Surgery-Guided Removal of Ovarian Cancer Using Up-Converting Nanoparticles

Ovarian cancer survival and the recurrence rate are drastically affected by the amount of tumor that can be surgically removed prior to chemotherapy. Surgeons are currently limited to visual inspection, making smaller tumors difficult to be removed surgically. Enhancing the surgeon’s ability to selectively remove cancerous tissue would have a positive effect on a patient’s prognosis. One approach to aid in surgical tumor removal involves using targeted fluorescent probes to selectively label cancerous tissue. To date, there has been a trade-off in balancing two requirements for the surgeon: the ability to see maximal tumors and the ability to identify these tumors by eye while performing the surgery. The ability to see maximal tumors has been prioritized and this has led to the use of fluorophores activated by near-infrared (NIR) light as NIR penetrates most deeply in this surgical setting, but the light emitted by traditional NIR fluorophores is invisible to the naked eye. This has necessitated the use of specialty detectors and monitors that the surgeon must consult while performing the surgery. In this study, we develop nanoparticles that selectively label ovarian tumors and are activated by NIR light but emit visible light. This potentially allows for maximal tumor observation and real-time detection by eye during surgery. We designed two generations of up-converting nanoparticles that emit green light when illuminated with NIR light. These particles specifically label ovarian tumors most likely via tumor-associated macrophages, which are prominent in the tumor microenvironment. Our results demonstrate that this approach is a viable means of visualizing tumors during surgery without the need for complicated, expensive, and bulky detection equipment. Continued improvement and experimentation could expand our approach into a much needed surgical technique to aid ovarian tumor removal

Higgs-boson production associated with a bottom quark at hadron colliders with SUSY-QCD corrections

The Higgs boson production p p (p\bar p) -> b h +X via b g -> b h at the LHC, which may be an important channel for testing the bottom quark Yukawa coupling, is subject to large supersymmetric quantum corrections. In this work the one-loop SUSY-QCD corrections to this process are evaluated and are found to be quite sizable in some parameter space. We also study the behavior of the corrections in the limit of heavy SUSY masses and find the remnant effects of SUSY-QCD. These remnant effects, which are left over in the Higgs sector by the heavy sparticles, are found to be so sizable (for a light CP-odd Higgs and large \tan\beta) that they might be observable in the future LHC experiment. The exploration of such remnant effects is important for probing SUSY, especially in case that the sparticles are too heavy (above TeV) to be directly discovered at the LHC.Comment: Results for the Tevatron adde

A New Model for Fermion Masses in Supersymmetric Grand Unified Theories

We present a simple model for fermion mass matrices and quark mixing in the context of supersymmetric grand unified theories and show its agreement with experiment. Our model realizes the GUT mass relations $m_d=3m_e$, $m_s= m_\mu/3$, $m_b=m_\tau$ in a new way and is easily consistent with values of $m_t$ suggested by MSSM fits to LEP data.Comment: Latex, 8 p., ITP-SB-93-37 (revised version contains minor changes in some wording and citations; no changes in analytic or numerical results.

Supersymmetric Electroweak Corrections to Single Top Quark Production at the Fermilab Tevatron

We have calculated the $O(\alpha_{ew} M_t^2/M_W^2)$ supersymmetric electroweak corrections to single top quark production via $q\bar q' \to t\bar b$ at the Fermilab Tevatron in the minimal supersymmetric model. The supersymmetric electroweak corrections to the cross section are a few percent for $tan \beta> 1$, and can exceed 10% for $tan\beta<1$. The combined effects of SUSY electroweak corrections and the Yukawa corrections can exceed 10% for favorable parameter values, which might be observable at a high-luminosity Tevatron.Comment: 13 pages, 4 figures available at reques

Moderate Supersymmetric CP Violation

It is well known that supersymmetry (SUSY) gives neutron and electron electric dipole moments ($d_n$ and $d_e$) which are too large by about $10^{3}$. If we assume a SUSY model cannot contain fine-tunings or large mass scales, then one must require that the SUSY breaking mechanism give real soft breaking parameters, in which case the minimal SUSY model has no $CP$ violation other than from the CKM matrix (besides possible strong $CP$ violating effects). We show that in non-minimal SUSY models, a moderate amount of $CP$ violation can be induced through one loop corrections to the scalar potential, giving an effective phase of order $10^{-3}$, and thus implying $d_n$ and $d_e$ can be near their current experimental bounds $naturally$. This moderate amount of SUSY $CP$ violation could also prove important for models of electroweak baryogenesis. We illustrate our results with a specific model.Comment: 19pp plain LATEX, 1 fig (by EMAIL request), TRI-PP-93-86. (Some clarifying comments about renormalizability added--version to appear in Phys. Rev. D

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

&lt;b&gt;Objective&lt;/b&gt; &lt;i&gt;ABCB1&lt;/i&gt; encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; The best candidates from fine-mapping analysis of 21 &lt;i&gt;ABCB1&lt;/i&gt; SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt; Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, &lt;i&gt;ABCB1&lt;/i&gt; expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; Our study represents the largest analysis of &lt;i&gt;ABCB1&lt;/i&gt; SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.&lt;p&gt;&lt;/p&gt

Single top quark production as a probe of R-parity-violating SUSY at pp and p\bar p colliders

We investigate the ability of single top quark production via qq'-> squark->tb and q \bar q'->slepton->t\bar b at the LHC and Tevatron to probe the strength of R-parity violating couplings in the minimal supersymmetric model. We found that given the existing bounds on R-parity violating couplings, single top quark production may be greatly enhanced over that predicted by the standard model, and that both colliders can either discover R-parity violating SUSY or set strong constraints on the relevant R-parity violating couplings. We further found that the LHC is much more powerful than the Tevatron in probing the squark couplings, but the two colliders have comparable sensitivity for the slepton couplings.Comment: 15 pages, 4 figure

Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study

OBJECTIVES: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. STUDY DESIGN: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ2 analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. RESULTS: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P < .04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P = .001) and ascites (OR, 2.89; P = .01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P < .02) and mental/cognitive/language impairment (OR, 4.76; P = .02) at 2 years of age. CONCLUSION: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions

Supersymmetric effects in top quark decay into polarized W-boson

We investigate the one-loop supersymmetric QCD (SUSY-QCD) and electroweak (SUSY-EW) corrections to the top quark decay into a b-quark and a longitudinal or transverse W-boson. The corrections are presented in terms of the longitudinal ratio \Gamma(t-->W_L b)/\Gamma(t--> W b) and the transverse ratio \Gamma(t-->W_- b)/\Gamma(t--> W b). In most of the parameter space, both SUSY-QCD and SUSY-EW corrections to these ratios are found to be less than 1% in magnitude and they tend to have opposite signs. The corrections to the total width \Gamma(t-->W b) are also presented for comparison with the existing results in the literature. We find that our SUSY-EW corrections to the total width differ significantly from previous studies: the previous studies give a large correction of more than 10% in magnitude for a large part of the parameter space while our results reach only few percent at most.Comment: Version in PRD (explanation and refs added

Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia

OBJECTIVES: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. STUDY DESIGN: Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). CONCLUSIONS: Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes