bluuebunny/crossref_metadata_2025 huggingface dataset:
Using expert elicitation to estimate the potential impact of improved diagnostic performance of laboratory tests: a case study on rapid discharge of suspected non–ST elevation myocardial infarction patients
Authors: Kip Michelle MA , Steuten Lotte MG , Koffijberg Hendrik , IJzerman Maarten J , Kusters Ron
Published: October 2016

Early health technology assessment can provide insight in the potential cost‐effectiveness of new tests to guide further development decisions. This can increase their potential benefit but often requires evidence which is lacking in early test development stages. Then, expert elicitation may be used to generate evidence on the impact of tests on patient management. This is illustrated in a case study on a new triple biomarker test (copeptin, heart‐type fatty acid binding protein, and high‐sensitivity troponin [HsTn]) at hospital admission. The elicited evidence enables estimation of the impact of using the triple biomarker on time to exclusion of non–ST elevation myocardial infarction compared with current serial HsTn measurement (performed 0, 2, and 6 h after admission). Cardiologists were asked to estimate the effect of the triple biomarker on patient's discharge rates and interventions performed, depending on its diagnostic performance. This elicited evidence was combined with Dutch reimbursement data and published evidence into a decision analytic model. Direct hospital costs and patients' discharge rates were assessed for 3 testing strategies including this triple biomarker (ie, only at admission or combined with HsTn measurements after 2 and 6 h). Direct hospital costs of suspected non–ST elevation myocardial infarction patients using serial HsTn measurements are estimated at €1825 per patient. Combining this triple biomarker with HsTn measurements after 2 and 6 hours is expected to be the most cost‐effective strategy. Depending on the diagnostic performance of the triple biomarker, this strategy is estimated to reduce costs with €66 to €205 per patient (ie, 3.6%‐11.3% reduction). Expert elicitation can be a valuable tool for early health technology assessment to provide an initial estimate of the cost‐effectiveness of new tests prior to their implementation in clinical practice. As demonstrated in our case study, improved diagnostic performance of the triple biomarker may have benefits that should be further explored.
Analyst Herding and Stock Price Crash Risk: Evidence from China
Authors: Xu Nianhang , Jiang Xuanyu , Chan Kam C. , Wu Shinong
Published: October 2016

We examine the proposition that firms with disproportionately more analysts herding in their coverage, as measured by a larger herding index value, have higher crash risk. Our findings are consistent with the main proposition. The results suggest that information production, rather than monitoring, is the primary mechanism behind the positive relation between herding and crash risk. Our conclusion is robust to different measures of crash risk, crash risk windows, herding measures, subsamples, and instrumental estimation. In addition, using post‐earnings announcement drift, we report that analyst herding slows down bad news transmission in the market. Our findings extend the literature by documenting that analyst herding plays a role in enhancing crash risk. Analyst herding has economic consequences on the covered firms. We offer support for the concern in the literature regarding analyst herding and market fluctuations.
Immunoglobulin M indirect‐fluorescent antibody test for the diagnosis of acute toxoplasmosis during pregnancy in the avidity era: A 14‐year experience at the Tuscany Reference Center for Infectious Diseases in Pregnancy, Florence, Italy
Authors: Trotta Michele , Borchi Beatrice , Zammarchi Lorenzo , Sterrantino Gaetana , Brogi Michela , Kiros Seble Tekle , Lorini Chiara , Bonaccorsi Guglielmo , Colao Maria Grazia , Bartoloni Alessandro
Published: October 2016

Aim

The aim of this study was to evaluate immunoglobulin M indirect‐fluorescent antibody test (IgM IFAT) for the diagnosis of acute or chronic Toxoplasma infection in pregnancy.

Methods

Pregnant women with suspected acute toxoplasmosis referred to the Tuscany Reference Center for Infectious Diseases in Pregnancy during the period 1998–2012 were retrospectively enrolled. All women were tested with a panel of serological tests, including enzyme‐linked immunosorbent assay for IgG avidity and IgM IFAT. On the basis of anamnestic, clinical, and serological criteria, pregnant women were classified into three groups: recently infected (RI), latently infected (LI), and doubtful latently infected (DLI). Patients classified as DLI were excluded from the analysis. The association between IgM IFAT (positive or negative) and the diagnosis of infection (acute or chronic) was assessed. Positive predictive value and negative predictive value of the IgM IFAT were calculated.

Results

A total of 810 pregnant women were enrolled in the study: 302 in the RI group and 508 in the LI group. Fifty‐two women classified as DLI were excluded. IgM IFAT was positive in 172 out of 302 (56.9%) pregnant women in the RI group and in 29 out of 508 (5.7%) in the LI group. The positive predictive value and negative predictive value of IgM IFAT in predicting RI was 85.6% and 78.6%, respectively.

Conclusion

IgM IFAT has reasonable sensitivity and specificity in diagnosing recent infection and, mostly in case of borderline avidity test, could be considered as a further aid for an accurate diagnosis of acute toxoplasmosis in pregnancy.
Thrombelastography coagulation index may be a predictor of venous thromboembolism in gynecological oncology patients
Authors: Liu Jingfu , Wang Na , Chen Yujuan , Lu Rong , Ye Xianren
Published: October 2016

Aim

Venous thromboembolism (VTE) is a well‐recognized complication in gynecological oncology patients, and has an impact on the overall outcome. The purpose of this study was to identify whether thrombelastography (TEG) predicts VTE in gynecological oncology patients.

Methods

This retrospective study included patients with gynecological oncology who were hospitalized at the Fujian Provincial Cancer Hospital from May 2014 to April 2016. Univariate and logistic regression multivariate analyses were performed to determine the clinical and laboratorial factors for VTE in gynecological oncology patients. The sensitivity and specificity of predictors was calculated using receiver operating characteristic curve.

Results

The study included 376 patients; 39 (10.37%) developed VTE. Logistic regression multivariate analysis revealed that TEG coagulation index (CI) value, D‐dimer, arrhythmia, coronary heart disease, surgery within four weeks and chemotherapy within four weeks were independent risk factors for VTE. The area under the curve values were 0.71 (95% confidence interval 0.63–0.79, P = 0.000) for TEG CI and 0.67 (95% confidence interval 0.58–0.76, P = 0.000) for D‐Dimer. The TEG CI cut‐off value was 2.55, which had 53.8% sensitivity and 75.4% specificity for VTE.

Conclusions

These results indicated that the TEG CI value may be predictive of VTE in gynecological oncology patients.
Validity of administrative data for identification of obstructive sleep apnea
Authors: Laratta Cheryl R. , Tsai Willis H. , Wick James , Pendharkar Sachin R. , Johannson Kerri A. , Ronksley Paul E.
Published: October 2016

Obstructive sleep apnea (OSA) is a common condition associated with significant morbidity and health‐care utilization. We determined the validity of an algorithm derived from administrative data for identifying OSA using the respiratory disturbance index (RDI) as the reference standard. We conducted a retrospective cohort study of adults in Alberta, Canada referred for facility and community‐based sleep diagnostic testing between July 2005 and August 2007. Validity indices were estimated for several case definitions of OSA derived from outpatient physician billing claims and hospital discharge codes. For each algorithm, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated against several reference standards for OSA (RDI ≥ 5 h−1, RDI ≥ 15 h−1 or RDI ≥ 30 h−1). For the 2149 patients included in the study, an algorithm requiring one hospital discharge code or two outpatient billing claims identifying OSA in a 2‐year period had a sensitivity of 24.1%, specificity of 67.8%, PPV of 74.8% and NPV of 18.3% (reference standard RDI ≥ 5 h−1). When comorbidities were included in the case definition, the specificity was 90.5% and PPV was 83.3% (reference standard RDI ≥ 5 h−1). Similar findings were observed using RDI ≥ 15 h−1 and ≥30 h−1 as the reference standard. We identify a claims‐based algorithm that identifies OSA with a high degree of specificity in patients referred for sleep diagnostic testing. This validated algorithm has a good PPV and may be useful when identifying patients with OSA for population studies within a single‐payer health‐care system.
The bigger they are the better they taste: size predicts predation risk and anti‐predator behavior in giant clams
Authors: Johnson G. C. , Karajah M. T. , Mayo K. , Armenta T. C. , Blumstein D. T.
Published: October 2016

The decision to hide from predators and the time allocated to hiding are economic decisions that integrate the benefits of escaping a predator and the costs of reduced resource acquisition. Body size is a factor that influences many antipredator decisions. Giant clams, Tridacna maxima, depend on photosynthesis as their main source of energy; thus, retracting their mantle into their shell inhibits energy acquisition and ultimately growth. We experimentally encouraged 95 individual clams to hide by touching them and found that after accounting for variation explained by observer, larger clams remained closed longer. When we looked at the response of these 95 clams to a total of four consecutive experimentally induced closings over about 10 min, we found that larger clams on average hid longer and that clams had individually consistent hiding times and generally habituated to repeated experiments. We then focused on a subset of 30 clams and continued this experiment every other day over 6 days for a total of four sessions. Over this longer duration, clams consistently habituated to repeated disturbance, but the effect of size disappeared. We also found that larger clams were bitten by predators more often than smaller clams. Large clams pay an immediate cost to hiding from benign stimuli and apparently learn to modify their behavior to repeated benign experiences.
Skin permeation of econazole nitrate formulated in an enhanced hydrophilic multiple emulsion
Authors: Suñer‐Carbó Joaquim , Boix‐Montañés Antonio , Halbaut‐Bellowa Lyda , Velázquez‐Carralero Nelvis , Zamarbide‐Ledesma Joanna , Bozal‐de‐Febrer Nuria , Calpena‐Campmany Ana Cristina
Published: October 2016

Local delivery of imidazolic antifungals is limited by its extreme lipophilicity. Multiple emulsions (ME) are a potential vehicle to enhance the delivery of econazole nitrate (ECN), an antifungal targeted to deep‐seated epidermal yeast infections. An 1% ECN hydrophilic ME was compared with a commercial formulation in terms of rheology, droplet size and in vitro antifungal activity against Candida species. Comparative in vitro drug release, human skin permeation and drug retention were investigated using vertical diffusion cells. Rheology demonstrated a pseudoplastic shear thinning with thixotropy facilitating skin residence. No significant aggregation or droplet size variations were observed during a 6‐month stability storage. Both formulations exhibited similar release levels achieving asymptotic values in 5 h. ECN skin permeation levels from the multiple emulsion resulted to be significantly higher than those of the commercial formulation, attributable to differences in formulation polarity and excipients composition. Conversely, similar drug accumulation levels in skin were obtained (40‐130 ppm). These concentrations resulted to be comparable with obtained MIC values (2‐78 ppm), confirming the in vitro antimicrobial efficacy of both formulations. A similar skin retention and a higher permeation rate over the existing formulations is considered an improved approach to target the drug to deep epidermis.
The state of renal replacement therapy for children in South Africa: Data from the first report of the re‐established National Renal Registry
Authors: van Biljon Gertruida , Karusseit Victor O.L.
Published: October 2016

Background

The South African Renal Registry (SARR) was re‐established in 2010. The first report was produced in 2014. It revealed that only 3182 patients out of 43.6 million people who were dependent on the state for medical care, received renal replacement therapy (RRT) in 2012 (73 per million population).

Aim

To describe the state of RRT for children in South Africa in 2012.

Methods

From the SARR report and 2012 dataset, a cross‐sectional study was performed of children under 14 years of age who received chronic dialysis, and incident renal transplants in 2012. Patient demographics, treatment modalities and outcome were recorded and RRT rates computed.

Results

Fifty‐nine children received dialysis in South Africa in 2012, a rate of 3.8 per million age‐related population (pmarp). The mean age was 9 years 11 months. The most common cause of end stage renal failure (ESRF) was acquired glomerular disorders (83%). Ninety percent of the children received treatment in two of the nine provinces. Six children (10%) were treated in the only private dialysis unit. Eleven patients received kidney transplants (19%): six private and five public sector patients. Sixteen patients (27.1%) died: seven due to cardiovascular and three due to cerebrovascular events.

Conclusion

There was a low RRT rate of 3.8 pmarp for children in South Africa in 2012. Private sector patients were likely to receive more optimal treatment. The poor performance of the state health sector can largely be ascribed to a deficiency of funding for RRT facilities and trained personnel.
Therapist competencies necessary for the delivery of compassion‐focused therapy: A Delphi study
Authors: Liddell Alice E. , Allan Steven , Goss Ken
Published: October 2016

Objectives

Compassion‐focused therapy (CFT) has shown promising results for a range of clinical presentations. This study explored the therapeutic competencies required to deliver CFT and organized these into a coherent framework.

Design

The Delphi method was used to explore and refine competencies for delivering CFT in three rounds of data collection.

Methods

The first round involved interviews with 12 experts in CFT. Data were analysed using template analysis to generate a draft competency framework. The main competencies were used to create a survey for rounds two and three involving CFT experts and practitioners. Data collected from the surveys were used to refine the competencies.

Results

The CFT competency framework (CFT‐CF) that was produced comprised 25 main competencies within six key areas of competence. The areas were as follows: competencies in creating safeness, meta‐skills, non‐phase‐specific skills, phase‐specific skills, knowledge and understanding and use of supervision. The main competencies included several subcompetencies specifying knowledge, skills and attributes needed to demonstrate the main competence. Overall, there was consensus on 14 competencies and 20 competencies exceeded an 80% agreement level.

Conclusions

Some of the CFT competencies overlapped with existing therapies, whilst others were specific to CFT. The CFT‐CF provides useful guidance for clinicians, supervisors and training programmes. Further research could develop the CFT‐CF into a therapist rating scale in order to measure the outcome of training and to assess treatment fidelity in clinical trials.

Practitioner points

The compassion‐focused therapy competency framework (CFT‐CF) identifies therapeutic competencies that overlap with existing treatments as well as those specific to compassion‐focused therapy (CFT).

The CFT‐CF builds guidance for the competencies required to deliver CFT in a range of clinical settings.

The CFT‐CF provides guidance for those training CFT therapists.

The CFT‐CF could be used as a basis to develop a therapist rating scale.
Integrated analysis of rice transcriptomic and metabolomic responses to elevated night temperatures identifies sensitivity‐ and tolerance‐related profiles
Authors: Glaubitz Ulrike , Li Xia , Schaedel Sandra , Erban Alexander , Sulpice Ronan , Kopka Joachim , Hincha Dirk K. , Zuther Ellen
Published: October 2016

Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein–protein interactions, jasmonate response and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall‐related genes, of ABA signaling and secondary metabolism. Additionally, metabolite profiles revealed a highly activated TCA cycle under HNT and concomitantly increased levels in pathways branching off that could be corroborated by enzyme activity measurements. Integrated data analysis using clustering based on one‐dimensional self‐organizing maps identified two profiles highly correlated with HNT sensitivity. The sensitivity profile included genes of the functional bins abiotic stress, hormone metabolism, cell wall, signaling, redox state, transcription factors, secondary metabolites and defence genes. In the tolerance profile, similar bins were affected with slight differences in hormone metabolism and transcription factor responses. Metabolites of the two profiles revealed involvement of GABA signaling, thus providing a link to the TCA cycle status in sensitive cultivars and of myo‐inositol as precursor for inositol phosphates linking jasmonate signaling to the HNT response specifically in tolerant cultivars.
Provoked and spontaneous confabulations in Alzheimer's disease: An examination of their prevalence and relation with general cognitive and executive functioning
Authors: El Haj Mohamad , Larøi Frank
Published: October 2016

Aim

A dissociation can be made between confabulations that are produced when the subject is directly questioned (i.e., provoked confabulations) and context‐free, unprovoked confabulations (i.e., spontaneous confabulations). Unlike provoked confabulations, there is a paucity of research on spontaneous confabulations in Alzheimer's disease (AD). Our paper assessed this issue by assessing both types of confabulation in participants with mild to moderate AD and controls.

Methods

Provoked confabulations were evaluated with questions probing personal and general knowledge, whereas spontaneous confabulations were rated by nursing and medical staff.

Results

Findings showed more provoked confabulations in AD participants than in controls. Only occasional appearance of spontaneous confabulations was observed in the AD participants. Further, spontaneous confabulations in AD participants were significantly correlated with general cognitive functioning, but not with executive functioning.

Conclusion

Our findings suggest that spontaneous confabulations in AD are relatively rare, at least in the mild to moderate stage of the disease.
Natural Properties, Necessary Connections, and the Problem of Induction
Authors: Hildebrand Tyler
Published: October 2016

The necessitarian solution to the problem of induction involves two claims: first, that necessary connections are justified by an inference to the best explanation; second, that the best theory of necessary connections entails the timeless uniformity of nature. In this paper, I defend the second claim. My arguments are based on considerations from the metaphysics of laws, properties, and fundamentality.
Placental metabolism: substrate requirements and the response to stress
Authors: Vaughan OR , Fowden AL
Published: October 2016

Contents

The placenta is a dynamic, metabolically active organ with significant nutrient and energy requirements for growth, nutrient transfer and protein synthesis. It uses a range of substrates to meet its energy needs and has a higher rate of oxygen (O2) consumption than many other foetal and adult tissues. Placental metabolism varies with species and alters in response to a range of nutritional and endocrine signals of adverse environmental conditions. The placenta integrates these signals and adapts its metabolic phenotype to help maintain pregnancy and to optimize offspring fitness by diversifying the sources of carbon and nitrogen available for energy production, hormone synthesis and foeto‐placental growth. The metabolic response of the placenta to adversity depends on the nature, severity and duration of the stressful challenge and on whether the insult is maternal, placental or foetal in origin. This review examines placental metabolism and its response to stresses common in pregnancy with particular emphasis on farm species like the sheep. It also considers the consequences of changes in placental metabolism for the supply of O2and nutrients to the foetus.
Do inhaled corticosteroids protect against lung cancer in patients with COPD? A systematic review
Authors: Raymakers Adam J.N. , McCormick Natalie , Marra Carlo A. , Fitzgerald J. Mark , Sin Don , Lynd Larry D.
Published: October 2016

Inhaled corticosteroids (ICS) are commonly prescribed to COPD patients, particularly those with more advanced stages of the disease. These patients are also at increased risk of lung cancer. A systematic review was undertaken to identify studies that examined the association between lung cancer risk and ICS therapy in COPD patients. The search strategy was created in MEDLINE and extended to EMBASE as well as other relevant databases. Both randomized controlled trials (RCTs) and observational studies were considered for inclusion. Studies were required to have incident lung cancer or deaths from lung cancer as an outcome in order to be included in the review. Six studies met the inclusion criteria. Two observational studies directly addressed the specific research. Four RCTs presented sufficient data to calculate the relative risk of lung cancer in COPD patients. None of the identified RCTs showed a statistically significant association of ICS use with lung cancer risk. Observational studies showed a protective effect from ICS use, particularly at high doses. Given the observational evidence and the low numbers of lung cancer events in the RCTs, these results may be prone to type II error. The observational studies dealt with very specific patient populations and exposure definitions, which might not have adequately captured the complex relationship between ICS exposure and lung cancer risk. Results from RCTs suggest no effect of ICS on the risk of lung cancer. However, results from observational studies suggest the potential that ICS may confer a protective effect, particularly at high doses.
Investigating the mechanisms of glyphosate resistance in goosegrass (Eleusine indica (L.) Gaertn.) by RNA sequencing technology
Authors: Chen Jingchao , Huang Hongjuan , Wei Shouhui , Huang Zhaofeng , Wang Xu , Zhang Chaoxian
Published: October 2016

Glyphosate is an important non‐selective herbicide that is in common use worldwide. However, evolved glyphosate‐resistant (GR) weeds significantly affect crop yields. Unfortunately, the mechanisms underlying resistance in GR weeds, such as goosegrass (Eleusine indica (L.) Gaertn.), an annual weed found worldwide, have not been fully elucidated. In this study, transcriptome analysis was conducted to further assess the potential mechanisms of glyphosate resistance in goosegrass. The RNA sequencing libraries generated 24 597 462 clean reads. De novo assembly analysis produced 48 852 UniGenes with an average length of 847 bp. All UniGenes were annotated using seven databases. Sixteen candidate differentially expressed genes selected by digital gene expression analysis were validated by quantitative real‐time PCR (qRT‐PCR). Among these UniGenes, the EPSPS and PFK genes were constitutively up‐regulated in resistant (R) individuals and showed a higher copy number than that in susceptible (S) individuals. The expressions of four UniGenes relevant to photosynthesis were inhibited by glyphosate in S individuals, and this toxic response was confirmed by gas exchange analysis. Two UniGenes annotated as glutathione transferase (GST) were constitutively up‐regulated in R individuals, and were induced by glyphosate both in R and S. In addition, the GST activities in R individuals were higher than in S. Our research confirmed that two UniGenes (PFK, EPSPS) were strongly associated with target resistance, and two GST‐annotated UniGenes may play a role in metabolic glyphosate resistance in goosegrass.
Minimum number of myosin motors accounting for shortening velocity under zero load in skeletal muscle
Authors: Fusi Luca , Percario Valentina , Brunello Elisabetta , Caremani Marco , Bianco Pasquale , Powers Joseph D. , Reconditi Massimo , Lombardi Vincenzo , Piazzesi Gabriella
Published: October 2016

Key points

Myosin filament mechanosensing determines the efficiency of the contraction by adapting the number of switched ON motors to the load.

Accordingly, the unloaded shortening velocity (V0) is already set at the end of latency relaxation (LR), ∼10 ms after the start of stimulation, when the myosin filament is still in the OFF state.

Here the number of actin‐attached motors per half‐myosin filament (n) during V0 shortening imposed either at the end of LR or at the plateau of the isometric contraction is estimated from the relation between half‐sarcomere compliance and force during the force redevelopment after shortening.

The value of n decreases progressively with shortening and, during V0 shortening starting at the end of LR, is 1–4.

Reduction of n is accounted for by a constant duty ratio of 0.05 and a parallel switching OFF of motors, explaining the very low rate of ATP utilization found during unloaded shortening.

The maximum velocity at which a skeletal muscle can shorten (i.e. the velocity of sliding between the myosin filament and the actin filament under zero load, V0) is already set at the end of the latency relaxation (LR) preceding isometric force generation, ∼10 ms after the start of electrical stimulation in frog muscle fibres at 4°C. At this time, Ca2+‐induced activation of the actin filament is maximal, while the myosin filament is in the OFF state characterized by most of the myosin motors lying on helical tracks on the filament surface, making them unavailable for actin binding and ATP hydrolysis. Here, the number of actin‐attached motors per half‐thick filament during V0 shortening (n) is estimated by imposing, on tetanized single fibres from Rana esculenta (at 4°C and sarcomere length 2.15 μm), small 4 kHz oscillations and determining the relation between half‐sarcomere (hs) compliance and force during the force development following V0 shortening. When V0 shortening is superimposed on the maximum isometric force T0, n decreases progressively with the increase of shortening (range 30–80 nm per hs) and, when V0 shortening is imposed at the end of LR, n can be as low as 1–4. Reduction of n is accounted for by a constant duty ratio of the myosin motor of ∼0.05 and a parallel switching OFF of the thick filament, providing an explanation for the very low rate of ATP utilization during extended V0 shortening.
A Methodology to Analyze the Safety of a Coastal Nuclear Power Plant Against Typhoon External Flooding Risks
Authors: Chen Tian , Joly Antoine , Pan Rong , Ji Ping , Chen Guofei
Published: October 2016

For the protection of a coastal nuclear power plant (NPP) against external flooding hazard, the risks caused by natural events have to be taken into account. In this article, a methodology is proposed to analyze the risk of the typical natural event in China (Typhoon). It includes the simulation of the storm surge and the strong waves due to its passage in Chinese coastal zones and the quantification of the sequential overtopping flow rate. The simulation is carried out by coupling two modules of the hydraulic modeling system TELEMAC-MASCARET from ElectricitØ de France (EDF), the shallow water module (TELEMAC2D) and the spectral wave module (TOMAWAC). As an open-source modeling system, this methodology could still be enriched by other phenomena in the near future to ameliorate its performance in safety analysis of the coastal NPPs in China.
A New Way to Demonstrate the Rainbow
Authors: Ivanov Dragia Trifonov , Nikolov Stefan Nikolaev
Published: October 2016

The rainbow is a beautiful optical phenomenon that has fascinated humankind since antiquity. It is caused by a huge number of water droplets in the atmosphere illuminated by the Sun. Many noted physicists have contributed to the explanation of the rainbow. The wave theory of the rainbow was developed by George Airy, and modern descriptions are based on Mie scattering as developed by Gustav Mie. For educational purposes the simpler theory by Descartes, which is based solely on geometrical optics and is much more accessible, is used.
Maximum Range of a Projectile Thrown from Constant-Speed Circular Motion
Authors: Poljak Nikola
Published: October 2016

The problem of determining the angle θ at which a point mass launched from ground level with a given speed v0 will reach a maximum distance is a standard exercise in mechanics. There are many possible ways of solving this problem, leading to the well-known answer of θ = π/4, producing a maximum range of Dmax=v02/g, with g being the free-fall acceleration. Conceptually and calculationally more difficult problems have been suggested to improve student proficiency in projectile motion, with the most famous example being the Tarzan swing problem. The problem of determining the maximum distance of a point mass thrown from constant-speed circular motion is presented and analyzed in detail in this text. The calculational results confirm several conceptually derived conclusions regarding the initial throw position and provide some details on the angles and the way of throwing (underhand or overhand) that produce the maximum throw distance.
“Uphill” cation transport: A bioinspired photo-driven ion pump
Authors: Zhang Zhen , Kong Xiang-Yu , Xie Ganhua , Li Pei , Xiao Kai , Wen Liping , Jiang Lei
Published: October 2016

Driven by light energy, a bioinspired ion pump can realize the “uphill” ion transport process analogous to the biological system.
Physiological and ecological drivers of early spring blooms of a coastal phytoplankter
Authors: Hunter-Cevera Kristen R. , Neubert Michael G. , Olson Robert J. , Solow Andrew R. , Shalapyonok Alexi , Sosik Heidi M.
Published: October 2016

Drivers of phytoplankton blooms

Despite decades of study, there is little evidence to link increases in phytoplankton growth in response to springtime warming with the dynamics of phytoplankton blooms. This lack of understanding makes it difficult to make predictions about global biogeochemical cycling in response to climate change. Hunter-Cevera
et al.
analyzed over a decade of data collected hourly from the New England shelf between 2003 and 2016 (see the Perspective by Worden and Wilken). Blooms now occur 20 days earlier than at the start of observations, because earlier springtime warming stimulates cell division earlier each year. Nevertheless, despite the shift in timing, predatory organisms in the food chain are still ready to consume the superabundance, which brings the blooms to an abrupt end each year.

Science
, this issue p.
326
; see also p.
287
Dynamic creation and evolution of gradient nanostructure in single-crystal metallic microcubes
Authors: Thevamaran Ramathasan , Lawal Olawale , Yazdi Sadegh , Jeon Seog-Jin , Lee Jae-Hwang , Thomas Edwin L.
Published: October 2016

A shocking transformation for silver

Clever processing of metals leads to technologically useful properties such as increased hardness and ductility. Thevamaranet al.fired specially synthesized silver cubes at a hard piece of silica, which produced a shock wave that dramatically changed the microstructure of the silver. The approach produced an extreme range in grain sizes that is useful for creating bendable yet strong metals.

Science, this issue p.312
Ultrafast electron diffraction imaging of bond breaking in di-ionized acetylene
Authors: Wolter B. , Pullen M. G. , Le A.-T. , Baudisch M. , Doblhoff-Dier K. , Senftleben A. , Hemmer M. , Schröter C. D. , Ullrich J. , Pfeifer T. , Moshammer R. , Gräfe S. , Vendrell O. , Lin C. D. , Biegert J.
Published: October 2016

Acetylene's scission visualized by selfie

Can molecules take pictures of themselves? That is more or less the principle underlying laser-induced electron diffraction (LIED): A laser field strips an electron from a molecule and then sends it back to report on the structure of the remaining ion. Wolter
et al.
applied this technique to acetylene to track the cleavage of its C–H bond after double ionization (see the Perspective by Ruan). They imaged the full structure of the molecule and also distinguished more rapid dissociative dynamics when it was oriented parallel rather than perpendicular to the LIED field.

Science
, this issue p.
308
; see also p.
283
Molecular force spectroscopy with a DNA origami–based nanoscopic force clamp
Authors: Nickels Philipp C. , Wünsch Bettina , Holzmeister Phil , Bae Wooli , Kneer Luisa M. , Grohmann Dina , Tinnefeld Philip , Liedl Tim
Published: October 2016

Many tiny force sensors

Several techniques can measure forces on biomolecules, but the need to connect the molecule to the macroscopic world often limits the rate at which data can be taken. Nickels
et al.
created large arrays of nanoscale force sensors by using DNA origami structures. Single-stranded DNA molecules of different lengths attached to the molecule of interest acted as entropic springs, with shorter strands exerting more force. The authors used their setup to study the bending of DNA induced by the TATA-binding protein.

Science
, this issue p.
305
Predicting the basis of convergent evolution
Authors: Bridgham Jamie T.
Published: October 2016

Convergent adaptive traits do not always arise from the same genetic changes
The first jaws
Authors: Long John A.
Published: October 2016

A fossil fish helps to explain how jaws first evolved
Curli Temper Adherence of Escherichia coli O157:H7 to Squamous Epithelial Cells from the Bovine Recto-Anal Junction in a Strain-Dependent Manner
Authors: Kudva Indira T. , Carter Michelle Q. , Sharma Vijay K. , Stasko Judith A. , Giron Jorge A.
Published: October 2016

Our recent studies have shown that intimin and the locus of enterocyte effacement-encoded proteins do not play a role in
Escherichia coli
O157:H7 (O157) adherence to the bovine recto-anal junction squamous epithelial (RSE) cells. To define factors that play a contributory role, we investigated the role of curli, fimbrial adhesins commonly implicated in adherence to various fomites and plant and human epithelial cells, in O157 adherence to RSE cells. Specifically, we examined (i) wild-type strains of O157; (ii) curli variants of O157 strains; (iii) isogenic curli deletion mutants of O157; and (iv) adherence inhibition of O157 using anti-curlin sera. Results of these experiments conducted under stringent conditions suggest that curli do not solely contribute to O157 adherence to RSE cells and in fact demonstrate a modulating effect on O157 adherence to RSE cells in contrast to HEp-2 cells (
h
uman
ep
idermoid carcinoma of the larynx cells with HeLa contamination). The absence of curli and presence of blocking anti-curli antibodies enhanced O157-RSE cell interactions among some strains, thus alluding to a spatial, tempering effect of curli on O157 adherence to RSE cells when present. At the same time, the presence or absence of curli did not alter RSE cell adherence patterns of another O157 strain. These observations are at variance with the reported role of curli in O157 adherence to human cell lines such as HEp-2 and need to be factored in when developing anti-adherence modalities for preharvest control of O157 in cattle.

IMPORTANCE
This study demonstrated that O157 strains interact with epithelial cells in a host-specific manner. The fimbriae/adhesins that are significant for adherence to human cell lines may not have a role or may have a modulating role in O157 adherence to bovine cells. Targeting such adhesins may not prevent O157 attachment to bovine cells but instead may result in improved adherence. Hence, conducting host-specific evaluations is critical when selecting targets for O157 control strategies.
Use of a Toxin Neutralization Assay To Characterize the Serologic Response to Adenylate Cyclase Toxin after Infection with Bordetella pertussis
Authors: Eby Joshua C. , Gray Mary C. , Warfel Jason M. , Merkel Tod J. , Hewlett Erik L.
Published: October 2016

Adenylate cyclase toxin (ACT) is an essential virulence factor of
Bordetella pertussis
, and antibodies to ACT protect against
B. pertussis
infection in mice. The toxin is therefore a strong candidate antigen for addition to future acellular pertussis vaccines. In order to characterize the functionality of the immunologic response to ACT after infection, we developed an assay for testing the ability of serum samples from subjects infected with
B. pertussis
to neutralize ACT-induced cytotoxicity in J774 macrophage cells. Baboons develop neutralizing anti-ACT antibodies following infection with
B. pertussis
, and all sera from baboons with positive anti-ACT IgG enzyme-linked immunosorbent assay (ELISA) results neutralized ACT cytotoxicity. The toxin neutralization assay (TNA) was positive in some baboon sera in which ELISA remained negative. Of serum samples obtained from humans diagnosed with pertussis by PCR, anti-ACT IgG ELISA was positive in 72%, and TNA was positive in 83%. All samples positive for anti-ACT IgG ELISA were positive by TNA, and none of the samples from humans without pertussis neutralized toxin activity. These findings indicate that antibodies to ACT generated following infection with
B. pertussis
consistently neutralize toxin-induced cytotoxicity and that TNA can be used to improve understanding of the immunologic response to ACT after infection or vaccination.
Taxonomic Changes and Additions for Human and Animal Viruses, 2012 to 2015
Authors: Loeffelholz Michael J. , Fenwick Bradley W.
Published: October 2016

Taxonomical classification of newly discovered viruses and reclassification of previously discovered viruses provide an important foundation for detailing biological differences of scientific and clinical interest. The development of molecular analytical methods has enabled finer levels and more precise levels of classification. Periodically, there is need to refresh the literature and common understanding of current taxonomic classification, which we attempt to do here in addressing changes in human and animal viruses of medical significance between 2012 and 2015.
Clinical Microbiology Laboratories' Adoption of Culture-Independent Diagnostic Tests Is a Threat to Foodborne-Disease Surveillance in the United States
Authors: Shea Shari , Kubota Kristy A. , Maguire Hugh , Gladbach Stephen , Woron Amy , Atkinson-Dunn Robyn , Couturier Marc Roger , Miller Melissa B. , Shea Shari , Kubota Kristy A. , Maguire Hugh , Gladbach Stephen , Woron Amy , Couturier Marc Roger , Miller Melissa B. , Gilligan Peter H.
Published: October 2016

INTRODUCTION

In November 2015, the Centers for Disease Control and Prevention (CDC) sent a letter to state and territorial epidemiologists, state and territorial public health laboratory directors, and state and territorial health officials. In this letter, culture-independent diagnostic tests (CIDTs) for detection of enteric pathogens were characterized as “a serious and current threat to public health surveillance, particularly for Shiga toxin-producing
Escherichia coli
(STEC) and
Salmonella
.” The document says CDC and its public health partners are approaching this issue, in part, by “reviewing regulatory authority in public health agencies to require culture isolates or specimen submission if CIDTs are used.” Large-scale foodborne outbreaks are a continuing threat to public health, and tracking these outbreaks is an important tool in shortening them and developing strategies to prevent them. It is clear that the use of CIDTs for enteric pathogen detection, including both antigen detection and multiplex nucleic acid amplification techniques, is becoming more widespread. Furthermore, some clinical microbiology laboratories will resist the mandate to require submission of culture isolates, since it will likely not improve patient outcomes but may add significant costs. Specimen submission would be less expensive and time-consuming for clinical laboratories; however, this approach would be burdensome for public health laboratories, since those laboratories would need to perform culture isolation prior to typing. Shari Shea and Kristy Kubota from the Association of Public Health Laboratories, along with state public health laboratory officials from Colorado, Missouri, Tennessee, and Utah, will explain the public health laboratories' perspective on why having access to isolates of enteric pathogens is essential for public health surveillance, detection, and tracking of outbreaks and offer potential workable solutions which will allow them to do this. Marc Couturier of ARUP Laboratories and Melissa Miller of the University of North Carolina will explain the advantages of CIDTs for enteric pathogens and discuss practical solutions for clinical microbiology laboratories to address these public health needs.
Rapid Detection and Identification of Candidemia by Direct Blood Culturing on Solid Medium by Use of Lysis-Centrifugation Method Combined with Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS)
Authors: Idelevich Evgeny A. , Grünastel Barbara , Becker Karsten
Published: October 2016

Candida
sepsis is a life-threatening condition with increasing prevalence. In this study, direct blood culturing on solid medium using a lysis-centrifugation procedure enabled successful
Candida
species identification by matrix-assisted laser desorption–ionization time of flight mass spectrometry on average 3.8 h (Sabouraud agar) or 7.4 h (chocolate agar) before the positivity signal for control samples in Bactec mycosis-IC/F or Bactec Plus aerobic/F bottles, respectively. Direct culturing on solid medium accelerated candidemia diagnostics compared to that with automated broth-based systems.
Nonstructural Protein NSs of Schmallenberg Virus Is Targeted to the Nucleolus and Induces Nucleolar Disorganization
Authors: Gouzil Julie , Fablet Aurore , Lara Estelle , Caignard Grégory , Cochet Marielle , Kundlacz Cindy , Palmarini Massimo , Varela Mariana , Breard Emmanuel , Sailleau Corinne , Viarouge Cyril , Coulpier Muriel , Zientara Stéphan , Vitour Damien
Published: October 2016

Schmallenberg virus (SBV) was discovered in Germany in late 2011 and then spread rapidly to many European countries. SBV is an orthobunyavirus that causes abortion and congenital abnormalities in ruminants. A virus-encoded nonstructural protein, termed NSs, is a major virulence factor of SBV, and it is known to promote the degradation of Rpb1, a subunit of the RNA polymerase II (Pol II) complex, and therefore hampers global cellular transcription. In this study, we found that NSs is mainly localized in the nucleus of infected cells and specifically appears to target the nucleolus through a nucleolar localization signal (NoLS) localized between residues 33 and 51 of the protein. NSs colocalizes with nucleolar markers such as B23 (nucleophosmin) and fibrillarin. We observed that in SBV-infected cells, B23 undergoes a nucleolus-to-nucleoplasm redistribution, evocative of virus-induced nucleolar disruption. In contrast, the nucleolar pattern of B23 was unchanged upon infection with an SBV recombinant mutant with NSs lacking the NoLS motif (SBVΔNoLS). Interestingly, unlike wild-type SBV, the inhibitory activity of SBVΔNoLS toward RNA Pol II transcription is impaired. Overall, our results suggest that a putative link exists between NSs-induced nucleolar disruption and its inhibitory function on cellular transcription, which consequently precludes the cellular antiviral response and/or induces cell death.

IMPORTANCE
Schmallenberg virus (SBV) is an emerging arbovirus of ruminants that spread in Europe between 2011 and 2013. SBV induces fetal abnormalities during gestation, with the central nervous system being one of the most affected organs. The virus-encoded NSs protein acts as a virulence factor by impairing host cell transcription. Here, we show that NSs contains a nucleolar localization signal (NoLS) and induces disorganization of the nucleolus. The NoLS motif in the SBV NSs is absolutely necessary for virus-induced inhibition of cellular transcription. To our knowledge, this is the first report of nucleolar functions for NSs within the
Bunyaviridae
family.
Importance of Highly Conserved Peptide Sites of Human Cytomegalovirus gO for Formation of the gH/gL/gO Complex
Authors: Stegmann Cora , Abdellatif Mohamed E. A. , Laib Sampaio Kerstin , Walther Paul , Sinzger Christian
Published: October 2016

The glycoprotein O (gO) is betaherpesvirus specific. Together with the viral glycoproteins H and L, gO forms a covalent trimeric complex that is part of the viral envelope. This trimer is crucial for cell-free infectivity of human cytomegalovirus (HCMV) but dispensable for cell-associated spread. We hypothesized that the amino acids that are conserved among gOs of different cytomegaloviruses are important for the formation of the trimeric complex and hence for efficient virus spread. In a mutational approach, nine peptide sites, containing all 13 highly conserved amino acids, were analyzed in the context of HCMV strain TB40-BAC4 with regard to infection efficiency and formation of the gH/gL/gO complex. Mutation of amino acids (aa) 181 to 186 or aa 193 to 198 resulted in the loss of the trimer and a complete small-plaque phenotype, whereas mutation of aa 108 or aa 249 to 254 caused an intermediate phenotype. While individual mutations of the five conserved cysteines had little impact, their relevance was revealed in a combined mutation, which abrogated both complex formation and cell-free infectivity. C343 was unique, as it was sufficient and necessary for covalent binding of gO to gH/gL. Remarkably, however, C218 together with C167 rescued infectivity in the absence of detectable covalent complex formation. We conclude that all highly conserved amino acids contribute to the function of gO to some extent but that aa 181 to 198 and cysteines 343, 218, and 167 are particularly relevant. Surprisingly, covalent binding of gO to gH/gL is required neither for its incorporation into virions nor for proper function in cell-free infection.

IMPORTANCE
Like all herpesviruses, the widespread human pathogen HCMV depends on glycoproteins gB, gH, and gL for entry into target cells. Additionally, gH and gL have to bind gO in a trimeric complex for efficient cell-free infection. Homologs of gO are shared by all cytomegaloviruses, with 13 amino acids being highly conserved. In a mutational approach we analyzed these amino acids to elucidate their role in the function of gO. All conserved amino acids contributed either to formation of the trimeric complex or to cell-free infection. Notably, these two phenotypes were not inevitably linked as the mutation of a charged cluster in the center of gO abrogated cell-free infection while trimeric complexes were still being formed. Cysteine 343 was essential for covalent binding of gO to gH/gL; however, noncovalent complex formation in the absence of cysteine 343 also allowed for cell-free infectivity.