bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteopathic Medical Students' Understanding of the Patient Protection and Affordable Care Act: A First Step Toward a Policy-Informed Curriculum
Authors: Beverly Elizabeth Ann , Skinner Daniel , Bianco Joseph A. , Ice Gillian H.
Published: February 2015

Context:Current osteopathic medical students will play an important role in implementing, modifying, and advocating for or against the Patient Protection and Affordable Care Act (ACA) of 2010. Accordingly, medical educators will need to address curricular gaps specific to the ACA and medical practice. Research that gauges osteopathic medical students' level of understanding of the ACA is needed to inform an evidence-based curriculum.

Objective:To assess first- and second-year osteopathic medical students' beliefs about the ACA.

Methods:In this descriptive cross-sectional survey-based study, first- and second-year students were recruited because their responses would be indicative of what, if any, information about the ACA was being covered in the preclinical curriculum. A 30-item survey was distributed in November 2013, after the health insurance exchanges launched on October 1, 2013.

Results:A total of 239 first- and second-year osteopathic medical students completed the survey. One hundred ten students (46%) disagreed and 103 (43.1%) agreed that the ACA would provide health insurance coverage for all US citizens. The ACA was predicted to lead to lower wages and fewer jobs (73 students [30.5%]), as well as small business bankruptcy because of employees' health insurance costs (96 [40.2%]). Regarding Medicare recipients, 113 students (47.3%) did not know whether these individuals would be required to buy insurance through the health insurance exchanges. The majority of students knew that the ACA would require US citizens to pay a penalty if they did not have health insurance (198 [82.8%]) and understood that not everyone would be required to purchase health insurance through health insurance exchanges (137 [57.3%]). Although students took note of certain clinical benefits for patients offered by the ACA, they remained concerned about the ACA's impact on their professional prospects, particularly in the area of primary care.

Conclusion:These findings build on the existing literature that emphasize the need for incorporating into the osteopathic medical curriculum knowledge of the dynamics of health care policy and reform and for creating opportunities for students to follow health policy developments as they evolve in real time.
Reliability and Precision of Stress Sonography of the Ulnar Collateral Ligament
Authors: Bica David , Armen Joseph , Kulas Anthony S. , Youngs Kevin , Womack Zachary
Published: February 2015

Objectives

Musculoskeletal sonography has emerged as an additional diagnostic tool that can be used to assess medial elbow pain and laxity in overhead throwers. It provides a dynamic, rapid, and noninvasive modality in the evaluation of ligamentous structural integrity. Many studies have demonstrated the utility of dynamic sonography for medial elbow and ulnar collateral ligament (UCL) integrity. However, evaluating the reliabilityand precision of these measurements is critical if sonography is ultimately used as a clinical diagnostic tool. The purpose of this study was to evaluate the reliability and precision of stress sonography applied to the medial elbow.

Methods

We conducted a cross‐sectional study during the 2011 baseball off‐season. Eighteen National Collegiate Athletic Association Division I pitchers were enrolled, and 36 elbows were studied. Using sonography, the medial elbow was assessed, and measurements of the UCL length and ulnohumeral joint gapping were performed twice under two conditions (unloaded and loaded) and bilaterally.

Results

Intraclass correlation coefficients (0.72–0.94) and standard errors of measurements (0.3–0.9 mm) for UCL length and ulnohumeral joint gapping were good to excellent. Mean differences between unloaded and loaded conditions for the dominant arms were 1.3 mm (gapping; P < .001) and 1.4 mm (UCL length; P < .001).

Conclusions

Medial elbow stress sonography is a reliable and precise method for detecting changes in ulnohumeral joint gapping and UCL lengthening. Ultimately, this method may provide clinicians valuable information regarding the medial elbow's response to valgus loading and may help guide treatment options.
Noninvasive Evaluation of Liver Fibrosis Using Real‐time Tissue Elastography and Transient Elastography (FibroScan)
Authors: Meng Fankun , Zheng Ying , Zhang Qi , Mu Xiaojie , Xu Xiaoluan , Zhang Haiying , Ding Lei
Published: February 2015

Objectives

The purpose of this study was to assess liver fibrosis with real‐time tissue elastography and to compare the results with those of transient elastographic (FibroScan; Echosens, Paris, France) measurements by using liver biopsy as the reference standard.

Methods

Real‐time tissue elastography and percutaneous liver biopsy were performed in 166 patients with chronic hepatitis B (estimation group). The relationship between the parameters obtained via real‐time tissue elastography and the hepatic fibrosis stage was evaluated by a stepwise multiple linear regression, and the regression equation was used to calculate the liver fibrosis index. The diagnostic performance of the liver fibrosis index was validated and compared with FibroScan in 121 other patients with chronic hepatitis B (validation group).

Results

The liver fibrosis index was calculated as follows: liver fibrosis index = 0.043 low‐strain area ratio + 4.520 skewness + 0.033 mean – 1.002 kurtosis. The liver fibrosis index and liver stiffness measured by FibroScan were both significantly associated with the fibrosis stage in the validation group (r= 0.667 and 0.664, respectively; both P< .001). The areas under the receiver operating characteristic curves for the liver fibrosis index and liver stiffness were 0.880 and 0.909 for predicting substantial fibrosis (scores ≥F2), 0.868 and 0.874 for predicting severe fibrosis (≥F3), and 0.752 and 0.815 for predicting cirrhosis (F4), respectively.

Conclusions

Real‐time tissue elastography is an effective method for assessing liver fibrosis, with diagnostic performance similar to that of transient elastography.
External Ultrasound for Carotid Atherosclerotic Plaque Treatment
Authors: Zhang Yan , Dong Honglin , Xu Yuming , Shi Runhua , Gu Jingming , Lang Hongzhi , Gao Jianbo , Zhang Wayne W.
Published: February 2015

Objectives

The purpose of this study was to evaluate the efficacy of external ultrasound in the treatment of carotid atherosclerotic plaques.

Methods

In the prospective study, 357 patients with 363 carotid atherosclerotic plaques were divided into an ultrasound treatment group and a control group. For 30 days, conventional medical treatment was conducted on 54 plaques in the control group, whereas irradiation therapy in addition to conventional medical treatment was conducted on 309 plaques in the ultrasound group. Carotid sonography was conducted before and after treatment, and the maximum plaque thickness and area were measured in a longitudinal section.

Results

No patients withdrew from the treatment because of related side effects. After treatment, the maximum thickness and area of 79.94% of the plaques in the ultrasound group were reduced, whereas in the control group, the thickness and area of 18.52% were reduced. The mean changes in plaque thickness and area ± SD in the ultrasound and control groups were 0.22 ± 0.19 mm (7.61% ± 5.67%) versus 0.02 ± 0.05 mm (0.74% ± 1.64%) and 0.047 ± 0.039 cm2 (13.28% ± 9.8%) versus 0.0044 ± 0.0102 cm2 (1.1% ± 2.46%), respectively. Changes in both plaque thickness and area in the ultrasound group were significantly greater than those in the control group (P< .0001). Furthermore, the plaque echo type was another prognostic factor affecting efficacy (P < .05).

Conclusions

External ultrasound treatment is safe and effective for carotid atherosclerotic plaques and is worthy of further research and applications. The efficacy in anechoic/hypoechoic plaques is significantly higher than that in mixed echoic and calcified echoic plaques.
Association of Common Carotid Artery Doppler‐Determined Dicrotic Notch Velocity With the Left Ventricular Ejection Fraction
Authors: Polak Joseph F. , Alessi-Chinetti Jean M. , Patel Ayan R. , Estes James M.
Published: February 2015

Objectives

The appearance of the dicrotic notch on blood pressure tracings is associated with impaired cardiac function. Common carotid artery waveforms have similar fiduciary markers, yet they have not been related to cardiac function. We studied associations of common carotid artery dicrotic notch velocities with the left ventricular ejection fraction (LVEF) determined by echocardiography.

Methods

We conducted a retrospective study of 37 patients who had cardiac echocardiography and carotid Doppler evaluations within 1 day of each other. The LVEF was determined by the biplane modified Simpson rule. Doppler parameters were measured from tracings of the left common carotid artery 4 cm from the flow divider. Linear regression and stepwise multivariable linear regression models were used to evaluate any association between the LVEF and the following variables: age, sex, peak systolic velocity (PSV), end‐diastolic velocity (EDV), dicrotic notch velocity, rise time (EDV to PSV), resistive index, and cardiac cycle length.

Results

The dicrotic notch velocity was the only variable associated with the LVEF (P = .028) in a bivariate analyses. A backward selection stepwise multivariable equation predicting the LVEF had the dicrotic notch (P = .001) and resistive index (P = .01) as significant predictors, whereas the cardiac cycle length (P = .08) and PSV (P = .08) were borderline not significant. Model goodness of fit was R2 = 0.37 (P = .004).

Conclusions

Dicrotic notch velocities measured from common carotid artery Doppler waveforms are associated with the LVEF and might offer some clinical value in selected cases.
Characterization of Coronary Flow Reserve and Left Ventricular Remodeling in a Mouse Model of Chronic Aortic Regurgitation With Carvedilol Intervention
Authors: Wang Xiangfei , Wu Jian , Zhu Dan , You Jieyun , Zou Yunzeng , Qian Juying , Ge Junbo
Published: February 2015

Objectives

We hypothesized that left ventricular (LV) remodeling might be exaggerated by an impaired coronary flow reserve in mice with chronic severe aortic regurgitation, and carvedilol, a β‐adrenoceptor blocker, could regress the course.

Methods

Severe aortic regurgitation was induced by retrograde puncture of the aortic valve leaflets under sonographic guidance in 12‐week‐old male C57BL/6J mice. Four weeks after regurgitation, the mice were treated with carvedilol (30 mg/kg/d) or not treated (control). Before and 4 weeks after carvedilol treatment, the coronary flow reserve and LV structure and function were evaluated by echocardiography. Cardiomyocytes and fibrosis were validated by histologic analysis.

Results

Four‐week aortic regurgitation caused a decreased LV ejection fraction and an increased LV end‐systolic volume index. Regurgitation also impaired the coronary flow reserve due to an increase in the basal coronary peak diastolic velocity and velocity‐time integral combined with the absence of substantial changes in the hyperemic coronary peak diastolic velocity and velocity‐time integral. Four more weeks of regurgitation further deteriorated LV remodeling and coronary perfusion in the control group. In contrast, the carvedilol‐treated group showed attenuated LV remodeling and a higher coronary flow reserve by decreasing the basal peak diastolic velocity and velocity‐time integral without substantial changes in the hyperemic peak diastolic velocity and velocity‐time integral. The coronary flow reserve and its pretreatment versus posttreatment difference were positively correlated with the pretreatment versus posttreatment LV ejection fraction and end‐systolic volume index differences. In the carvedilol‐treated group, subendocardial fibrosis was significantly reduced (P < .05), and the cardiomyocyte cross‐sectional area tended to be smaller.

Conclusions—

In mice with chronic severe aortic regurgitation, carvedilol therapy significantly improves the impaired coronary flow reserve and sufficiently attenuates adverse LV remodeling. Sustained coronary flow reserve impairment indicates progressive LV remodeling.
Microtopographic and depth controls on active layer chemistry in Arctic polygonal ground
Authors: Newman B. D. , Throckmorton H. M. , Graham D. E. , Gu B. , Hubbard S. S. , Liang L. , Wu Y. , Heikoop J. M. , Herndon E. M. , Phelps T. J. , Wilson C. J. , Wullschleger S. D.
Published: February 2015

Polygonal ground is a signature characteristic of Arctic lowlands, and carbon release from permafrost thaw can alter feedbacks to Arctic ecosystems and climate. This study describes the first comprehensive spatial examination of active layer biogeochemistry that extends across high‐ and low‐centered, ice wedge polygons, their features, and with depth. Water chemistry measurements of 54 analytes were made on surface and active layer pore waters collected near Barrow, Alaska, USA. Significant differences were observed between high‐ and low‐centered polygons suggesting that polygon types may be useful for landscape‐scale geochemical classification. However, differences were found for polygon features (centers and troughs) for analytes that were not significant for polygon type, suggesting that finer‐scale features affect biogeochemistry differently from polygon types. Depth variations were also significant, demonstrating important multidimensional aspects of polygonal ground biogeochemistry. These results have major implications for understanding how polygonal ground ecosystems function, and how they may respond to future change.
Turbulent nitrate fluxes in the Lower St. Lawrence Estuary, Canada
Authors: Cyr Frédéric , Bourgault Daniel , Galbraith Peter S. , Gosselin Michel
Published: February 2015

Turbulent vertical nitrate fluxes were calculated using new turbulent microstructure observations in the Lower St. Lawrence Estuary (LSLE), Canada. Two stations were compared: the head of the Laurentian Channel (HLC), where intense mixing occurs on the shallow sill that marks the upstream limit of the LSLE, and another station located about 100 km downstream (St. 23), more representative of the LSLE mean mixing conditions. Mean turbulent diffusivities and nitrate fluxes at the base of the surface layer for both stations were, respectively (with 95% confidence intervals):
and
. Observations suggest that the interplay between large isopleth heaving near the sill and strong turbulence is the key mechanism to sustain such high turbulent nitrate fluxes at the HLC (two to three orders of magnitude higher than those at Station 23). Calculations also suggest that nitrate fluxes at the HLC alone can sustain primary production rates of
over the whole LSLE, approximately enough to account for a large part of the phytoplankton bloom and for most of the postbloom production. Surfacing nitrates are also believed to be consumed within the LSLE, not leaving much to be exported to the rest of the Gulf of St. Lawrence.
RACORO continental boundary layer cloud investigations: 3. Separation of parameterization biases single‐column model CAM5 simulations of shallow cumulus
Authors: Lin Wuyin , Liu Yangang , Vogelmann Andrew M. , Fridlind Ann , Endo Satoshi , Song Hua , Feng Sha , Toto Tami , Li Zhijin , Zhang Minghua
Published: February 2015

Climatically important low‐level clouds are commonly misrepresented in climate models. The FAst‐physics System TEstbed and Research (FASTER) Project has constructed case studies from the Atmospheric Radiation Measurement Climate Research Facility's Southern Great Plain site during the RACORO aircraft campaign to facilitate research on model representation of boundary‐layer clouds. This paper focuses on using the single‐column Community Atmosphere Model version 5 (SCAM5) simulations of a multi‐day continental shallow cumulus case to identify specific parameterization causes of low‐cloud biases. Consistent model biases among the simulations driven by a set of alternative forcings suggest that uncertainty in the forcing plays only a relatively minor role. In‐depth analysis reveals that the model's shallow cumulus convection scheme tends to significantly under‐produce clouds during the times when shallow cumuli exist in the observations, while the deep convective and stratiform cloud schemes significantly over‐produce low‐level clouds throughout the day. The links between model biases and the underlying assumptions of the shallow cumulus scheme are further diagnosed with the aid of large‐eddy simulations and aircraft measurements, and by suppressing the triggering of the deep convection scheme. It is found that the weak boundary layer turbulence simulated is directly responsible for the weak cumulus activity and the simulated boundary layer stratiform clouds. Increased vertical and temporal resolutions are shown to lead to stronger boundary layer turbulence and reduction of low‐cloud biases.
Climatic uncertainty in Himalayan water towers
Authors: Mishra Vimal
Published: February 2015

The Himalayan water towers (e.g., Indus, Ganges, and Brahmaputra) play a major role in water resource availability and affect a significant population in the South Asia region. Climatic uncertainty in the region not only hampers progress toward process understanding but also decision making. Observational data sets show uncertainty (standard deviation in mean temperature in data sets) of 0.2 to 0.5°C in winter (January‐February‐March‐April) and the monsoon season (June‐July‐August‐September) air temperature. Observational uncertainty in precipitation in the winter and monsoon seasons ranged between 6 and 17% (with respect to ensemble mean seasonal precipitation) in the Indus, Ganges, and Brahmaputra river basins. The Coordinated Regional Climate Downscaling Experiment (CORDEX) South Asia regional climate models (CORDEX‐RCMs) show larger uncertainty (1–3.6°C in temperature and 18–60% in precipitation) than that of the observations. Moreover, RCMs exhibit a large cold bias (6–8°C) and are not able to reproduce the observed warming in the Himalayan water towers. In fact, the CORDEX‐RCMs overestimate observed warming by threefold in Ganges and Brahmaputra basins, which raises a question on their reliability on future warming trends in the region. The CORDEX‐RCMs overestimate the area that experienced significant warming and fail to reproduce precipitation trends in both magnitude as well as direction. In observational data sets, uncertainty in precipitation and air temperature increases with elevation, which may be associated with sparse observations. However, the CORDEX‐RCMs showed larger uncertainty at the lower elevations in both precipitation as well as temperature. The host general circulation models show a better performance in simulating winter climate than the CORDEX‐RCMs, which suggest that an improved representation of elevation may not necessarily improve the model's performance. While observations show significant warming in the Indus basin and decline in the monsoon season precipitation in the Ganges basin, reliability of future climate projections and their impacts on water resources in the region will depend on improvements in the models and observations in coming years.
Observing and modeling the influence of layering on bubble trapping in polar firn
Authors: Mitchell Logan E. , Buizert Christo , Brook Edward J. , Breton Daniel J. , Fegyveresi John , Baggenstos Daniel , Orsi Anais , Severinghaus Jeffrey , Alley Richard B. , Albert Mary , Rhodes Rachael H. , McConnell Joseph R. , Sigl Michael , Maselli Olivia , Gregory Stephanie , Ahn Jinho
Published: February 2015

Interpretation of ice core trace gas records depends on an accurate understanding of the processes that smooth the atmospheric signal in the firn. Much work has been done to understand the processes affecting air transport in the open pores of the firn, but a paucity of data from air trapped in bubbles in the firn‐ice transition region has limited the ability to constrain the effect of bubble closure processes. Here we present high‐resolution measurements of firn density, methane concentrations, nitrogen isotopes, and total air content that show layering in the firn‐ice transition region at the West Antarctic Ice Sheet (WAIS) Divide ice core site. Using the notion that bubble trapping is a stochastic process, we derive a new parameterization for closed porosity that incorporates the effects of layering in a steady state firn modeling approach. We include the process of bubble trapping into an open‐porosity firn air transport model and obtain a good fit to the firn core data. We find that layering broadens the depth range over which bubbles are trapped, widens the modeled gas age distribution of air in closed bubbles, reduces the mean gas age of air in closed bubbles, and introduces stratigraphic irregularities in the gas age scale that have a peak‐to‐peak variability of ~10 years at WAIS Divide. For a more complete understanding of gas occlusion and its impact on ice core records, we suggest that this experiment be repeated at sites climatically different from WAIS Divide, for example, on the East Antarctic plateau.
Role of water vapor and convection‐circulation decoupling in MJO simulations by a tropical channel model
Authors: Ulate Marcela , Zhang Chidong , Dudhia Jimy
Published: February 2015

A tropical channel model failed to simulate an observed MJO event. As a means to find reasons for the failure, model errors in water vapor (qv) and other fields were corrected to different extents by nudging towards a global reanalysis product. An MJO metric was developed to quantify the realism of a simulated MJO event in the amplitude and zonal propagation speed of its precipitation and zonal wind at 850 hPa (U850). Results show that correcting errors in qv alone is necessary and sufficient for a realistic simulation of the MJO event. Correcting errors in other fields is insufficient by itself and unnecessary with water vapor correction. For a realistic MJO simulation, error corrections are needed for qv perturbations of the planetary scales (zonal wave number 1–3) together with its zonal mean in both the lower and middle troposphere. Correcting errors in qv at upper levels, planetary‐scale perturbations of any single zonal wave number, synoptic‐scale perturbations, or temporal/zonal means alone is not sufficient for a realistic MJO simulation. Amplitudes of MJO precipitation and U850 are significantly correlated, but their propagation speeds are not. MJO signals in U850 are easier than those in precipitation to improve by correcting errors in qv. In the absence of MJO intrinsic dynamics, inserted MJO signals in qv in a simulation may create a phantom MJO event in precipitation but not in the circulation. This study confirms the existing knowledge on the importance of qv to MJO simulations, sheds new lights on the role of the qv spatial structure, and presents evidence for possible precipitation‐circulation decoupling in MJO simulations.
How obliquity cycles powered early Pleistocene global ice‐volume variability
Authors: Tabor Clay R. , Poulsen Christopher J. , Pollard David
Published: February 2015

Milankovitch theory proposes that the magnitude of high‐latitude summer insolation dictates the continental ice‐volume response by controlling summer snow melt, thus anticipating a substantial ice‐volume contribution from the strong summer insolation signal of precession. Yet almost all of the early Pleistocene δ18O records' signal strength resides at the frequency of obliquity. Here we explore this discrepancy using a climate‐vegetation‐ice sheet model to simulate climate‐ice sheet response to transient orbits of varying obliquity and precession. Spectral analysis of our results shows that despite contributing significantly less to the summer insolation signal, almost 60% of the ice‐volume power exists at the frequency of obliquity due to a combination of albedo feedbacks, seasonal offsets, and orbital cycle duration differences. Including eccentricity modulation of the precession ice‐volume component and assuming a small Antarctic ice response to orbital forcing produce a signal that agrees with the δ18O ice‐volume proxy records.
Response of Karakoram‐Himalayan glaciers to climate variability and climatic change: A regional climate model assessment
Authors: Kumar Pankaj , Kotlarski Sven , Moseley Christopher , Sieck Kevin , Frey Holger , Stoffel Markus , Jacob Daniela
Published: February 2015

The Karakoram and the Himalayan mountain range accommodate a large number of glaciers and are the major source of several perennial rivers downstream. To interactively describe to response of glaciers to climate change, a glacier parameterization scheme has been developed and implemented into the regional climate model REMO. The scheme simulates the mass balance as well as changes of the areal extent of glaciers on a subgrid scale. The parameterization scheme is for the first time applied to the region. A regional glacier inventory is compiled and is used to initialize glacier area and volume. Over the highly complex and data sparse region, the simulated mass balance largely agrees with observations including the positive Karakoram anomaly. The simulated equilibrium line altitude is well captured although a systematic underestimation is apparent. REMO simulates the glacier‐climate interaction reasonably well; it has clear potential to be used for future climate assessments.
Self‐Doped Conjugated Polymeric Nanoassembly by Simplified Process for Optical Cancer Theragnosis
Authors: Kim Jeonghun , Lee Eugene , Hong Yoochan , Kim Byeonggwan , Ku Minhee , Heo Dan , Choi Jihye , Na Jongbeom , You Jungmok , Haam Seungjoo , Huh Yong‐Min , Suh Jin‐Suck , Kim Eunkyoung , Yang Jaemoon
Published: February 2015

To access smart optical theragnosis for cancer, an easily processable heterocyclic conjugated polymer (poly(sodium3‐((3‐methyl‐3,4‐dihydro‐2H‐thieno[3,4‐b][1,4]dioxepin‐3‐yl)methoxy)propane‐1‐sulfonate), PPDS) nanoassembly is fabricated by a surfactant‐free one‐step process, without the laborious ordinary multicoating process. The conjugated nanoassembly, with a self‐doped structure, provides strong absorbance in the near‐infrared (NIR) range even in a neutral pH medium and exhibits excellent stability (>six months). In addition, the prepared PPDS nanoassembly shows a high photothermal conversion efficiency of 31.4% in organic photothermal nanoparticles. In particular, the PPDS nanoassembly is stably suspended in the biological medium without any additives. Through a simple immobilization with the anti‐CD44 antibody, the prepared biomarker‐targetable PPDS nanoassembly demonstrates specific targeting toward CD44 (expressed in stem‐like cancer cells), allowing NIR absorbance imaging and the efficient targeted photothermal damaging of CD44‐expressing cancer cells, from in vitro 3D mammospheres (similar to the practical structure of tumor in the body) to in vivo xenograft mice tumor models (breast cancer and fibrosarcoma). In this study, the most simplified preparation method is for this organic conjugated polymer‐based nanoassembly by a molecular approach is reported, and demonstrated as a highly promising optical nanoagent for optical cancer theragnosis.
Mild Hyperthermia Enhances Transport of Liposomal Gemcitabine and Improves In Vivo Therapeutic Response
Authors: Kirui Dickson K. , Celia Christian , Molinaro Roberto , Bansal Shyam S. , Cosco Donato , Fresta Massimo , Shen Haifa , Ferrari Mauro
Published: February 2015

Obstructive biological barriers limit the transport and efficacy of cancer nanotherapeutics. Creative manipulation of tumor microenvironment provides promising avenues towards improving chemotherapeutic response. Such strategies include the use of mechanical stimuli to overcome barriers, and increase drug delivery and therapeutic efficacy. The rational use of gold nanorod‐mediated mild hyperthermia treatment (MHT) alters tumor transport properties, increases liposomal gemcitabine (Gem Lip) delivery, and antitumor efficacy in pancreatic cancer CAPAN‐1 tumor model. MHT treatment leads to a threefold increase in accumulation of 80‐nm liposomes and enhances spatial interstitial distribution. I.v. injection of Gem Lip and MHT treatment lead to a threefold increase in intratumor gemcitabine concentration compared to chemotherapeutic infusion alone. Furthermore, combination of MHT treatment with infusion of 12 mg kg−1 Gem Lip leads to a twofold increase in therapeutic efficacy and inhibition of CAPAN‐1 tumor growth when compared to equimolar chemotherapeutic treatment alone. Enhanced therapeutic effect is confirmed by reduction in tumor size and increase in apoptotic index where MHT treatment combined with 12 mg kg−1 Gem Lip achieves similar therapeutic efficacy as the use of 60 mg kg−1 free gemcitabine. In conclusion, improvements in vivo efficacy are demonstrated resulting from MHT treatment that overcome transport barriers, promote delivery, improve efficacy of nanomedicines.
Biocompatible Enzymatic Roller Pens for Direct Writing of Biocatalytic Materials: “Do‐it‐Yourself” Electrochemical Biosensors
Authors: Bandodkar Amay J. , Jia Wenzhao , Ramírez Julian , Wang Joseph
Published: February 2015

The development of enzymatic‐ink‐based roller pens for direct drawing of biocatalytic sensors, in general, and for realizing renewable glucose sensor strips, in particular, is described. The resulting enzymatic‐ink pen allows facile fabrication of high‐quality inexpensive electrochemical biosensors of any design by the user on a wide variety of surfaces having complex textures with minimal user training. Unlike prefabricated sensors, this approach empowers the end user with the ability of “on‐demand” and “on‐site” designing and fabricating of biocatalytic sensors to suit their specific requirement. The resulting devices are thus referred to as “do‐it‐yourself” sensors. The bio­active pens produce highly reproducible biocatalytic traces with minimal edge roughness. The composition of the new enzymatic inks has been optimized for ensuring good biocatalytic activity, electrical conductivity, biocompati­bility, reproducible writing, and surface adherence. The resulting inks are characterized using spectroscopic, viscometric, electrochemical, thermal and microscopic techniques. Applicability to renewable blood glucose testing, epidermal glucose monitoring, and on‐leaf phenol detection are demonstrated in connection to glucose oxidase and tyrosinase‐based carbon inks. The “do‐it‐yourself” renewable glucose sensor strips offer a “fresh,” reproducible, low‐cost biocatalytic sensor surface for each blood test. The ability to directly draw biocatalytic conducting traces even on unconventional surfaces opens up new avenues in various sensing applications in low‐resource settings and holds great promise for diverse healthcare, environmental, and defense domains.
Enhanced Broad Band Photodetection through Piezo‐Phototronic Effect in CdSe/ZnTe Core/Shell Nanowire Array
Authors: Rai Satish C. , Wang Kai , Chen Jiajun , Marmon Jason K. , Bhatt Manish , Wozny Sarah , Zhang Yong , Zhou Weilie
Published: February 2015

The piezo‐phototronic effect is of immense importance for improving the performance of optoelectronic nanodevices. This is accomplished by tuning the charge carrier generation, separation, and transport under the influence of the inner piezopotential. In this paper, a broad band photodetector is demonstrated that is based on II‐VI binary CdSe/ZnTe core/shell nanowire arrays, in which photodetection is greatly enhanced by the piezo‐phototronic effect. The photodetector performance under UV (385 nm), blue (465 nm), and green (520 nm) illumination infers a saturation free response with an intensity variation near two orders of magnitude, where the peak photocurrent (125 μA) is two orders higher at 0.25 kilogram force (kgf) compared to no load (0.71 μA). The resulting (%) responsivity changed by four orders of magnitude. The significant increase in responsivity is believed to arise from: 1) the piezo‐phototronic effect induced by a change in the Schottky barrier height at the Ag–ZnTe junction, and in the type‐II band alignment at the CdSe–ZnTe interfaces, in conjugation with 2) a small lattice mismatch between the CdSe and ZnTe epitaxial layers, which lead to reduced charge carrier recombination. This work thus extends the piezo‐phototronic effect to a group II‐VI binary semiconductor heterostructure and demonstrates the importance of the epitaxial interface in a core/shell nanowire photodetector.
­Fitness impacts of tapeworm parasitism on wild gelada monkeys at Guassa, Ethiopia
Authors: Nguyen Nga , Fashing Peter J. , Boyd Derek A. , Barry Tyler S. , Burke Ryan J. , Goodale C. Barret , Jones Sorrel C.Z. , Kerby Jeffrey T. , Kellogg Bryce S. , Lee Laura M. , Miller Carrie M. , Nurmi Niina O. , Ramsay Malcolm S. , Reynolds Jason D. , Stewart Kathrine M. , Turner Taylor J. , Venkataraman Vivek V. , Knauf Yvonne , Roos Christian , Knauf Sascha
Published: February 2015

Parasitism is expected to impact host morbidity or mortality, although the fitness costs of parasitism have rarely been quantified for wildlife hosts. Tapeworms in the genusTaeniaexploit a variety of vertebrates, including livestock, humans, and geladas (Theropithecus gelada), monkeys endemic to the alpine grasslands of Ethiopia. DespiteTaenia's adverse societal and economic impacts, we know little about the prevalence of disease associated withTaeniainfection in wildlife or the impacts of this disease on host health, mortality and reproduction. We monitored geladas at Guassa, Ethiopia over a continuous 6½ year period for external evidence (cysts or coenuri) ofTaenia‐associated disease (coenurosis) and evaluated the impact of coenurosis on host survival and reproduction. We also identified (through genetic and histological analyses) the tapeworms causing coenurosis in wild geladas at Guassa asTaenia serialis. Nearly 1/3 of adult geladas at Guassa possessed ≥1 coenurus at some point in the study. Coenurosis adversely impacted gelada survival and reproduction at Guassa and this impact spanned two generations: adults with coenuri suffered higher mortality than members of their sex without coenuri and offspring of females with coenuri also suffered higher mortality. Coenurosis also negatively affected adult reproduction, lengthening interbirth intervals and reducing the likelihood that males successfully assumed reproductive control over units of females. Our study provides the first empirical evidence that coenurosis increases mortality and reduces fertility in wild nonhuman primate hosts. Our research highlights the value of longitudinal monitoring of individually recognized animals in natural populations for advancing knowledge of parasite‐host evolutionary dynamics and offering clues to the etiology and control of infectious disease. Am. J. Primatol. 77:579–594, 2015. © 2015 Wiley Periodicals, Inc.
A Smart DNAzyme–MnO2 Nanosystem for Efficient Gene Silencing
Authors: Fan Huanhuan , Zhao Zilong , Yan Guobei , Zhang Xiaobing , Yang Chao , Meng Hongmin , Chen Zhuo , Liu Hui , Tan Weihong
Published: February 2015

DNAzymes hold promise for gene‐silencing therapy, but the lack of sufficient cofactors in the cell cytoplasm, poor membrane permeability, and poor biostability have limited the use of DNAzymes in therapeutics. We report a DNAzyme–MnO2 nanosystem for gene‐silencing therapy. MnO2 nanosheets adsorb chlorin e6‐labelled DNAzymes (Ce6), protect them from enzymatic digestion, and efficiently deliver them into cells. The nanosystem can also inhibit 1O2 generation by Ce6 in the circulatory system. In the presence of intracellular glutathione (GSH), MnO2 is reduced to Mn2+ ions, which serve as cofactors of 10–23 DNAzyme for gene silencing. The release of Ce6 generates 1O2 for more efficient photodynamic therapy. The Mn2+ ions also enhance magnetic resonance contrast, providing GSH‐activated magnetic resonance imaging (MRI) of tumor cells. The integration of fluorescence recovery and MRI activation provides fluorescence/MRI bimodality for monitoring the delivery of DNAzymes.
Electrolytic Macrocyclizations: Scalable Synthesis of a Diazonamide‐Based Drug Development Candidate
Authors: Ding Hui , DeRoy Patrick L. , Perreault Christian , Larivée Alexandre , Siddiqui Arshad , Caldwell Charles G. , Harran Susan , Harran Patrick G.
Published: February 2015

An electrochemical method to synthesize the core macrolactam of diazonamides is described. Large ring‐forming dehydrogenation is initiated by anodic oxidation at a graphite surface. The reaction requires no tailoring of the substrate and occurs at ambient temperature in aqueous DMF in an undivided cell open to air. This unique chemistry has enabled a concise, scalable preparation of DZ‐2384; a refined analog of diazonamide A slated for clinical development as a cancer therapeutic.
Active Targeting of Tumors through Conformational Epitope Imprinting
Authors: Zhang Yan , Deng Chunyue , Liu Sha , Wu Jin , Chen Zhangbao , Li Chong , Lu Weiyue
Published: February 2015

Inspired by the knowledge that most antibodies recognize a conformational epitope because of the epitope’s specific three‐dimensional shape rather than its linear structure, we combined scaffold‐based peptide design and surface molecular imprinting to fabricate a novel nanocarrier harboring stable binding sites that captures a membrane protein. In this study, a disulfide‐linked α‐helix‐containing peptide, apamin, was used to mimic the extracellular, structured N‐terminal part of the protein p32 and then serve as an imprinting template for generating a sub‐40 nm‐sized polymeric nanoparticle that potently binds to the target protein, recognizes p32‐positive tumor cells, and successfully mediates targeted photodynamic therapy in vivo. This could provide a promising alternative for currently used peptide‐modified nanocarriers and may have a broad impact on the development of polymeric nanoparticle‐based therapies for a wide range of human diseases.
Cerium(IV)‐Driven Water Oxidation Catalyzed by a Manganese(V)–Nitrido Complex
Authors: Ma Li , Wang Qian , Man Wai‐Lun , Kwong Hoi‐Ki , Ko Chi‐Chiu , Lau Tai‐Chu
Published: February 2015

The study of manganese complexes as water‐oxidation catalysts (WOCs) is of great interest because they can serve as models for the oxygen‐evolving complex of photosystem II. In most of the reported Mn‐based WOCs, manganese exists in the oxidation states III or IV, and the catalysts generally give low turnovers, especially with one‐electron oxidants such as CeIV. Now, a different class of Mn‐based catalysts, namely manganese(V)–nitrido complexes, were explored. The complex [MnV(N)(CN)4]2− turned out to be an active homogeneous WOC using (NH4)2[Ce(NO3)6] as the terminal oxidant, with a turnover number of higher than 180 and a maximum turnover frequency of 6 min−1. The study suggests that active WOCs may be constructed based on the MnV(N) platform.
(sfi)2Statistics for Innovation – The experience of the Oslo centre in industrial statistics
Authors: Frigessi Arnoldo , Holden Lars , Teigland André
Published: February 2015

Statistics is one of the paramount sciences of the 21st century because of the emergence of the value of data as a key asset for development. It is of fundamental importance to deliver statistical methods and tools for the progress of science and sustainable economic growth. Statistics for Innovation (sfi)2has been, between 2007 and 2014, a centre of excellence providing new statistical methodology for selected Norwegian industries and service providers. In this paper, we trace the history of (sfi)2, describe the way it operated and the type of projects it has run over 8 years. We discuss challenges and the way we tried to overcome them. The purpose of this paper is to share our experience for similar centres, outline the advantages and challenges and indicate some recommendations. Copyright © 2015 John Wiley & Sons, Ltd.
Biomass of invasive plant species as a potential feedstock for bioenergy production
Authors: Van Meerbeek Koenraad , Appels Lise , Dewil Raf , Calmeyn Annelies , Lemmens Pieter , Muys Bart , Hermy Martin
Published: February 2015

Invasive alien species (IAS) are one of the most important drivers of species loss. A series of recent (inter)national policies and guidelines however did not prevent new introductions and further spread of non‐indigenous species. But instead of considering invasive plant species as a burden, the biomass production of IAS can be considered and used as an ecosystem service. To assess the possibilities for bioenergy production of four invasive alien plant species in Europe, Fallopia japonica, Heracleum mantegazzianum, Impatiens glandulifera and Solidago gigantea, we determined their biomass production, gross calorific value and biogas yield. The viability of the propagules after digestion was also tested to assess the dispersal risk related to the bioenergy chain. Fallopia japonica and S. gigantea achieved a high annual biomass yield of 8.6 ton DM per hectare. Impatiens glandulifera and H. mantegazzianum had a lower biomass production (5.8 and 6.0 ton DM ha−1). Without extra inputs or agronomic optimization of the crops, the anaerobic digestion of the studied invasive plant species achieved comparable energy outputs per hectare (28–88 GJ ha−1) as some of the current bioenergy systems. All propagules lost their viability after digestion. The risk of further invasion is thus minimized during the digestion process. However, caution during harvest and transport is required to prevent the spread of new propagules. The energetic valorization of the biomass of IAS can create an economic incentive for habitat restoration of invaded sites and offers the opportunity to reconcile the restoration of the invaded habitats with renewable energy goals. © 2015 Society of Chemical Industry and John Wiley & Sons, Ltd
Perceptions of the living dead: An assessment of knowledge and opinions about whole body donation, its process, and willingness to become cadaveric donors in Pennsylvania
Authors: Larner Sean P. , Mcquone Brian , Schober Justine M. , Loukas Marios , Terrell Mark
Published: February 2015

Despite the many important uses for human cadavers, there is a relative shortage of bodies donated to the scientific community in the United States of America. The purpose of this study was to determine the community's perceptions regarding whole body donation and their willingness to become donors. Moreover, we aimed to investigate people's understanding of the process of whole body donation, and examine their opinions regarding its importance. Individuals in Erie, Pennsylvania were surveyed. Data were collected via a questionnaire, which was offered to friends and family members of patients in the waiting area of the UPMC Hamot Surgery Center. All participants were residents of Erie County. The questionnaire was designed to evaluate knowledge and opinions about whole body donation. A total of 123 people completed the survey. We found people were willing to become whole body donors and understood the importance of this giving act, but lacked understanding about the registration process and the use of donated bodies. Participants revealed the belief that they have the right to decide what is to be done with their bodies after death, but did not indicate specific negative repercussions of becoming whole body donors. In conclusion, our findings indicate that the shortage of cadaveric donors could be due to lack of understanding about whole body donation and the registration process. Clin. Anat. 28:442–448, 2015. © 2015 Wiley Periodicals, Inc.
Activity of second‐generation ALK inhibitors against crizotinib‐resistant mutants in an NPM‐ALK model compared to EML4‐ALK
Authors: Fontana Diletta , Ceccon Monica , Gambacorti‐Passerini Carlo , Mologni Luca
Published: February 2015

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor involved in both solid and hematological tumors. About 80% of ALK‐positive anaplastic large‐cell lymphoma (ALCL) cases are characterized by the t(2;5)(p23;q35) translocation, encoding for the aberrant fusion protein nucleophosmin (NPM)‐ALK, whereas 5% of non‐small‐cell lung cancer (NSCLC) patients carry the inv(2)(p21;p23) rearrangement, encoding for the echinoderm microtubule‐associated protein‐like 4 (EML4)‐ALK fusion. The ALK/c‐MET/ROS inhibitor crizotinib successfully improved the treatment of ALK‐driven diseases. However, several cases of resistance appeared in NSCLC patients, and ALK amino acid substitutions were identified as a leading cause of resistance to crizotinib. Second‐generation ALK inhibitors have been developed in order to overcome crizotinib resistance. In this work, we profiled in vitro the activity of crizotinib, AP26113, ASP3026, alectinib, and ceritinib against six mutated forms of ALK associated with clinical resistance to crizotinib (C1156Y, L1196M, L1152R, G1202R, G1269A, and S1206Y) and provide a classification of mutants according to their level of sensitivity/resistance to the drugs. Since the biological activity of ALK mutations extends beyond the specific type of fusion, both NPM‐ALK‐ and EML4‐ALK‐positive cellular models were used. Our data revealed that most mutants may be targeted by using different inhibitors. One relevant exception is represented by the G1202R substitution, which was highly resistant to all drugs (>10‐fold increased IC50 compared to wild type) and may represent the most challenging mutation to overcome. These results provide a prediction of cross‐resistance of known crizotinib‐resistant mutations against all second‐generation tyrosine kinase inhibitors (TKIs) clinically available, and therefore could be a useful tool to help clinicians in the management of crizotinib‐resistance cases.
Synthesis of Oxazolidinones from Epoxides and Isocyanates Catalyzed by Rare‐Earth‐Metal Complexes
Authors: Wang Peng , Qin Jie , Yuan Dan , Wang Yaorong , Yao Yingming
Published: February 2015

Rare‐earth‐metal complexes stabilized by an amino‐bridged triphenolate ligand showed high efficiency in catalyzing the cycloaddition of isocyanates and epoxides in the presence of NBu4I under mild conditions. This strategy is applicable to both terminal and disubstituted epoxides as well as various isocyanates, and tolerated different types of functional groups. Moreover, it is highly regio‐ and stereoselective, and afforded 3,5‐disubstituted oxazolidinones as the only products in most cases in moderate to good yields.
Hotelling trace criterion as a figure of merit for the optimization of chromatogram alignment
Authors: Soares Edward J. , Yalla Gopal R. , O'Connor John B. , Walsh Kevin A. , Hupp Amber M.
Published: February 2015

We present a methodology for optimization of chromatogram alignment using a class separability measure called the Hotelling trace criterion (HTC). This metric is a multi‐class distance measure that accounts for within‐class and between‐class variation. We chose the correlation optimized warping algorithm as our alignment method and used the HTC to judge the effectiveness of the alignment based on algorithm parameters called segment length and max warp.

Biodiesel feedstock samples representing classes of soy, canola, tallow, waste grease, and hybrid were used in our experiments. Fatty acid methyl esters in each biodiesel were separated using gas chromatography‐mass spectroscopy. The entire data set was baseline corrected, aligned, normalized, and mean‐centered prior to principal components (PCs) analysis. The aligned, baseline corrected data sets were used to compute a figure of merit called warping effect, while the PC‐transformed data sets were used to evaluate the HTC. The segment length and max warp parameters that maximized the warping effect and/or HTC were then determined. Scores plots of pairs of PCs, along with 95% confidence ellipses, were created and analyzed.

The results demonstrated that the parameters derived from maximizing the HTC more effectively aligned the data, as evidenced by better clustering of the biodiesels in the scores plots. This behavior was robust to the number of PCs used in the computation of the HTC. We conclude that the HTC is an objective measure of alignment quality that allows for optimal class separability and can be applied to optimize other methods of chromatogram alignment. Copyright © 2015 John Wiley & Sons, Ltd.