimumab and ATA at pre-defined time points were measured using HMSA. Samples were classified as ATA negative, ATA detectable(non-zero ATA levels below the lower limit of quantitation, LLOQ of 1.7 U/ml) or ATA positive(ATA ≥ LLOQ). The LLOQ for adalimumab was ≥ 1.0 μg/ml. We studied the role of week 4 adalimumab levels on ATA formation with a Cox proportional hazards model of time-to-ATA vs. adalimumab. Repeated measures mixed regression modeling was performed to assess the independent effects of ATA and adalimumab on CRP. Results: ATA were positive(above LLOQ) in 20.2 % of patients (n = 30/148) after a median of 34 weeks(IQR 12.4 60.5 weeks). Samples with adalimumab in the lower two quartiles were more often ATA positive compared to samples in the 3rd and 4th adalimumab quartile(p LLOQ) were associated with lower median adalimumab levels than ATA negative samples(p 5 μg/ml(HR = 11.13, p = 0.0002). Regression modeling showed a negative correlation between CRP and adalimumab levels(p=0.0013) and a positive association with ATA(p=0.042). When the model was used to predict CRP one observation in the future, ATA was strongly associated with future CRP increase (p=0.002; median 7.8 weeks between samples; IQR 4.0 15.8), while adalimumab levels were not(p=0.176). Per-patient median CRP was significantly higher in patients who eventually failed adalimumab therapy (median 8.34 mg/L vs. 4.35 mg/L; p=0.026). Conclusion: Using HMSA, ATA were detected in 20% of patients in this cohort on adalimumab maintenance therapy, compared to 9% as previously reported2. Risk of ATA formation increased with lower early drug levels. Interestingly ATA was strongly associated with CRP in the future while drug levels were only informative of present CRP levels. These data suggest that early drug and antibody level monitoring and subsequent dose optimization would help prevent ATA and improve patient outcomes.

Sa1249 Infliximab and Antibody to Infliximab Concentrations in 7,613 Patients Shows Indication for Testing, Association With Loss of Response and Provides New Insights Into Binding Characteristics of Anti-Drug Antibodies

Introduction: During infliximab(IFX) therapy for IBD anti-drug antibody formation can lead to loss of response(LOR) to the drug. Data for adalimumab is limited. Karmiris et al.1 demonstrated that adalimumab resulted in sustained clinical benefit in two thirds of Crohn's disease(CD) patients during 2 year follow-up. We performed additional analyses on this cohort using the homogeneous mobility shift assay(HMSA)2, focusing on the inter-relationship of serum concentrations of adalimumab, antibodies-to-adalimumab(ATA) and CRP. Methods: 536 prospectively collected serum samples were available from 148/168 patients in the Karmiris cohort for additional analysis. Serum adalimumab and ATA at pre-defined time points were measured using HMSA. Samples were classified as ATA negative, ATA detectable(non-zero ATA levels below the lower limit of quantitation, LLOQ of 1.7 U/ml) or ATA positive(ATA ≥ LLOQ). The LLOQ for adalimumab was ≥ 1.0 μg/ml. We studied the role of week 4 adalimumab levels on ATA formation with a Cox proportional hazards model of time-to-ATA vs. adalimumab. Repeated measures mixed regression modeling was performed to assess the independent effects of ATA and adalimumab on CRP. Results: ATA were positive(above LLOQ) in 20.2 % of patients (n = 30/148) after a median of 34 weeks(IQR 12.4 60.5 weeks). Samples with adalimumab in the lower two quartiles were more often ATA positive compared to samples in the 3rd and 4th adalimumab quartile(p LLOQ) were associated with lower median adalimumab levels than ATA negative samples(p 5 μg/ml(HR = 11.13, p = 0.0002). Regression modeling showed a negative correlation between CRP and adalimumab levels(p=0.0013) and a positive association with ATA(p=0.042). When the model was used to predict CRP one observation in the future, ATA was strongly associated with future CRP increase (p=0.002; median 7.8 weeks between samples; IQR 4.0 15.8), while adalimumab levels were not(p=0.176). Per-patient median CRP was significantly higher in patients who eventually failed adalimumab therapy (median 8.34 mg/L vs. 4.35 mg/L; p=0.026). Conclusion: Using HMSA, ATA were detected in 20% of patients in this cohort on adalimumab maintenance therapy, compared to 9% as previously reported2. Risk of ATA formation increased with lower early drug levels. Interestingly ATA was strongly associated with CRP in the future while drug levels were only informative of present CRP levels. These data suggest that early drug and antibody level monitoring and subsequent dose optimization would help prevent ATA and improve patient outcomes.

Free Field Realizations of Induced Modules for Affine Lie Algebras

We construct a free field realization of generalized loop modules induced from admissible diagonal ℤ-graded irreducible modules of nonzero level for a Heisenberg subalgebra of untwisted affine Lie algebra of type A. Such generalized loop modules are irreducible as it was shown in Bekkert et al. [2]. We also extend this construction to modules induced from an arbitrary parabolic subalgebra of whose Levi factor is infinite-dimensional and contains .

Some Consequences of Zero Point Energy

Both theory and experiments indicate that the vacuum is not a state of empty space, but is populated by electromagnetic fluctuations at a lowest nonzero level, the Zero Point Energy (ZPE). This debouches into considerable changes of fundamental physics, as shown by a revised quantum electrodynamic theory (RQED) applied to elementary particles, and by a revised ZPE frequency spectrum applied to the expanding universe. The Standard Model based on a vacuum state of empty space is thus replaced by RQED, thereby resulting in massive elementary particles from the beginning, independently of the theory by Higgs. Also the basic properties of the Higgs-like particle detected at CERN can be reproduced by RQED. It further leads to new fundamental results beyond the theories by Dirac and Higgs, such as to a deduced value of the elementary net charge, magnetic confinement of charged particle configurations, intrinsic local particle charges, photon spin with a very small but nonzero photon rest mass, and needle-like particle-wave properties which contribute to the understanding of the photoelectric effect and two-slit experiments. The real macroscopic pressure due to the revised ZPE frequency distribution further influences the dynamics of the expanding universe, by the ZPE photon pressure gradient acting as dark energy, and the ZPE photon energy density acting as dark matter. This results in a model being consistent with the observed scale, the rate of expansion, and the stability of a flat expanding observable universe.

Simultaneous confidence bounds in monotone dose–response studies

In dose–response studies, one of the most important issues is the identification of minimum effective dose (MED), where the MED is defined as the lowest dose such that the mean response is better than the mean response of a zero-dose control by a clinically significant difference. Dose–response curves are sometimes monotonic in nature. In this paper, we propose a new method to construct simultaneous confidence lower bounds for the differences between the mean response of any non-zero dose level and that of the control under the monotonicity assumption to identify the MED. The evaluation of the lower confidence bounds is a concave programming problem subject to homogeneous linear inequality constraints. A necessary and sufficient condition for the solution and its simplified expressions are derived. An efficient computing algorithm is proposed. A real data example from a dose–response study is used to illustrate the method.

Prevalence and Correlates of Pain and Pain Treatment in a Western Kenya Referral Hospital

Pain is often inadequately evaluated and treated in sub-Saharan Africa (SSA). We sought to assess pain levels and pain treatment in 400 hospitalized patients at a national referral hospital in western Kenya, and to identify factors associated with pain and pain treatment. Using face-validated Kiswahili versions of two single-item pain assessment tools, the Numerical Rating Scale (NRS) and the Faces Pain Scale-Revised (FPS-R), we determined patients' pain levels. Additional data collected included patient demographics, prescribed analgesics, and administered analgesics. We calculated mean pain ratings and pain management index (PMI) scores. Averaged between the NRS and FPS-R, 80.5% of patients endorsed a nonzero level of pain and 30% of patients reported moderate to severe pain. Older patients, patients with HIV, and cancer patients had higher pain ratings. Sixty-six percent of patients had been prescribed analgesics at some point during their hospitalization, the majority of which were nonopioids. A majority of patients (66%) had undertreated pain (negative scores on the PMI). This study shows that hospitalized patients in Kenya are experiencing pain and that this pain is often undertreated.

Interactive Diffusions for Global Optimization

We present a novel approach, in which parallel annealing processes interact in a manner that expedites the identification of a globally optimal solution. A first annealing process operates at a faster time scale and has a drift function that converges to a non-zero (but relatively small) noise level. A second annealing process (operating at a slower time scale) is subject to a modified drift term in which the steepest descent direction is perturbed with the first annealing process density gradient. This additional term ensures that the second process is "repelled" from regions already explored. As a result, the first annealing process (which quickly identifies locally optimal solutions) allows the second annealing process to bypass locally optimal solutions recently identified, so that it can be made to converge to global optima at a faster rate. We show that, when compared to independent annealing processes, the proposed interactive diffusions can increase the speed of convergence at the expense of minimal additional computational overhead.

Uncertainty due to low‐dose extrapolation: modified BMD methodology for epidemiological data

Traditional environmental risk assessment methodologies, including benchmark dose (BMD) estimation, were originally developed to be used with animal toxicology data. We discuss some problems that can occur when toxicology‐based methods are applied to human cohort studies, and we propose a new method for BMD risk estimation adapted to epidemiological data. Instead of extrapolating to zero‐dose levels to estimate risk in an unexposed population, our proposed alternative involves specifying a nonzero background exposure level instead. To account for uncertainty in that level, we can average modified BMDs over a distribution of exposure levels. We apply our modified BMD method to analyze data from a cohort study designed to assess the effects of prenatal polychlorinated biphenyl (PCB) exposure on cognitive ability in young children. Copyright © 2013 John Wiley & Sons, Ltd.

Representations of the twisted affine Nappi-Witten algebras

In this paper, we study Verma modules for the twisted affine Nappi-Witten algebras \documentclass[12pt]{minimal}\begin{document}$\widehat{H}_{4}[\tau _{1}]$\end{document}Ĥ4[τ1] and \documentclass[12pt]{minimal}\begin{document}$\widehat{H}_{4}[\tau _{2}]$\end{document}Ĥ4[τ2]. The vertex operator representations of the affine Nappi-Witten algebras \documentclass[12pt]{minimal}\begin{document}$\widehat{H}_{4}[\tau _{1}]$\end{document}Ĥ4[τ1], \documentclass[12pt]{minimal}\begin{document}$\widehat{H}_{4}[\tau _{2}]$\end{document}Ĥ4[τ2], and \documentclass[12pt]{minimal}\begin{document}$\widehat{H}_{4}$\end{document}Ĥ4 are also constructed. Furthermore, the irreducible non-zero level quasifinite modules over the affine Nappi-Witten algebras are classified.

Actuarial Assessment of Fatalities Attributable to CCS in 2050

We estimated the human cost of failures in the CCS industry in 2050, using the actuarial approach. The range of expected fatalities is assessed integrating all steps of the CCS chain: additional coal production, coal transportation, carbon capture, transport, injection and storage, based on empirical evidence from technical or social analogues. The main finding is that a few hundred fatalities per year should be expected if the technology is used to avoid emitting 3.67 GtCO2 yr-1 in 2050 at baseload coal power plants. The large majority of fatalities are attributable to mining and delivering more coal. These risks compare to today's industrial hazards: technical, knowable and occupational dangers for which there are socially acceptable non-zero risk levels. Some contemporary European societies tolerate about one fatality per thousand year around industrial installations. If storage sites perform like that, then expected fatalities per year due to leakage should have a minor contribution in the total expected fatalities per year: less than one. But to statistically validate such a safety level, reliability theory and the technology roadmap suggest that CO2 storage demonstration projects over the next 20 years have to cause exactly zero fatality.

Differential Distribution of Activated Innate and Adaptive Immune Subsets in G-CSF Mobilized Hematopoietic Stem Cell Allografts May Influence Incidence of Acute (aGVHD) and Chronic Graft-Versus-Host Disease (cGVHD)

AbstractAbstract 4192Donor T cells are known to be the most powerful effectors for GVHD. Recently, the dose of invariant NKT and B cells in the allograft have been associated with incidence of aGVHD in sibling transplants (Chaidos et al, Blood 2012; Michonneau et al, Brit.J.Hem 2009). Murine models suggest a role for donor B cells and CD4+ T cells in development of cGVHD (Young et al, J.Immunol 2012). The influence of NK cells, NKT cells, B cells in allografts from matched unrelated donor (MUD) transplants on incidence of cGVHD is unknown. Here we present results on influence of innate and adaptive immune subsets in the allograft and the incidence of aGVHD and cGVHD in 108 patients (pts). We analyzed the absolute numbers of T, NK, NKT and B cells along with extensive immunophenotypic characterization of their activation status in consecutive allografts obtained from both sibling and MUD between 2010– 2011. All allografts were peripheral blood stem cells mobilized after 5 days of G-CSF administration. Of the 108 pts, 67 pts received grafts from MUD; 71 pts had received a reduced-intensity conditioning regimen. All pts receiving allografts from MUD received anti-thymocyte globulin. Median age of pts at transplant was 55 years (21–73 years). Median CD34+ dose was 6.51 x106/kg and median CD3+ dose was 2.33 x108/kg. The incidence of aGVHD and cGVHD was 58% and 38% respectively. We compared in an unsupervised approach whether absolute numbers of resting and activated NK, NKT, B, CD4+ and CD8+ T cells were different in pts with vs. without aGVHD/cGVHD. Univariate logistic regression models and Wilcoxon rank sum tests were used to assess differential expression of absolute and percent immune subset markers between those who did vs. did not develop GVHD, analyzing separately for aGVHD and cGVHD. In addition, some markers had a number of absolute values of zero, where the parameter of interest was whether or not a donor had a non-zero value and its association with GVHD in pts. Results:Median numbers of activated NK cells (CD3−CD56+CD16+CD69+) cells were significantly higher in pts with vs. without aGVHD (586.4/μL vs. 270.5/μl, p=0.003). Higher median numbers of resting NK cells (CD3−CD56+CD16+) and activated B cells (CD19+CD80+) were associated with cGVHD but not aGVHD. Non-zero levels of CD4+ T cells expressing prostaglandin D2 (PGD2) receptor (CD4+CD294+), chemokine receptor CCR3 (CD4+CD193+), chemokine receptor 4 CCR4 (CD4+CD194+) and CXCR3 (CD4+CD183+) in the allograft were associated with lower incidence of cGVHD. Also CD4+ T cells expressing both CCR4 and PGD2 receptors were associated with lower incidence of cGVHD. Significant differences were seen in median numbers (Table 1) and % of non-zero values (Table 2) of NK cells, B cells, and activated CD4+ T cells between those who did vs. did not develop cGVHD. Immunophenotypic analyses of pts receiving these allografts at days 30 and 100 post transplant were also performed. Updated results about correlation of these subsets between allografts and post-transplant patient samples will be presented. Multivariate analyses of these subsets in conjunction with clinical factors are being performed. In conclusion, activated B cells in the allograft may influence the incidence of cGVHD; in particular B cells expressing CD80, a co-stimulatory molecule for T cells and their association with cGVHD confirms results from murine models. Interestingly, CD4+ T cells associated with lower incidence of cGVHD expressed receptors for chemokines, CXCR3 and prostaglandin D2. These homing receptors are up regulated selectively in CD4+ T cells in the absence of chronic GVHD, suggesting a protective role for these receptors in the pathogenesis of cGVHD. Activated and resting NK cells were also associated with acute and chronic GVHD respectively. These results showing an association of specific immune subsets in the allograft and GVHD may provide opportunities for therapeutic interventions for graft engineering.Table 1Median absolute numbers of NK and B cells by cGVHD statusSubsetcGVHDNo cGVHDp-valueCD3−/CD56+/CD16+/CD117−636148920.036CD19+/CD80+109.671.20.012Table 2Percent with non-zero absolute numbers of activated CD4+ T cells by cGVHD statusSubset% non-zero values in pts without cGVHD% non-zero values in pts with cGVHDp-valueCD4+/CD193+27.9%5.1%0.004CD4+/CD294+41.0%10.3%0.0013CD4+/CD183+41.0%10.3%0.0007CD4+/CD194+42.6%10.3%0.0006CD4+/CD294+/CD194+36.1%7.7%0.0017 Disclosures:Off Label Use: Lenalidomide in AML. Jaglowski:Pharmacyclics: Research Funding. Benson:Innate Pharma: Research Funding. Devine:Sanofi: Honoraria, Research Funding.

A stochastic model of the logistics actions required to ensure the availability of spare parts during maintenance of railway vehicles

Models that can predict the correct logistics actions that need to be taken to ensure the availability of spare parts during maintenance of railway vehicles are of considerable interest. Since the occurrence of defects is a random phenomenon it is not possible to know in advance what spare parts will be required at any point in time. This situation requires the creation of a stochastic model that can incorporate uncertainty. Deterministic and stochastic models of maintenance logistics are based on the assumption of a non-zero stock level of spare parts. Carrying an extensive inventory of parts requires a large financial outlay and it is still often the case that a required spare part is not immediately available and has to be obtained. This paper shows, provided certain conditions are met, that it is possible to create cost-effective maintenance procedures even if the required spare part is not immediately available. Thus, the amount of money locked up in stock can be effectively regulated, thus reducing operating costs.

New irreducible modules for Heisenberg and affine Lie algebras

We study Z-graded modules of nonzero level with arbitrary weight multiplicities over Heisenberg Lie algebras and the associated generalized loop modules over affine Kac–Moody Lie algebras. We construct new families of such irreducible modules over Heisenberg Lie algebras. Our main result establishes the irreducibility of the corresponding generalized loop modules providing an explicit construction of many new examples of irreducible modules for affine Lie algebras. In particular, to any function φ:N→{±} we associate a φ-highest weight module over the Heisenberg Lie algebra and a φ-imaginary Verma module over the affine Lie algebra. We show that any φ-imaginary Verma module of nonzero level is irreducible.

MaximalCPand bounds on the neutron electric dipole moment fromPandCPbreaking

We find in theories with spontaneous P and CP violation that symmetries needed to set the tree level strong CP phase to zero can also set all non-zero tree level CP violating phases to the maximal value \pi / 2 in the symmetry basis simultaneously explaining the smallness of \bar{\theta} and the largeness of the CKM CP violating phase. In these models we find the one loop lower bound \bar{\theta} > 10^{-11} relevant for early discovery of neutron edm d_n > 10^{-27} ecm. The lower bound relaxes to \bar{\theta} > 10^{-13} or d_n > 10^{-29} ecm for the case where the CP phases are non-maximal. Interestingly the spontaneous CP phase appears in the quark sector, not the Higgs sector, and is enabled by a heavy left-right symmetric vectorlike quark family with mass M. These results do not vanish in the decoupling limit of M_{H_2^+} > M \rightarrow \infty (where M_{H_2^+} is the mass of heavy Higgs at the parity breaking scale) and the age-old expectation that laws of nature (or its Lagrangian) are parity and matter-antimatter symmetric may be testable by the above predictions and EDM experiments, even if new physics occurs only at see-saw, GUT or Planck scales. There is also a region in parameter space with M_{H_2^+} < M where the above bounds are dampened by the factor (M_{H_2^+}/M)^2. By using flavour symmetries and texture arguments we also make predictions for the CKM phase that arises from the maximal phase on diagonalization to the physical basis. There are no axions predicted in this model.

Organophosphate pesticide levels in blood and urine of women and newborns living in an agricultural community

Organophosphate pesticides are widely used and recent studies suggest associations of in utero exposures with adverse birth outcomes and neurodevelopment. Few studies have characterized organophosphate pesticides in human plasma or established how these levels correlate to urinary measurements. We measured organophosphate pesticide metabolites in maternal urine and chlorpyrifos and diazinon in maternal and cord plasma of subjects living in an agricultural area to compare levels in two different biological matrices. We also determined paraoxonase 1 (PON1) genotypes (PON1192 and PON1−108) and PON1 substrate-specific activities in mothers and their newborns to examine whether PON1 may affect organophosphate pesticide measurements in blood and urine.Chlorpyrifos levels in plasma ranged from 0–1726ng/mL and non-zero levels were measured in 70.5% and 87.5% of maternal and cord samples, respectively. Diazinon levels were lower (0–0.5ng/mL); non-zero levels were found in 33.3% of maternal plasma and 47.3% of cord plasma. Significant associations between organophosphate pesticide levels in blood and metabolite levels in urine were limited to models adjusting for PON1 levels. Increased maternal PON1 levels were associated with decreased odds of chlorpyrifos and diazinon detection (odds ratio(OR): 0.56 and 0.75, respectively). Blood organophosphate pesticide levels of study participants were similar in mothers and newborns and slightly higher than those reported in other populations. However, compared to their mothers, newborns have much lower quantities of the detoxifying PON1 enzyme suggesting that infants may be especially vulnerable to organophosphate pesticide exposures.

Predicting the probability of persistence of HIV infection with the standard model

We consider the standard three-component differential equation model for the growth of an HIV virion population in an infected host in the absence of drug therapy. The dynamical properties of the model are determined by the set of values of six parameters which vary across host populations. There may be one or two critical points whose natures play a key role in determining the outcome of infection and in particular whether the HIV population will persist or become extinct. There are two cases which may arise. In the first case, there is only one critical point P_1 at biological values and this is an asymptotically stable node. The system ends up with zero virions and so the host becomes HIV-free. In the second case, there are two critical points P_1 and P_2 at biological values. Here P_1 is an unstable saddle point and P_2 is an asymptotically stable spiral point with a non-zero virion level. In this case the HIV population persists unless parameters change. We let the parameter values take random values from distributions based on empirical data, but suitably truncated, and determine the probabilities of occurrence of the various combinations of critical points. From these simulations the probability that an HIV infection will persist, across a population, is estimated. It is found that with conservatively estimated distributions of parameters, within the framework of the standard 3-component model, the chances that a within host HIV population will become extinct is between 0.6% and 6.9%. With less conservative parameter estimates, the probability is estimated to be as high as 24%. The many factors related to the transmission and possible spontaneous elimination of the virus are discussed.