Eigenvalue Estimation of Differential Operators

We demonstrate how linear differential operators could be emulated by a quantum processor, should one ever be built, using the Abrams-Lloyd algorithm. Given a linear differential operator of order 2S, acting on functions psi(x_1,x_2,...,x_D) with D arguments, the computational cost required to estimate a low order eigenvalue to accuracy Theta(1/N^2) is Theta((2(S+1)(1+1/nu)+D)log N) qubits and O(N^{2(S+1)(1+1/nu)} (D log N)^c) gate operations, where N is the number of points to which each argument is discretized, nu and c are implementation dependent constants of O(1). Optimal classical methods require Theta(N^D) bits and Omega(N^D) gate operations to perform the same eigenvalue estimation. The Abrams-Lloyd algorithm thereby leads to exponential reduction in memory and polynomial reduction in gate operations, provided the domain has sufficiently large dimension D > 2(S+1)(1+1/nu). In the case of Schrodinger's equation, ground state energy estimation of two or more particles can in principle be performed with fewer quantum mechanical gates than classical gates.Comment: significant content revisions: more algorithm details and brief analysis of convergenc

Epidemiology of Barrett’s Esophagus and Esophageal Adenocarcinoma

Barrett’s esophagus (BE) is a common condition, and is the precursor to esophageal adenocarcinoma, a disease with increasing burden in the western world, especially in Caucasian males. The incidence of BE increased dramatically during the late-20th century and incidence estimates continue to increase, with a prominent male:female ratio. The prevalence is between 0.5 – 2.0 percent. A number of anthropomorphic and behavioral risk factors exist for BE including obesity and tobacco smoking, but GERD is the strongest risk factor, and the risk is more pronounced with long-standing GERD. Esophageal adenocarcinoma (EAC) is the most common form of esophageal cancer in the U.S. Risk factors include GERD, tobacco smoking, and obesity, while NSAIDs and statins may be protective. A major factor predicting progression from non-dysplastic BE to EAC is the presence of dysplastic changes seen on esophageal histology, although a number of issues limit the utility of dysplasia as a marker for disease. Length of the involved BE segment is another risk for progression to high-grade dysplasia and cancer. Biomarkers have shown promise, but none are approved for clinical use

Placing a Price on Medical Device Innovation: The Example of Total Knee Arthroplasty

Background: Total knee arthroplasty (TKA) is common, effective, and cost-effective. Innovative implants promising reduced long-term failure at increased cost are under continual development. We sought to define the implant cost and performance thresholds under which innovative TKA implants are cost-effective. Methods: We performed a cost-effectiveness analysis using a validated, published computer simulation model of knee osteoarthritis. Model inputs were derived using published literature, Medicare claims, and National Health and Nutrition Examination Survey data. We compared projected TKA implant survival, quality-adjusted life expectancy (QALE), lifetime costs, and cost-effectiveness (incremental cost-effectiveness ratios or ICERs) of standard versus innovative TKA implants. We assumed innovative implants offered 5–70% decreased long-term TKA failure rates at costs 20–400% increased above standard implants. We examined the impact of patient age, comorbidity, and potential increases in short-term failure on innovative implant cost-effectiveness. Results: Implants offering ≥50% decrease in long-term TKA failure at ≤50% increased cost offered ICERs <$100,000 regardless of age or baseline comorbidity. An implant offering a 20$150,000 per QALY gained only among healthy 50–59-year-olds. Increasing short-term failure, consistent with recent device failures, reduced cost-effectiveness across all groups. Increasing the baseline likelihood of long-term TKA failure among younger, healthier and more active individuals further enhanced innovative implant cost-effectiveness among younger patients. Conclusions: Innovative implants must decrease actual TKA failure, not just radiographic wear, by 50–55% or more over standard implants to be broadly cost-effective. Comorbidity and remaining life span significantly affect innovative implant cost-effectiveness and should be considered in the development, approval and implementation of novel technologies, particularly in orthopedics. Model-based evaluations such as this offer valuable, unique insights for evaluating technological innovation in medical devices

Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism

Copy number variation (CNV) is a potential contributing factor to many genetic diseases. Here we investigated the potential association of CNV with nonsyndromic cryptorchidism, the most common male congenital genitourinary defect, in a Caucasian population

Anaphylaxis related to avocado ingestion: a case and review

Anaphylaxis to avocado, independent of latex sensitization, has been rarely reported in the literature. This case report describes a 15 year old male who experienced anaphylaxis within half an hour after eating avocado-containing food. Avocado consumption is common in both North America and South America. It is important to consider avocado as a cause of anaphylaxis, even in patients not sensitized to latex

Low Rates of Mother-to-Child HIV Transmission in a Routine Programmatic Setting in Lilongwe, Malawi

Background The Tingathe program utilizes community health workers to improve prevention of mother-to-child transmission (PMTCT) service delivery. We evaluated the impact of antiretroviral (ARV) regimen and maternal CD4+ count on HIV transmission within the Tingathe program in Lilongwe, Malawi. Methods We reviewed clinical records of 1088 mother-infant pairs enrolled from March 2009 to March 2011 who completed follow-up to first DNA PCR. Eligibility for antiretroviral treatment (ART) was determined by CD4+ cell count (CD4+) for women not yet on ART. ART-eligible women initiated stavudine-lamivudine-nevirapine. Early ART was defined as ART for ≥14 weeks prior to delivery. For women ineligible for ART, optimal ARV prophylaxis was maternal AZT ≥6 weeks+sdNVP, and infant sdNVP+AZT for 1 week. HIV transmission rates were determined for ARV regimens, and factors associated with vertical transmission were identified using bivariate logistic regression. Results Transmission rate at first PCR was 4.1%. Pairs receiving suboptimal ARV prophylaxis were more likely to transmit HIV (10.3%, 95% CI, 5.5–18.1%). ART was associated with reduced transmission (1.4%, 95% CI, 0.6–3.0%), with early ART associated with decreased transmission (no transmission), compared to all other treatment groups (p = 0.001). No association was detected between transmission and CD4+ categories (p = 0.337), trimester of pregnancy at enrollment (p = 0.100), or maternal age (p = 0.164). Conclusion Low rates of MTCT of HIV are possible in resource-constrained settings under routine programmatic conditions. No transmissions were observed among women on ART for more than 14 weeks prior to delivery

Phase I Study of Cetuximab, Irinotecan, and Vandetanib (ZD6474) as Therapy for Patients with Previously Treated Metastastic Colorectal Cancer

BACKGROUND: To determine the maximum tolerated dose (MTD) and safety, and explore efficacy and biomarkers of vandetanib with cetuximab and irinotecan in second-line metastatic colorectal cancer. METHODS: Vandetanib (an orally bioavailable VEGFR-2 and EGFR tyrosine kinases inhibitor) was combined at 100 mg, 200 mg, or 300 mg daily with standard dosed cetuximab and irinotecan (3+3 dose-escalation design). Ten patients were treated at the MTD and plasma angiogenesis biomarkers (VEGF, PlGF, bFGF, sVEGFR1, sVEGFR2, IL-1β, IL-6, IL-8, TNF-α, SDF1α) were measured before and after treatment. RESULTS: Twenty-seven patients were enrolled at 4 dose levels and the MTD. Two dose-limiting toxicities (grade 3 QTc prolongation and diarrhea) were detected at 300 mg of vandetanib with cetuximab and irinotecan resulting in 200 mg being the MTD. Seven percent of patients had a partial response, 59% stable disease and 34% progressed. Median progression-free survival was 3.6 months (95% CI, 3.2-5.6) and median overall survival was 10.5 months (95% CI, 5.1-20.7). Toxicities were fairly manageable with grade 3 or 4 diarrhea being most prominent (30%). Vandetanib and cetuximab treatment induced a sustained increase in plasma PlGF and a transient decrease in plasma sVEGFR1, but no changes in plasma VEGF and sVEGFR2. CONCLUSIONS: Vandetanib can be safely combined with cetuximab and irinotecan for metastatic colorectal cancer. Exploratory biomarker analyses suggest differential effects on certain plasma biomarkers for VEGFR inhibition when combined with EGFR blockade and a potential correlation between baseline sVEGFR1 and response. However, while the primary endpoint was safety, the observed efficacy raises concern for moving forward with this combination. TRIAL REGISTRATION: Clinicaltrials.gov NCT00436072