Rodeo Algorithm for Quantum Computing.

We present a stochastic quantum computing algorithm that can prepare any eigenvector of a quantum Hamiltonian within a selected energy interval [E-ε,E+ε]. In order to reduce the spectral weight of all other eigenvectors by a suppression factor δ, the required computational effort scales as O[|logδ|/(pε)], where p is the squared overlap of the initial state with the target eigenvector. The method, which we call the rodeo algorithm, uses auxiliary qubits to control the time evolution of the Hamiltonian minus some tunable parameter E. With each auxiliary qubit measurement, the amplitudes of the eigenvectors are multiplied by a stochastic factor that depends on the proximity of their energy to E. In this manner, we converge to the target eigenvector with exponential accuracy in the number of measurements. In addition to preparing eigenvectors, the method can also compute the full spectrum of the Hamiltonian. We illustrate the performance with several examples. For energy eigenvalue determination with error ε, the computational scaling is O[(logε)^{2}/(pε)]. For eigenstate preparation, the computational scaling is O(logΔ/p), where Δ is the magnitude of the orthogonal component of the residual vector. The speed for eigenstate preparation is exponentially faster than that for phase estimation or adiabatic evolution.

Optimization of microorganism preservation conditions for the development of an acute toxicity bioassay for biocides.

Biocides, also referred to as 'microbicides' or 'inhibitors', are widely used in industrial processes (e.g. utility water in cooling towers) to control and/or eliminate the growth of microorganisms. Because of their inherent toxicity, their presence in various sources (e.g. river sediments, potable water) can negatively affect ecosystems. Currently available biocide detection techniques are not suitable for 'point-of-use' applications since they are tedious, complicated, and often require experienced personnel to operate. To address this concern, we sought to develop a simple-to-use toxicity bioassay based on a model microorganism (E. coli) after short (<30 min) exposure to known biocides that can be stored at room temperature (preferably) or in the fridge. Based on recent work and our expertise in polymer-based preservation of biomolecules, we leveraged this knowledge to improve E. coli preservation for biocide detection purposes. A design-of-experiments strategy was used to evaluate 16 different preservation conditions from 5 process parameters (i.e. 25-1 fractional factorial). It was found that pullulan, a sugar-based polymer, improved E. coli culturability by an order of magnitude after three months of storage. Also, it was found that storing E. coli in the fridge in Milli-Q water was favorable for maintaining a high level of culturability. Finally, the toxicity of three common biocides (Cetyltrimethylammonium bromide (CTAB), ProClin™ 300, and Grotan® BK) was evaluated using a fluorescence-based assay across all 16 preservation conditions. The response of the preserved E. coli was biocide specific and at certain conditions did not vary during the entire three-month storage period.

3D shape evolution of microparticles and 3D enabled applications using non-uniform UV flow lithography (NUFL).

The generation of microparticles with non-spherical morphologies has generated extensive interest because of their enhanced physical properties that can increase their performance in a wide variety of clinical and industrial applications. A flow lithographic technique based on stop flow lithography (SFL) recently showed the ability to fabricate particles with 3D shapes via manipulation of the UV intensity profile in a simple 2D microfluidic channel. Here, we further explore this flow lithographic method, called non-uniform flow lithography (NUFL), to investigate the 3D-shape tuning ability for the generation of 3D magnetic microparticles and their potential applications. We characterize the morphological microparticle shape change through variation of polymerization objective, UV intensity, and solution opacity. We also couple the particles' intrinsic anisotropic magnetic properties with an external magnetic field to create chains of bullet- and bell-shaped particles and a valve-like micromachine. In addition, in contrast to other complex and multi-step methodologies, NUFL shows a simple route for the facile creation of 3D microstructure platforms such as microneedles with fully modifiable tip morphology. This method presents intriguing possibilities for growing research within 3D microstructure assembly, micromachine systems and minimally invasive medical interventions.

Pathway to dry skin prevention and treatment.

BACKGROUND: This article presents an evidence-supported clinical pathway for dry skin prevention and treatment. OBJECTIVE: The development of the pathway involved the following: a literature review was conducted and demonstrated that literature on dry skin is scarce. To compensate for the gap in the available literature, a modified Delphi method was used to collect information on prevention and treatment practice through a panel, which included 10 selected dermatologists who currently provide medical care for dermatology patients in Ontario. An advisor experienced in this therapeutic area guided the process, including a central meeting. Panel members completed a questionnaire regarding their individual practice in caring for these patients and responded to questions on assessment of dry skin etiology, frequency of skin care visits for consultation and follow-up, assessment, and referral to other specialties. The panel members reviewed a summary of all responses and reached a consensus. The result was presented as a clinical pathway. CONCLUSION: The panel concluded that our current awareness of dry skin and therefore prevention and effective treatment is limited; that identifying dry skin and its clinical issues requires tools such as clinical pathways, which may improve patient outcomes; and that additional research on dry skin etiology, prevention, and treatment is necessary.

Intraoperative frozen section analysis of urethral margin biopsies during radical prostatectomy.

OBJECTIVES: To evaluate the accuracy and potential clinical value of intraoperative frozen section analysis (FSA) on urethral margin (UM) tissue during radical prostatectomy. Positive surgical margins increase the risk of post-operative cancer recurrence. Positive surgical margins are frequently found at the apex. The utility of intraoperative FSA of the margins is controversial. METHODS: We reviewed a consecutive series of radical prostatectomy cases (n = 1669) performed at our institution, in which UMs were routinely evaluated by intraoperative FSA. RESULTS: The submitted UM tissue contained cancer glands in 111 cases (6.7%). On FSA, the pathologists detected cancer in 55 cases (3.3%), missed cancer in 38 (2.3%), and reported atypical glands in 18 (1.1%). FSA of the UMs had a sensitivity of 59.1%, specificity of 99.8%, and positive and negative predictive value of 94.8% and 97.6%, respectively. The low sensitivity resulted from a substantial false-negative rate (n = 38), which was largely attributed to limited sampling on FSA (n = 31). Of the 55 patients (3.3%) whose positive UMs were detected by FSA, 20 (1.2%) had cancer-free margins after tissue re-excision. A positive final UM was associated with greater biochemical recurrence (P = .0073). However, the few patients limited the statistical analysis of the benefit of margin conversion through tissue re-excision (P = .35). CONCLUSIONS: Although experienced pathologists can evaluate the UMs on FSA with good accuracy, FSA has a relatively low sensitivity. Our data have indicated a low yield and a questionable value of routine FSA during radical prostatectomy.

Acidic residues in the purine binding site govern the 6-oxopurine specificity of the Leishmania donovani xanthine phosphoribosyltransferase.

Leishmania possess distinct xanthine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase enzymes that mediate purine salvage, an obligatory nutritional function for these pathogenic parasites. The xanthine phosphoribosyltransferase preferentially uses xanthine as a substrate, while the hypoxanthine-guanine phosphoribosyltransferase phosphoribosylates only hypoxanthine and guanine. These related phosphoribosyltransferases were used as model system to investigate the molecular determinants regulating the 6-oxopurine specificity of these enzymes. Analysis of the purine binding domains showed two conserved acidic amino acids; glutamate residues in the xanthine phosphoribosyltransferase (E198 and E215) and aspartate residues in the hypoxanthine-guanine phosphoribosyltransferase (D168 and D185). Genetic and biochemical analysis established that the single E198D and E215D mutations increased the turnover rates of the xanthine phosphoribosyltransferase without altering purine nucleobase specificity. However, the E215Q and E198,215D mutations converted the Leishmania xanthine phosphoribosyltransferase into a broad-specificity enzyme capable of utilizing guanine, hypoxanthine, and xanthine as substrates. Similarly, the D168,185E double mutation transformed the Leishmania hypoxanthine-guanine phosphoribosyltransferase into a mutant enzyme capable phosphoribosylating only xanthine, albeit with a much lower catalytic efficiency. These studies established that these conserved acidic residues play an important role in governing the nucleobase selectivity of the Leishmania 6-oxopurine phosphoribosyltransferases.

Impact of surgeon selection on access placement and survival following preoperative mapping in the "Fistula First" era.

According to the "Fistula First Initiative" surgeon selection should be based on best outcomes, willingness, and ability to provide access services. This analysis presents arteriovenous access placement and outcomes in 75 patients when surgery was performed by one of two dedicated high-volume vascular access surgeons (community [surgeon I] and academic medical center [surgeon II]). Preoperative vascular mapping was performed in all the patients. Demographic characteristics were similar except that patients referred to surgeon I (n = 40) were older (52.7 +/- 16.2 years vs. 45.4 +/- 13.7 years; p = 0.04) and tended to have more previously failed accesses (50% vs. 29%; p = 0.06) and black race (65% vs. 43%; p = 0.055) including a history of previously failed accesses (50% for surgeon I and 29% for surgeon II; p = 0.06). Similarly, there was no significant difference in the size of forearm ([surgeon I: 2.0 +/- 1.0 mm], [surgeon II: 1.9 +/- 0.8 mm]; p = 0.45) or upper arm veins (cephalic vein: surgeon I = 3.2 +/- 1.4 mm, surgeon II = 2.9 +/- 1.2 mm, p = 0.34; basilic vein: surgeon I = 5.0 +/- 1.2 mm, surgeon II = 4.7 +/- 1.3 mm, p = 0.25). Fistulae placement occurred in 98% vs. 71% (p = 0.001) for surgeon I and II, respectively. Characteristics predictive of fistula placement over an arteriovenous graft were surgeon selection (odds ratio [OR] = 19.52; p = 0.01) and no history of diabetes (OR = 7.61; p = 0.016). Kaplan-Meier analysis revealed 6 and 12 months overall access survival rates of 82%, 58% and 82% and 47% for surgeon I and II, respectively (p = 0.007). This analysis demonstrates that surgeon selection can have a significant impact on the rate of fistula placement and its overall survival despite similar findings on preoperative vascular mapping.

Accuracy of physical examination in the detection of arteriovenous graft stenosis.

Physical examination has recently been demonstrated to detect vascular access stenosis in patients with arteriovenous fistulae. However, its accuracy in the identification of stenoses when compared with the gold standard (angiography) in patients with arteriovenous grafts has not been studied in a systematic fashion. We conducted a prospective study to examine the accuracy of physical examination in the detection of stenotic lesions when compared with angiography. Forty-three consecutive cases referred for an arteriovenous graft dysfunction were included in this analysis. Preprocedure physical examination was performed. The findings of the examination and diagnosis were recorded and secured in a sealed envelope. Angiography from the feeding artery to the right atrium was performed. The images were reviewed by an independent interventionalist with expertise in endovascular dialysis access procedures and the diagnosis was rendered. The reviewer was blinded to the physical examination. Cohen's Kappa was used as a measurement of the level of agreement beyond chance between the diagnosis made by physical examination and angiography. There was a strong agreement between the physical examination and the angiography in the diagnosis of vein-graft anastomotic stenosis (kappa = 0.52). The sensitivity and specificity for this lesion was 57% and 89%, respectively. There was a moderate agreement beyond chance regarding the diagnosis of intragraft (kappa = 0.43) and inflow stenoses (kappa = 0.40). The sensitivity and specificity for the intragraft and inflow stenosis was 100%, 73% and 33%, 73%; respectively. The findings of this study demonstrate that physical examination can assist in the detection and localization of stenoses in arteriovenous grafts.

Accuracy of physical examination in the detection of arteriovenous fistula stenosis.

BACKGROUND AND OBJECTIVES: Physical examination has been highlighted to detect vascular access stenosis; however, its accuracy in the identification of stenoses when compared with the gold standard (angiography) has not been validated in a systematic manner. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective study was conducted of 142 consecutive patients who were referred for an arteriovenous fistula dysfunction to examine the accuracy of physical examination in the detection of stenotic lesions when compared with angiography. The findings of a preprocedure physical examination and diagnosis were recorded and secured in a sealed envelope. Angiography from the feeding artery to the right atrium was then performed. The images were reviewed by an independent interventionalist who had expertise in endovascular dialysis access procedures and was blinded to the physical examination, and the diagnosis was rendered. Cohen's kappa was used as a measurement of the level of agreement beyond chance between the diagnosis made by physical examination and angiography. RESULTS: There was strong agreement between physical examination and angiography in the diagnosis of outflow (agreement 89.4%, kappa = 0.78) and inflow stenosis (agreement 79.6%, kappa = 0.55). The sensitivity and specificity for the outflow and inflow stenosis were 92 and 86% and 85 and 71%, respectively. There was strong agreement beyond chance regarding the diagnosis of coexisting inflow-outflow lesions between physical examination and angiography (agreement 79%, kappa = 0.54). CONCLUSIONS: The findings of this study demonstrate that physical examination can accurately detect and localize stenoses in a great majority of arteriovenous fistulas.

Hypertension treatment guidelines: practical implications.

The focus of blood pressure (BP) lowering is to prevent or reduce the risk for cardiovascular and renal events. This rationale forms the basis for the recent guideline statements issued by the Seventh Joint National Committee, the American Diabetes Association, the European Society of Hypertension, and the Kidney Disease Outcomes Quality Initiative. The goal BP in the majority of hypertensive patients should be less than 140/90 mm Hg, with a lower goal of less than 130/80 mm Hg in patients with diabetes or kidney disease. Meta-analyses of clinical trials with renal end points make it clear that the presence of 1 gram or more of proteinuria mandates a BP approaching 115 mm Hg to slow the progression of advanced nephropathy adequately. Compelling indications also exist for the use of certain antihypertensive agents in the setting of kidney dysfunction, diabetes, heart failure, and coronary artery disease. Initiation with 2 antihypertensive agents should be considered strongly for patients with a BP of more than 20 mm Hg greater than the systolic BP goal. This means that those with a goal BP of less than 130 mm Hg should be started on 2 antihypertensive medications with complementary actions when the systolic BP is 150 mm Hg or greater. In patients with kidney disease, reaching the BP goal requires multiple agents that should include an appropriate diuretic and an agent that blocks the renin-angiotensin-aldosterone system to slow the progression of kidney disease.

Antihypertensive, antiproteinuric therapy and myocardial infarction and stroke prevention.

Proteinuria is a graded marker for kidney damage, as well as the risk for future cardiovascular events. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) reduce urinary protein excretion and slow progression of renal impairment, independent of blood pressure lowering. Both the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction in Endpoints in NIDDM with the Angiotensin Antagonist Losartan (RENAAL) study were large, randomized, prospective studies in type 2 diabetic patients with proteinuria. There was no reduction in the incidence of myocardial infarction or stroke with the ARBs compared to placebo in either trial. A broader overview of clinical trials comparing ACEIs and ARBs with other antihypertensive drugs fails to show any substantive blood pressure-independent effects on stroke or myocardial infarction with these classes of drugs. Therefore, for cardiovascular end points (as opposed to renal end points), it may be more important that the blood pressure is reduced, rather than how the process is started.