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N -Nitrosamines are a class of indirect acting mutagens, as their metabolic degradation leads to the formation of the DNA-alkylating diazonium ion. Following up on the in-silico identification of thousands of nitrosamines that can potentially be derived from small molecule drugs and their known impurities described in a previous publication, we have now re-analyzed this dataset to apply EMA's Carcinogenic Potency Categorization Approach (CPCA) introduced with the 16th revision of their Q&A document for Marketing Authorization Holders. We find that the majority of potential nitrosamines from secondary amine precursors belongs to potency categories 4 and 5, corresponding to an acceptable daily intake of 1500 ng, whereas nitrosamines from tertiary amine precursors distribute more evenly among all categories, resulting in a substantial number of structures that are assigned the more challenging acceptable intakes of 18 ng/day and 100 ng/day for potency categories 1 and 2, respectively. However, the nitrosative dealkylation pathway for tertiary amine is generally far slower than the direct nitrosation on secondary amines, with a direct nitrosation mechanism suspected only for structures featuring electron-rich (hetero)aromatic substituents. This allows for greater focus towards those structures that require further review, and we demonstrate that their number is not substantial. In addition, we reflect on the nitrosamine risk posed by secondary amine API impurities and demonstrate that based on the ICH Q3A/B identification threshold unknown impurities may exist that could be transformed to relevant amounts of NA. We also demonstrate that the analytical sensitivity required for the quantification of high potency nitrosamines can be problematic especially for high dose APIs. In summary, the regulatory framework rolled out with the latest Q&A document represents a substantial improvement compared with the previous situation, but further refinement through interaction between manufacturers, regulators, not-for-profit and academic institutions will be required to ensure patient access to vital medicines without compromising safety. [Display omitted] [ABSTRACT FROM AUTHOR]

This article reports the outcome of an in silico analysis of more than 12,000 small molecule drugs and drug impurities, identifying the nitrosatable structures, assessing their potential to form nitrosamines under relevant conditions and the challenges to determine compound-specific AIs based on data available or read-across approaches for these nitrosamines and their acceptance by health authorities. Our data indicate that the presence of nitrosamines in pharmaceuticals is likely more prevalent than originally expected. In total, 40.4 % of the analyzed APIs and 29.6 % of the API impurities are potential nitrosamine precursors. Most structures identified through our workflow could form complex API-related nitrosamines, so-called nitrosamine drug substance related impurities (NDSRIs), although we also found structures that could release the well-known small and potent nitrosamines NDMA, NDEA, and others. Due to common structural motifs including secondary or tertiary amine moieties, whole essential drug classes such as beta blockers and ACE inhibitors are at risk. To avoid the risk of drug shortages or even the complete loss of therapeutic options, it will be essential that the well-established ICH M7 principles remain applicable for nitrosamines and that that the industry and regulatory authorities keep an open communication not only about the science but also to make sure there is a good balance between risk and benefit to patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Utility of the pyridazine motif is growing in popularity as pharmaceutical and agrochemical agents. The detection and structural characterisation of such materials is therefore imperative for the successful development of new products. Signal amplification by reversible exchange (SABRE) offers a route to dramatically improve the sensitivity of magnetic resonance methods, and we apply it here to the rapid and cost‐effective hyperpolarisation of substituted pyridazines. The 33 substrates investigated cover a range of steric and electronic properties and their capacity to perform highly effective SABRE is assessed. We find the method to be tolerant to a broad range of electron donating and withdrawing groups; however, good sensitivity is evident when steric bulk is added to the 3‐ and 6‐positions of the pyridazine ring. We optimise the method by reference to a disubstituted ester that yields signal gains of >9000‐fold at 9.4 T (>28% spin polarisation). [ABSTRACT FROM AUTHOR]

Key message: Moisture content during nixtamalization can be accurately predicted from NIR spectroscopy when coupled with a support vector machine (SVM) model, is strongly modulated by the environment, and has a complex genetic architecture. Lack of high-throughput phenotyping systems for determining moisture content during the maize nixtamalization cooking process has led to difficulty in breeding for this trait. This study provides a high-throughput, quantitative measure of kernel moisture content during nixtamalization based on NIR scanning of uncooked maize kernels. Machine learning was utilized to develop models based on the combination of NIR spectra and moisture content determined from a scaled-down benchtop cook method. A linear support vector machine (SVM) model with a Spearman's rank correlation coefficient of 0.852 between wet laboratory and predicted values was developed from 100 diverse temperate genotypes grown in replicate across two environments. This model was applied to NIR spectra data from 501 diverse temperate genotypes grown in replicate in five environments. Analysis of variance revealed environment explained the highest percent of the variation (51.5%), followed by genotype (15.6%) and genotype-by-environment interaction (11.2%). A genome-wide association study identified 26 significant loci across five environments that explained between 5.04% and 16.01% (average = 10.41%). However, genome-wide markers explained 10.54% to 45.99% (average = 31.68%) of the variation, indicating the genetic architecture of this trait is likely complex and controlled by many loci of small effect. This study provides a high-throughput method to evaluate moisture content during nixtamalization that is feasible at the scale of a breeding program and provides important information about the factors contributing to variation of this trait for breeders and food companies to make future strategies to improve this important processing trait. [ABSTRACT FROM AUTHOR]

Anodized alumina membranes (AAMs) have proven effective at making vertically-oriented and well-ordered metal nanowire arrays, which are useful in plasmonics and electrochemistry. Here, we produced Al nanowires via directed AAM pore nucleation: a patterned oxide mask on a flat Al surface directed where pores did and did not form, the pores acting to oxidize Al around the sites without pores. This left Al nanowires embedded in the AAM, and produced freestanding Al nanowires after etching the AAM. The nanowire tops had two distinct contours, smooth bowls and flat rough surfaces—suggesting that nanowires with bowl tops result from slow pore development relative to pattern-nucleated pores, not pore blockage as prior literature suggests. The observed low porosity of ∼2%, as opposed to the more typical 10%, suggests pore nucleation in the electrolyte employed may need greater local variations in electric field or pH, possibly explaining the electrolyte's peculiar ability to make Al nanowires. Finally, a soft nano-imprint lithography process was developed here to pattern the mask without damaging the stamp, avoiding a stamp degradation problem in previous work that utilized hard nano-imprint lithography. [ABSTRACT FROM AUTHOR]

By introducing a range of 2H labels into pyridine and the para‐substituted agents, methyl isonicotinate and isonicotinamide, we significantly improve their NMR detectability in conjunction with the signal amplification by reversible exchange process. We describe how the rates of T1 relaxation for the remaining 1H nuclei are increased and show how this leads to a concomitant increase in the level of 1H and 13C hyperpolarization that can ultimately be detected. [ABSTRACT FROM AUTHOR]

Hyperpolarization turns typically weak NMR and MRI responses into strong signals so that ordinarily impractical measurements become possible. The potential to revolutionize analytical NMR and clinical diagnosis through this approach reflect this area's most compelling outcomes. Methods to optimize the low-cost parahydrogen-based approach signal amplification by reversible exchange with studies on a series of biologically relevant nicotinamides and methyl nicotinates are detailed. These procedures involve specific ²H labeling in both the agent and catalyst and achieve polarization lifetimes of ca. 2 min with 50% polarization in the case of methyl-4,6-d2-nicotinate. Because a 1.5-T hospital scanner has an effective ¹H polarization level of just 0.0005% this strategy should result in compressed detection times for chemically discerning measurements that probe disease. To demonstrate this technique's generality, we exemplify further studies on a range of pyridazine, pyrimidine, pyrazine, and isonicotinamide analogs that feature as building blocks in biochemistry and many disease-treating drugs. [ABSTRACT FROM AUTHOR]

The first total synthesis of phacelocarpus 2-pyrone A is reported. The original natural compound was tentatively assigned (by NMR spectroscopy) as containing two cis-alkenes and a trans-vinyl ether connected to a 2-pyrone ring motif. Our computational predictions indicated that a cis-vinyl ether motif was equally feasible. Attempts to prepare the trans-vinyl ether were met with no success. The all cis-target compound was synthesised in nine steps, employing key regio- and stereoselective reactions including AuI-catalysed vinyl etherification, Wittig alkenylation and end-game Stille macrocyclisation. Analysis of the NMR data enabled identification and confirmation of the correct structure of phacelocarpus 2-pyrone A, containing a cis-vinyl ether. Our studies pave the way for future development of methodologies to these structurally distinct pyrone skipped-polyenyne natural products. [ABSTRACT FROM AUTHOR]

Consumption of corn-based foods is increasing in the United States and globally. Little is known about changes in kernel compositional profiles, including levels of acrylamide precursors (e.g. asparagine and reducing sugars), when corn kernels are cooked in a process called nixtamalization. The objectives of this study were to investigate the compositional variation of raw starting materials, general compositional changes during nixtamalization, and genotype specific patterns of change for acrylamide precursors during this process. A panel of 120 genotypes were subject to a small-scale bench top cooking protocol to investigate compositional changes that occur during cooking and steeping. Substantial variation was observed in the raw starting material for all compositional traits that were measured including asparagine, fructose, glucose, crude protein, and starch. During nixtamalization a decrease in asparagine, glucose, and fructose mean and variation was observed, while crude protein and starch remained relatively stable. Analysis of the genotype-by-subsample interactions (after cooking and after steeping) revealed variation in compositional changes in response to cooking among the genotypes. These findings reveal the dynamics of compositional traits during nixtamalization of corn kernels. This information can be used by plant breeders and food processors to more effectively make acrylamide mitigation strategies. • There was significant variation in the raw material for acrylamide precursors. • There was variability in chemical changes in response to the cooking process. • Nixtamalization decreased overall mean and variance for acrylamide precursors. [ABSTRACT FROM AUTHOR]

Traditional 31P NMR orMRI measurements suffer fromlow sensitivity relative to 1H detection and consequentlyrequire longer scan times. We show here that hyperpolarization of 31P nuclei through reversible interactions with parahydrogen can deliver substantial signal enhancements in a range ofregioisomeric phosphonate esters containing a heteroaromatic motifwhich were synthesized in order to identify the optimum molecularscaffold for polarization transfer. A 3588-fold 31P signalenhancement (2.34% polarization) was returned for a partially deuteratedpyridyl substituted phosphonate ester. This hyperpolarization levelis sufficient to allow single scan 31P MR images of a phantomto be recorded at a 9.4 T observation field in seconds that have signal-to-noiseratios of up to 94.4 when the analyte concentration is 10 mM. In contrast,a 12 h 2048 scan measurement under standard conditions yields a signal-to-noiseratio of just 11.4. 31P-hyperpolarized images are alsoreported from a 7 T preclinical scanner. [ABSTRACT FROM AUTHOR]

Recently, various light trapping schemes based on inclusions of dielectric or metallic nanoparticles or nanopatterns on top of, below, or embedded within a photovoltaic (PV) absorber have been proposed to enhance the efficiency of solar cells. We demonstrate here that embedded metal nanopatterns (EMN) within the absorber layers of thin film solar cells can serve as a general scheme for broadband light absorption enhancement. The EMN scheme is compatible with a wide variety of non-crystalline solar cells, including amorphous, polycrystalline, organic, polymeric, and dye-sensitized solar cells. Simulations on the same EMN in various PV media show consistent absorption enhancement. An impedance matching model is used to explain the robustness of the effect, wherein the EMN brings the impedance of the thin-film solar cell closer to that of free space in a broadband manner, resulting in exceptional absorption enhancement in the near band gap regime. Experimental verifications are provided by Ag connecting network nanopatterns fabricated by nanosphere lithography embedded in an amorphous silicon layer, resulting in a broadband absorbance enhancement, especially in the near band gap region, in good agreement with our predictions. Connecting Ag networks with hexagonal close-packed holes are fabricated by nanosphere lithography, and then embedded into an amorphous silicon layer. For increasing embedding depth d from 5.3 to 18.4 nm, the absorbance of the structure increases, especially at the near band gap region. [ABSTRACT FROM AUTHOR]

The use of aluminum (Al) as a plasmonic building block has drawn increasing attention of late, due to its natural abundance, and extended tunability into the ultraviolet range. However, a controllable way to grow Al nanowires (NWs) in a bottom-up manner has not been reported. Here a facile, stress-induced growth process for Al nanowires, influenced by the concentration of applied hydrofluoric acid, is reported. Physical characterizations show the nanowires to be polycrystalline fcc Al with ultrasmooth surfaces, with many possible cross-section geometries, making them potential candidates for Al plasmonic investigations and applications. Dark-field optical analysis of a crescent-shaped Al NW demonstrates its plasmonic nature. These results may stimulate new interest in the fabrication of unconventional, nearly one dimensional Al nanostructures. [ABSTRACT FROM AUTHOR]

We observe asymmetric color filtering under unpolarized incidence in a structured metallic (Ag) film, where the center of an optically thick circular Ag disk surrounded by a step gap appears dark when observed from one side, and bright from the other. The latter situation corresponds to abnormally high optical transmission through the optically thick film.Weexplain this by a three-step process: coupling of photons to surface plasmon polaritons (SPPs), wave interference of SPPs forming resonant cavity modes, and out-coupling from SPPs to photons. Full wave electromagnetic simulations based on the finite element method support our findings. These results may have potential applications in areas such as optical color filtering and biosensing via dielectric detection within the step gap plasmonic cavity. [ABSTRACT FROM AUTHOR]

Gradient‐index meta‐surfaces have been shown to have the ability to manipulate wavefronts at will in a reflectionless manner in the GHz range, including the extreme example of converting freely propagating waves into surface waves with high efficiency. Upon approaching the optical regime, the gradient‐index concept encounters difficulties due to fabrication limitations. Here, it is theoretically and experimentally demonstrated that asymmetric, periodic, two‐element metal–insulator–metal structures can serve as reflectionless directional converters between freely propagating visible photons and surface plasmon polaritons (SPPs). Coupling between propagating modes caused by the broken symmetry and localized modes generated by individual elements is shown to be the mechanism of this high‐efficiency process, yielding an observed Rabi splitting of ∼135 meV. Direct experimental evidence is obtained for reflectionless (<8% measured reflectance) directional SPP coupling in the visible range, with directionality approaching 100%. These results are meaningful for varied applications in integrated nanoplasmonics, plasmonic logic, and plasmonic light harvesting. [ABSTRACT FROM AUTHOR]

Signal Amplification by Reversible Exchange (SABRE) is an inexpensive and simple hyperpolarization technique that is capable of boosting nuclear magnetic resonance sensitivity by several orders of magnitude. It utilizes the reversible binding of para-hydrogen, as hydride ligands, and a substrate of interest to a metal catalyst to allow for polarization transfer from para-hydrogen into substrate nuclear spins. While the resulting nuclear spin populations can be dramatically larger than those normally created, their lifetime sets a strict upper limit on the experimental timeframe. Consequently, short nuclear spin lifetimes are a challenge for hyperpolarized metabolic imaging. In this report, we demonstrate how both hyperpolarization and long nuclear spin lifetime can be simultaneously achieved in nitrogen-15 containing derivatives of pyridazine and phthalazine by SABRE. These substrates were chosen to reflect two distinct classes of 15N2-coupled species that differ according to their chemical symmetry and thereby achieve different nuclear spin lifetimes. The pyridazine derivative proves to exhibit a signal lifetime of ∼2.5 min and can be produced with a signal enhancement of ∼2700. In contrast, while the phthalazine derivative yields a superior 15 000-fold 15N signal enhancement at 11.7 T, it has a much shorter signal lifetime. [ABSTRACT FROM AUTHOR]

We present the observation and systematic study of anovel opticalphenomenon, a “plasmonic halo”, wherein surface plasmonsoptically excited on circular silver microcavities form confined drumheadmodes that, under resonant conditions, emanate colorful far-fieldradiation from their perimeter boundaries. We demonstrate both experimentallyand theoretically that such circular microcavities integrated withperimeter step gaps can generate surface plasmon cavity modes whichmodulate optical transmission/emission through/from the device, yieldingthe plasmonic halo effect. Via the tuning of geometric and/or materialparameters, optical properties of this device can be manipulated inthe visible range, leading to potential applications in biomedicalplasmonics and discrete optical filtering, among others. [ABSTRACT FROM AUTHOR]

Simulations of metal nanopatterns embedded in a thin photovoltaic (PV) absorber show significantly enhanced absorbance within the semiconductor, with a more than 300% increase for λ = 800 nm. Integrating with AM1.5 solar irradiation, this yields a 70% increase in simulated short circuit current density in a 60 nm amorphous silicon film. Embedding such metal patterns inside an absorber maximally utilizes enhanced electric fields that result from intense, spatially organized, near-field scattering in the vicinity of the pattern. Appropriately configured (i.e., with a thin insulating coating), this optical metamedium architecture may be useful for increasing PV efficiency in thin film solar cells, including offering prospects for realistic ultrathin hot electron cells. Simulated time averaged power loss density within a-Si in the vicinity of a silver cross EMN, for unpolarized 700 nm light. [ABSTRACT FROM AUTHOR]

A new synthetic methodology for the catalytic C–H functionalisation of 2-pyrones is described which proceeds regioselectively at the C3 position, mirroring the observed regioselectivity in 6π-electrocyclisation/oxidative aromatisation reactions of related compounds. Insight into the reaction mechanism is provided, with support for a neutral palladium(ii) pathway. Cationic palladium(ii) complexes possessing 2-pyrones are unstable and readily undergo PdII→P transfer at ambient temperature resulting in phosphonium salt formation (and Pd0Lnspecies). [ABSTRACT FROM AUTHOR]

We describe a very simple method for making a low-cost wide-band position-sensitive photodetector (PSD) and preamplifier circuit. The detector is most suitable for experiments where a laser is used to measure the deflection (linear or angular) of some part of the experimental apparatus. The response of the photodetector is exponential for static beam position changes and linear for oscillating position. The static deflection exponential behavior can be linearized with a logarithmic preamplifier circuit. The detector can also be used as a low-cost laser beam intensity monitor with only a few percent beam loss and approximately 100 dB of dynamic range. We have fabricated PSDs and beam-power monitors capable of operating at wavelengths from 0.2 to 1 μm and by a suitable change of components this range should be extendable from 0.1 up to 22 μm. [ABSTRACT FROM AUTHOR]

Infection with hepatitis A virus (HAV) causes a highly contagious illness that can lead to serious morbidity and occasional mortality. Although the overall incidence of HAV has been declining since the introduction of the HAV vaccine, there have been an increasing number of outbreaks within the United States and elsewhere between 2016 and 2017. These outbreaks have had farreaching consequences, with a large number of patients requirin g hospitalization and several deaths. Accordingly, HAV is proving to present a renewed public health challenge. Through use of the "Identify-Isolate-Inform" tool as adapted for HAV, emergency physicians can become more familiar with the identification and management of patients presenting to the emergency department (ED) with exposure, infection, or risk of contractin g disease. While it can be asymptomatic, HAV typically presents with a prodrome of fever, nausea/vomiting and abdominal pain followed by jaundice. Healthcare providers should maintain strict standard precautions for all patients suspected of having HAV infection as well as contact precautions in special cases. Hand hygiene with soap and warm water should be emphasized and affected patients should be counseled to avoid food preparation and close contact with vulnerable populations. Additionally, ED providers should offer post-exposure prophylaxis to exposed contacts and encourage vaccination as well as other preventive measures for at-risk individuals. ED personnel should inform local public health departments of any suspected case. [ABSTRACT FROM AUTHOR]

Assesses the stability of negative pressures within the xylem in plants by experimentally imposing xylem tension by centrifugal force. Role of xylem in transporting water within the plant system; Estimation of pressures with a pressure chamber; Balancing pressure measurements; Capability of the xylem to sustain large negative pressures.

First isolated in 1947 from a monkey in the Zika forest in Uganda, and from mosquitoes in the same forest the following year, Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. More than one million people have been infected since the appearance of the virus in Brazil in 2015. Approximately 80% of infected patients are asymptomatic. An association with microcephaly and other birth defects as well as Guillain-Barre Syndrome has led to a World Health Organization declaration of Zika virus as a Public Health Emergency of International Concern in February 2016. Zika virus is a vector-borne disease transmitted primarily by the Aedes aegypti mosquito. Male to female sexual transmission has been reported and there is potential for transmission via blood transfusions. After an incubation period of 2-7 days, symptomatic patients develop rapid onset fever, maculopapular rash, arthralgia, and conjunctivitis, often associated with headache and myalgias. Emergency department (ED) personnel must be prepared to address concerns from patients presenting with symptoms consistent with acute Zika virus infection, especially those who are pregnant or planning travel to Zika-endemic regions, as well as those women planning to become pregnant and their partners. The identify-isolate-inform (3I) tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED, and later adjusted for measles and Middle East Respiratory Syndrome, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for initial detection and management of patients under investigation for Zika virus. Following an assessment of epidemiologic risk, including travel to countries with mosquitoes that transmit Zika virus, patients are further investigated if clinically indicated. If after a rapid evaluation, Zika or other arthropod-borne diseases are the only concern, isolation (contact, droplet, airborne) is unnecessary. Zika is a reportable disease and thus appropriate health authorities must be notified. The modified 3I tool will facilitate rapid analysis and triggering of appropriate actions for patients presenting to the ED at risk for Zika. [ABSTRACT FROM AUTHOR]

The evolution of micro/nanoelectronics technology, including the shrinking of devices and integrated circuit components, has included the miniaturization of linear and coaxial structures to micro/nanoscale dimensions. This reduction in the size of coaxial structures may offer advantages to existing technologies and benefit the exploration and development of new technologies. The reduction in the size of coaxial structures has been realized with various permutations between metals, semiconductors and dielectrics for the core, shield, and annulus. This review will focus on fabrication schemes of arrays of metal -nonmetal - metal nanocoax structures using non-template and template methods, followed by possible applications. The performance and scientific advantages associated with nanocoax-based optical devices including waveguides, negative refractive index materials, light emitting diodes, and photovoltaics are presented. In addition, benefits and challenges that accrue from the application of novel nanocoax structures in energy storage, electronic and sensing devices are summarized. [ABSTRACT FROM AUTHOR]

A 21-year-old woman was admitted to the emergency department (ED) with severe sepsis. Both the mechanism of infection and organisms discovered were unusual. [ABSTRACT FROM AUTHOR]

Pertussis, commonly referred to as "whooping cough," is a highly contagious acute respiratory infection that has exhibited cyclical outbreaks throughout the last century. Although vaccines have provided some immunity, many populations, including infants and pregnant women, remain at risk for serious illness. Through the use of the novel "Identify, Isolate, Inform" (3I) tool, emergency department (ED) providers can readily recognize key symptoms of the disease and risk factors for exposure, thus curbing its transmission through early initiation of antimicrobial therapy and post-exposure prophylaxis. The three classic stages of pertussis include an initial catarrhal stage, characterized by nonspecific upper respiratory infection symptoms, which may advance to the paroxysmal stage, revealing the distinctive "whooping cough." This cough can persist for weeks to months leading into the convalescent stage. Household contacts of patients with suspected pertussis or other asymptomatic, high-risk populations (infants, pregnant women in their third trimester, and childcare workers) may benefit from post-exposure prophylactic therapy. The Pertussis 3I tool can also alert healthcare professionals to the proper respiratory droplet precautions during contact with a symptomatic patient, as well as isolation practices until antimicrobial treatment is in progress. ED personnel should then inform local public health departments of any suspected cases. All of these actions will ultimately aid public health in controlling the incidence of pertussis cases, thus ensuring the protection of the general public from this re-emerging respiratory illness. [ABSTRACT FROM AUTHOR]

A scalable and a fully solution‐based method is developed to produce environmentally stable Ag micro/nanowire networks for transparent conductors. By applying a self‐cracking, water‐soluble acrylate copolymer film as a photoresist mask, the need for formal photomask fabrication and costly vacuum and lithographic facilities is obviated. Also, an increase in adhesion and a decrease in roughness of the metal networks is demonstrated by depositing metal into the regions created by the glass etch step. As a result, the networks can potentially be inexpensively scaled to large areas, as well as be flexible after removal from the substrate. They also exhibit record values of figures of merit that have been employed in the literature, offering a possibly excellent replacement for ITO. [ABSTRACT FROM AUTHOR]

Mumps is a highly contagious viral infection that became rare in most industrialized countries following the introduction of measles-mumps-rubella (MMR) vaccine in 1967. The disease, however, has been re-emerging with several outbreaks over the past decade. Many clinicians have never seen a case of mumps. To assist frontline healthcare providers with detecting potential cases and initiating critical actions, investigators modified the "Identify-Isolate-Inform" tool for mumps infection. The tool is applicable to regions with rare incidences or local outbreaks, especially seen in college students, as well as globally in areas where vaccination is less common. Mumps begins with a prodrome of low-grade fever, myalgias and malaise/anorexia, followed by development of nonsuppurative parotitis, which is the pathognomonic finding associated with acute mumps infection. Orchitis and meningitis are the two most common serious complications, with hearing loss and infertility occurring rarely. Providers should consider mumps in patients with exposure to a known case or international travel to endemic regions who present with consistent signs and symptoms. If mumps is suspected, healthcare providers must immediately implement standard and droplet precautions and notify the local health department and hospital infection control personnel. [ABSTRACT FROM AUTHOR]

Sensitive, real-time detection of biomarkers is of critical importance for rapid and accurate diagnosis of disease for point of care (POC) technologies. Current methods do not allow for POC applications due to several limitations, including sophisticated instrumentation, high reagent consumption, limited multiplexing capability, and cost. Here, we report a nanocoaxial-based electrochemical sensor for the detection of bacterial toxins using an electrochemical enzyme-linked immunosorbent assay (ELISA) and differential pulse voltammetry (DPV) or square wave voltametry (SWV). The device architecture is composed of vertically-oriented, nanoscale coaxial electrodes in array format (~10 6 coaxes per square millimeter). The coax cores and outer shields serve as integrated working and counter electrodes, respectively, exhibiting a nanoscale separation gap corresponding to ~100 nm. Proof-of-concept was demonstrated for the detection of cholera toxin (CT). The linear dynamic range of detection was 10 ng/ml–1 µg/ml, and the limit of detection (LOD) was found to be 2 ng/ml. This level of sensitivity is comparable to the standard optical ELISA used widely in clinical applications, which exhibited a linear dynamic range of 10 ng/ml–1 µg/ml and a LOD of 1 ng/ml. In addition to matching the detection profile of the standard ELISA, the nanocoaxial array provides a simple electrochemical readout and a miniaturized platform with multiplexing capabilities for the simultaneous detection of multiple biomarkers, giving the nanocoax a desirable advantage over the standard method towards POC applications. [ABSTRACT FROM AUTHOR]

Signal amplification by reversible exchange (SABRE) of a substrate and parahydrogen at a catalytic center promises to overcome the inherent insensitivity of magnetic resonance. In order to apply the new approach to biomedical applications, there is a need to develop experimental equipment, in situ quantification methods, and a biocompatible solvent. We present results detailing a low-field SABRE polarizer which provides well-controlled experimental conditions, defined spins manipulations, and which allows in situ detection of thermally polarized and hyperpolarized samples. We introduce a method for absolute quantification of hyperpolarization yield in situ by means of a thermally polarized reference. A maximum signal-to-noise ratio of ~103 for 148 μmol of substance, a signal enhancement of 106 with respect to polarization transfer field of SABRE, or an absolute 1H-polarization level of ≈10–2 is achieved. In an important step toward biomedical application, we demonstrate 1H in situ NMR as well as 1H and 13C high-field MRI using hyperpolarized pyridine (d3) and 13C nicotinamide in pure and 11% ethanol in aqueous solution. Further increase of hyperpolarization yield, implications of in situ detection, and in vivo application are discussed. [ABSTRACT FROM AUTHOR]

We have used a facile polymer imprint process to fabricate a three-dimensional electrochemical nanosensor, the sensitivity of which is two decades higher than that of planar controls. The device is composed of an array of vertically oriented nanoscale coaxial electrodes, with the coax cores and shields serving as integrated working and counter electrodes, respectively, each with a nanoscale separation gap (coax annulus width). Arrays of ~106 devices per square millimeter were prepared with different gaps, with smaller gaps yielding higher sensitivity. A coax-based sensor with a 100 nm gap was found to have sensitivity 90 times greater than that of a planar sensor control, which had conventional millimeter-scale electrode gap spacing. We suggest that this enhancement is due to the combination of rapid diffusion of molecules between the closely spaced electrodes and the large number of nanoscale electrochemical cells operating in parallel, both of which enhance current per unit surface area compared to planar or other nanostructured devices. [ABSTRACT FROM AUTHOR]

Pd02(dba)3 (dba = E,E-dibenzylidene acetone) is the most widely used Pd0 source in Pd-mediated transformations. Pd02(dba-Z)3 (Z = dba aryl substituents) complexes exhibit remarkable and differential catalytic performance in an eclectic array of cross-coupling reactions. The precise structure of these types of complexes has been confounding, since early studies in 1970s to the present day. In this study the solution and solid-state structures of Pd02(dba)3 and Pd02(dba-Z)3 have been determined. Isotopic labeling (²H and `3C) has allowed the solution structures of the freely exchanging major and minor isomers of Pd02(dba)3 to be determined at high field (700 MHz). DFT calculations support the experimentally determined major and minor isomeric structures, which show that the major isomer of Pd02(dba)3 possesses bridging dba ligands found exclusively in a s-cis,s-trans conformation. For the minor isomer one of the dba ligands is found exclusively in a s-trans,s-trans conformation. Single crystal X-ray diffraction analysis of Pd02(dba)3·CHC13 (high-quality data) shows that all three dba ligands are found over two positions. NMR spectroscopic analysis of Pd02(dba-Z)3 reveals that the aryl substituent has a profound effect on the rate of Pd-olefln exchange and the global stability of the complexes in solution. Complexes containing the aryl substituents, 4-CF3, 4-F, 4-t-Bu, 4-hexoxy, 4-OMe, exhibit well-resolved ¹H NMR spectra at 298 K, whereas those containing 3,5-OMe and 3,4,5-OMe exhibit broad spectra. The solid-state structures of three Pd02(dba-Z)3 complexes (4-F, 4-OMe, 3,5-OMe) have been determined by single crystal X-ray diffraction methods, which have been compared with Goodson's X-ray structure of Pd02(dba-4-OH)3. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of abnormal karyotype results in women undergoing chorionic villus sampling (CVS) for abnormal first trimester screening compared to CVS for historical indications (advanced maternal age (AMA) or prior aneuploidy). Methods: Retrospective cohort of all patients undergoing CVS at Oregon Health & Science University from January 2006 to June 2010. Patients were separated based on CVS indication: (1) positive ultrasound (U/S) or serum screening; or (2) AMA or prior aneuploidy with normal or no screening. Prevalence of abnormal karyotype results were compared between groups. Results: Fetal karyotyping was successful in 500 of 506 CVS procedures performed. 203 CVS were performed for positive screening with 69 abnormal karyotypes (34.0%). 264 CVS were performed for historical indications with 11 abnormal karyotypes (4.2%). This difference was statistically significant (χ2 71.9, p < 0.001; OR 11.8 [95% CI 5.8, 24.6]). There were two age-related aneuplodies in AMA women without positive screening. 42 out of 44 AMA women diagnosed with aneuploidy (95.5%) had abnormal U/S and/or serum screening (35 U/S, 4 serum, 3 U/S and serum). Conclusions: Combined ultrasound and serum screening should be recommended to all women, including AMA women, prior to undergoing invasive testing to improve risk-based counseling and minimize morbidity. [ABSTRACT FROM AUTHOR]

Context. Rising aminotransferases (ATs) [either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are one of the first signs of hepatotoxicity following acetaminophen (APAP)] overdose (OD). However, the timing and speed of such rises are not well characterized, hampering early risk prediction. Objective. To describe the kinetics of AT release in acute APAP OD patients who develop hepatotoxicity despite treatment. Methods. A descriptive study of acute APAP OD patients with peak AT > 1,000 IU/L taken from the derivation subset of the Canadian Acetaminophen Overdose Study (CAOS), a large, multicenter retrospective cohort of patients hospitalized for APAP poisoning. Results. Of 2,488 hospital admissions for acute APAP OD, 94 met inclusion criteria. Treatment with acetylcysteine, mostly intravenously, was begun in all cases within 24 h of ingestion. The initial AT concentration was already elevated in most patients at presentation [median 211 (IQR 77-511) IU/L obtained at 15.3 (12.1-19.2) h postingestion], and exceeded 100 IU/L in almost all patients within 24 h of ingestion. Serum AT concentrations rose rapidly [doubling time 9.5 h (95% CI: 8.7-10.4 h)], especially in patients who developed AT > 1,000 IU/L within 48 h of ingestion. Coagulopathy was worse in these patients and in those with an AT > 250 IU/L during the first 12 h of treatment with acetylcysteine. Discussion and conclusions. An abnormal and rapidly doubling AT at presentation is more typical in severely poisoned patients, as judged by the effects on clotting. These data suggest that risk prediction instruments may be improved by incorporating both the serum AT concentration at initiation of antidotal therapy and its rate of change. Further studies using such an approach are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Previous literature on meningitis reports that cerebrospinal fluid (CSF) culture contaminants are threefold more common than true pathogens. Clinical follow-up of patients with CSF contaminants is costly, time-consuming, and potentially unnecessary. In this study, we hypothesized that, in immunocompetent Emergency Department (ED) patients with normal CSF cell counts and negative Gram stains, all positive bacterial cultures are contaminants and patient follow-up is unnecessary. We retrospectively reviewed 191 ED charts of patients with positive CSF cultures over 5 years. We abstracted lumbar puncture results, disposition, and follow-up activities, and determined monetary charges. There were 137 patients (72%) who met inclusion criteria with CSF white blood cells ≤7 μL, negative Gram stain, and immunocompetence. Ninety-eight were discharged from the ED and 39 were admitted to the hospital for reasons other than meningitis. All 137 positive cultures were found to be contaminants, with coagulase-negative staphylococci found most commonly. Follow-up activities included telephone calls (49%), repeat ED visits (13%), repeat lumbar punctures (9%), unnecessary antibiotic treatment (6%), and hospitalizations (6%), generating $55,000 in charges. Follow-up may be unnecessary in ED patients with positive bacterial CSF cultures who were discharged from the ED, if their initial lumbar punctures were normal. [Copyright &y& Elsevier]

Context Lead, mercury, and arsenic intoxication have been associated with the use of Ayurvedic herbal medicine product (HMPs). Objectives To determine the prevalence and concentration of heavy metals in Ayurvedic HMPs manufactured in South Asia and sold in Boston-area stores and to compare estimated daily metal ingestion with regulatory standards. Design and Setting Systematic search strategy to identify all stores 20 miles or less from Boston City Hall that sold Ayurvedic HMPs from South Asia by searching online Yellow Pages using the categories markets, supermarkets, and convenience stores, and business names containing the word India, Indian cities, and Indian words. An online national directory of Indian grocery stores, a South Asian community business directory, and a newspaper were also searched. We visited each store and purchased all unique Ayurvedic HMPs between April 25 and October 24, 2003. Main Outcome Measures Concentrations (μg/g) of lead, mercury, and arsenic in each HMP as measured by x-ray fluorescence spectroscopy. Estimates of daily metal ingestion for adults and children estimated using manufacturers’ dosage recommendations with comparisons to US Pharmacopeia and US Environmental Protection Agency regulatory standards. Results A total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained heavy metals: lead (n = 13; median concentration, 40 μg/g; range, 5-37 000), mercury (n = 6; median concentration, 20 225 μg/g; range, 28-104 000), and/or arsenic (n = 6; median concentration, 430 μg/g; range, 37-8130). If taken as recommended by the manufacturers, each of these 14 could result in heavy metal intakes above published regulatory standards. Conclusions One of 5 Ayurvedic HMPs produced in South Asia and available in Boston South Asian grocery stores contains potentially harmful levels of lead, mercury, and/or arsenic. Users of Ayurvedic medicine may be at risk for heavy metal toxicity, and testing of Ayurve... [ABSTRACT FROM AUTHOR]

The prompt response to bortezomib observed in a 63-year-old woman with multiple myeloma was associated with a significant increase in alkaline phosphatase (ALP). After similar elevations were noted in patients responding to bortezomib, thalidomide, dexamethasone combination, ALP levels were analysed in two large bortezomib trials. A statistically significant elevation of ALP from baseline was observed in responding patients (complete and partial responders) within three cycles of therapy. The rise in ALP after bortezomib in three patients was explained by a parallel increase in bone-specific ALP and parathyroid hormone, suggesting that response to bortezomib in myeloma is closely associated with osteoblastic activation. [ABSTRACT FROM AUTHOR]

An all‐solution‐processed transparent conductive electrode with sheet resistance one order of magnitude smaller than conventional nanowire‐based transparent conductors has been developed. This is achieved by integrating all‐solution produced microwires with a nanowire solution and electroplating and electrowelding. Advantages of the resulting transparent conductor are indium‐free, vacuum‐free, and lithographic‐facility‐free, and metallic‐mask‐free, with small domain size (≈10 μm2), low sheet resistance (Rs < 1 Ω □−1), high optical transmittance (T > 80%), mechanical flexibility, and scalability, thus making it an excellent replacement for ITO. [ABSTRACT FROM AUTHOR]