bluuebunny/crossref_metadata_2025 huggingface dataset:
The Presumption of Proportionality
Authors: Rivers Julian
Published: May 2014

This article challenges the assumption that the burden of demonstrating that a limitation of a fundamental right is proportionate rests on the public authority seeking to justify the limitation. After considering the operation of burdens and presumptions in European human rights case‐law it notes the difficulties British domestic courts have had in rigorously applying proportionality tests. It suggests that the concerns which lead judges to weaken the requirement of proportionality would be better met by recognising that certain circumstances give rise to a presumption of proportionality, where the burden of demonstrating disproportionality rests on the right‐holder. Five categories of case in which this applies are proposed, and one which has recently been judicially accepted is rejected. Clarifying the types of case in which a presumption of proportionality applies is a preferable strategy to blurring the standards of justification to be met by those seeking to limit the enjoyment of rights.1
Good Faith and the Ubiquity of the ‘Relational’ Contract
Authors: Campbell David
Published: May 2014

The judgment of Leggatt J in Yam Seng Pte Ltd v International Trade Corporation Ltd shows the common belief that the English law of contract does not have a doctrine of good faith to be mistaken. That law does not have a general principle of good faith, but its doctrine of good faith, articulated through numerous specific duties, is more suitable for the interpretation of contracts according to the intentions of the parties than a general principle which invites the imposition of exogenous standards. That Yam Seng involved a relational contract does not mean that paternalistic exogenous standards should be imposed. It means that the good faith obligations essential even to a commercial contract of this sort must be implied in order to give efficacy to the fundamentally co‐operative contractual relationship.
Species and endosymbiont diversity of Bemisia tabaci (Homoptera: Aleyrodidae) on vegetable crops in Senegal
Authors: Hélène Delatte , Rémy Baudin , Nathalie Becker , Anne‐Laure Girard , Traoré Ramatoulaye Sidebe , Jean‐Michel Lett , Bernard Reynaud
Published: May 2014

Bemisia tabaci‐transmitted geminiviruses are one of the major threats on cassava and vegetable crops in Africa. However, to date, few studies are available on the diversity of B. tabaci and their associated endosymbionts in Africa. More than 28 species have been described in the complex of B. tabaci cryptic species; among them, 2 are invasive pests worldwide: MED and MEAM1. In order to assess the species diversity of B. tabaci in vegetable crops in Senegal, several samplings in different localities, hosts and seasons were collected and analyzed with nuclear (microsatellite) and mitochondrial (COI) markers. The bacterial endosymbiont community was also studied for each sample. Two species were detected: MED Q1 and MEAM1 B. Patterns of MED Q1 (dominance on most of the samples and sites, highest nuclear and mitochondrial diversity and broader secondary endosymbiont community: Hamiltonella, Cardinium, Wolbachia and Rickettsia), point toward a predominant resident begomovirus vector group for MED Q1 on market gardening crops. Furthermore, the lower prevalence of the second species MEAM1 B, its lower nuclear and mitochondrial diversity and a narrower secondary endosymbiont community (Hamiltonella/Rickettsia), indicate that this genetic group is exotic and results from a recent invasion in this area.
Antioxidant Properties of Isolated Compounds from Banana Rhizome
Authors: Kandasamy Saravanan , Baggu Chinnababu , Javagal Manjunatha Rangaswamy , Lingamallu Jaganmohan Rao , Yenamandra Venkateswarlu , Aradhya Somaradhya Mallikarjuna
Published: May 2014

In this study, we attempted to explore banana rhizome (BR) as a source of natural bioactive compounds. Dried BR powder was subjected to sequential extraction using solvents with increasing polarity and studied for antioxidant activities. Chloroform and acetone extracts were selected for isolation and identification of bioactive compounds because of their high antioxidant properties. Antioxidant activity guided fractionation of these extracts yielded 3 compounds. The spectroscopy studies revealed the identity of isolated compounds as 4‐epicyclomusalenone, cycloeucalenol acetate and chlorogenic acid. Polyphenolic compound chlorogenic acid and triterpenoid compounds, 4‐cyclomusalenone and cycloeucalenol acetate displayed multifunctional antioxidant activity.

Practical Application

The isolated compounds namely 4‐epicyclomusalenone, cycloeucalenol acetate and chlorogenic acid have demonstrated their antioxidant properties in different in vitro assay models. The present study indicated that the vast quantity of banana rhizome which was incinerated could be a potential source of natural antioxidant compounds. This can also be used in the food, nutraceutical and pharmaceutical industries.
State of the Art in Gluten‐Free Research
Authors: O'Shea Norah , Arendt Elke , Gallagher Eimear
Published: May 2014

Celiac disease (CD) is widespread and is often under diagnosed. It can affect a variety of genetically susceptible people from the young to the old. Presently, the only treatment for celiac patients is lifelong avoidance of any food, drink, sauce, or dressing containing gluten. Scientists and technologists continue in their quest to improve the quality of gluten‐free products. Their main goal is to create a product of a similar standard to the gluten‐containing products, currently on the market. However, the quality of these products still tends to be poor. Bread products have a low volume, pale crust, crumbly texture, bland flavor and a high rate of staling. Other gluten‐free products contain minimal nutrition and substandard product characteristics, for example, pasta having an inferior texture, sauces which separate more easily. The main focus of this review is to discuss the most recent advances in gluten‐free research which have arisen between the years 2011 and 2013. In particular, the manuscript focuses on ingredients and processing methods which have been documented to develop or improve the processing characteristics and nutritional properties of gluten‐free products.
Simultaneous Determination of 15 Phenolic Constituents of Chinese Black Rice Wine by HPLC‐MS/MS with SPE
Authors: Wang Yutang , Liu Yuanyuan , Xiao Chunxia , Liu Laping , Hao Miao , Wang Jianguo , Liu Xuebo
Published: May 2014

This study established a new method for quantitative and qualitative determination of certain components in black rice wine, a traditional Chinese brewed wine. Specifically, we combined solid‐phase extraction and high‐performance liquid chromatography (HPLC) with triple quadrupole mass spectrometry (MS/MS) to determine 8 phenolic acids, 3 flavonols, and 4 anthocyanins in black rice wine. First, we clean samples with OASIS HLB cartridges and optimized extraction parameters. Next, we performed separation on a SHIM‐PACK XR‐ODS column (I.D. 3.0 mm × 75 mm, 2.2 μm particle size) with a gradient elution of 50% aqueous acetonitrile (V/V) and water, both containing 0.2% formic acid. We used multiple‐reaction monitoring scanning for quantification, with switching electrospray ion source polarity between positive and negative modes in a single chromatographic run. We detected 15 phenolic compounds properly within 38 min under optimized conditions. Limits of detection ranged from 0.008 to 0.030 mg/L, and average recoveries ranged from 60.8 to 103.1% with relative standard deviation ≤8.6%. We validated the method and found it to be sensitive and reliable for quantifying phenolic compounds in rice wine matrices.
Comparison of magnetic resonance spectroscopy and positron emission tomography in detection of tumor recurrence in posttreatment of glioma: A diagnostic meta‐analysis
Authors: Wang Xiaoyue , Hu Xudong , Xie Peng , Li Wanhu , Li Xiaoling , Ma Li
Published: May 2014

It is important to distinguish between tumor recurrence and treatment effects in posttreatment patients with high‐grade gliomas. Several imaging modalities have been reported in differentiating between tumor recurrence and treatment effects. However, there were no consistent conclusions between different studies. We performed a meta‐analysis of 23 studies that compared the diagnostic values of fluorine‐18‐fluorodeoxyglucose (18F‐FDG) and 11C‐methionine (11C‐MET) PET (positron emission tomography) or PET/CT (computed tomography) and magnetic resonance spectroscopy (MRS) in predicting tumor recurrence of gliomas. The pooled estimated sensitivity, specificity, positive likelihood ratios, negative likelihood ratios and summary receiver operating characteristic curves of 18F‐FDG and 11C‐MET PET or PET/CT and MRS in detecting tumor recurrence were calculated. In conclusion, MRS is highly sensitive in the detection of tumor recurrence in glioma.18F‐FDG PET or PET/CT is highly specific in recurrence diagnosis. 11C‐MET does not have noticeable advantage over 18F‐FDG. The current evidence shows no statistical difference between MRS and PET on the accuracy.
Attitudes toward embryo donation among staff at in vitro fertilization clinics
Authors: Wånggren Kjell , Baban Mario , Svanberg Agneta Skoog
Published: May 2014

Objective

To examine attitudes towards embryo donation among staff at in vitro fertilization clinics in Sweden.

Design

Descriptive questionnaire study.

Setting

University‐based in vitro fertilization clinic.

Sample

Study participants were the staff at all in vitro fertilization clinics in Sweden.

Methods

A questionnaire with questions regarding different aspects of embryo donation was sent to the 338 healthcare professionals working at Swedish in vitro fertilization clinics.

Main outcome measures

Attitudes towards embryo donation.

Results

A total of 207 persons (61%) responded to the questionnaire. A majority of the respondents (77%) considered that embryo donation to infertile couples should be permitted in Sweden. Most respondents (76%), and especially the men (96%), stated that it should be possible to donate surplus embryos for research. Forty‐two percent of the respondents agreed with embryo donation to single women. A majority of respondents stated that special requirements with regard to the recipient's age, medical condition and criminal background should potentially be considered. The women stated that there should be special demands made concerning recipients' tobacco (48%) and alcohol abuse (92%). A majority considered that donors should be anonymous to the recipients (66%), but not to the child (9%).

Conclusions

Swedish in vitro fertilization staff have positive attitudes concerning embryo donation to infertile couples and also the use of surplus embryos for research.
Priming for health: gut microbiota acquired in early life regulates physiology, brain and behaviour
Authors: Clarke G , O'Mahony SM , Dinan TG , Cryan JF
Published: May 2014

The infant gut microbiome is dynamic, and radical shifts in composition occur during the first 3 years of life. Disruption of these developmental patterns, and the impact of the microbial composition of our gut on brain and behaviour, has attracted much recent attention. Integrating these observations is an important new research frontier.

Conclusion

Early‐life perturbations of the developing gut microbiota can impact on the central nervous system and potentially lead to adverse mental health outcomes.
The role of the uplift of the Qinghai‐Tibetan Plateau for the evolution of Tibetan biotas
Authors: Favre Adrien , Päckert Martin , Pauls Steffen U. , Jähnig Sonja C. , Uhl Dieter , Michalak Ingo , Muellner‐Riehl Alexandra N.
Published: May 2014

Biodiversity is unevenly distributed on Earth and hotspots of biodiversity are often associated with areas that have undergone orogenic activity during recent geological history (i.e. tens of millions of years). Understanding the underlying processes that have driven the accumulation of species in some areas and not in others may help guide prioritization in conservation and may facilitate forecasts on ecosystem services under future climate conditions. Consequently, the study of the origin and evolution of biodiversity in mountain systems has motivated growing scientific interest. Despite an increasing number of studies, the origin and evolution of diversity hotspots associated with the Qinghai‐Tibetan Plateau (QTP) remains poorly understood. We review literature related to the diversification of organisms linked to the uplift of the QTP. To promote hypothesis‐based research, we provide a geological and palaeoclimatic scenario for the region of the QTP and argue that further studies would benefit from providing a complete set of complementary analyses (molecular dating, biogeographic, and diversification rates analyses) to test for a link between organismic diversification and past geological and climatic changes in this region. In general, we found that the contribution of biological interchange between the QTP and other hotspots of biodiversity has not been sufficiently studied to date. Finally, we suggest that the biological consequences of the uplift of the QTP would be best understood using a meta‐analysis approach, encompassing studies on a variety of organisms (plants and animals) from diverse habitats (forests, meadows, rivers), and thermal belts (montane, subalpine, alpine, nival). Since the species diversity in the QTP region is better documented for some organismic groups than for others, we suggest that baseline taxonomic work should be promoted.
Modelling Cumulus Cloud Shape from a Single Image
Authors: Yuan Chunqiang , Liang Xiaohui , Hao Shiyu , Qi Yue , Zhao Qinping
Published: May 2014

Clouds are important components of the fascinating natural images. However, extracting cloud shapes from images remains a challenging task. This paper presents a calculation method for estimating the shape of a cumulus cloud from a single image suitable for flight simulations and games. The shape of the cloud is assumed to be symmetric. Based on this assumption, the intensities of pixels are correlated with the geometry of a cloud's surface via a simplified single scattering model. A propagation scheme is designed to derive the surface progressively, and mesh editing techniques are used to improve the surface. Finally, the cloud is represented by a particle system. The results show that the proposed method can generate realistic cumulus clouds that are similar to those found in the images in terms of the shape distribution.
Uncertainty Estimation in One‐Dimensional Heat Transport Model for Heterogeneous Porous Medium
Authors: Chang Ching‐Min , Yeh Hund‐Der
Published: May 2014

In many practical applications, the rates for ground water recharge and discharge are determined based on the analytical solution developed by Bredehoeft and Papadopulos (1965) to the one‐dimensional steady‐state heat transport equation. Groundwater flow processes are affected by the heterogeneity of subsurface systems; yet, the details of which cannot be anticipated precisely. There exists a great deal of uncertainty (variability) associated with the application of Bredehoeft and Papadopulos' solution (1965) to the field‐scale heat transport problems. However, the quantification of uncertainty involved in such application has so far not been addressed, which is the objective of this wok. In addition, the influence of the statistical properties of log hydraulic conductivity field on the variability in temperature field in a heterogeneous aquifer is also investigated. The results of the analysis demonstrate that the variability (or uncertainty) in the temperature field increases with the correlation scale of the log hydraulic conductivity covariance function and the variability of temperature field also depends positively on the position.
Evidence‐based medicine in plastic surgery: where did it come from and where is it going?
Authors: Ricci Joseph A. , Desai Naman S.
Published: May 2014

Objectives

Evidence‐based medicine, particularly randomized controlled trials, influence many of the daily decisions within plastic surgery as well as nearly every other medical specialty, and will continue to play a larger role in medicine in the future. Even though it is certainly not a new idea, evidence‐based medicine continues to remain a hot topic among members of the healthcare community. As evidence‐based medicine continues to grow and evolve, it is becoming more important for all physicians to understand the fundamentals of evidence‐based medicine: how evidence‐based medicine has changed, and how to successfully incorporate it into the daily practice of medicine.

Results

Admittedly, the wide acceptance and implementation of evidence‐based medicine has been slower in surgical fields such as plastic surgery given the difficulty in performing large scale blinded randomized controlled trials due to the inherent nature of a surgical intervention as a treatment modality. Despite these challenges, the plastic surgery literature has recently begun to respond to the demand for more evidence‐based medicine.

Conclusions

Today's plastic surgeons are making a concerted embrace evidence‐based medicine by increasing the amount of out of high‐level clinical evidence and should be encouraged to continue to further their endeavors in the field of evidence‐based medicine in the future.
Impact of choice of quality appraisal tool for systematic reviews in overviews
Authors: Pieper Dawid , Mathes Tim , Eikermann Michaela
Published: May 2014

Objective

The question whether the choice of a critical appraisal tool has an impact on the result of the evidence synthesis in systematic reviews has been neglected by research. This is also true for psychometric properties of critical appraisal tools. The objective of the study is to exemplify that in the context of overviews (reviews of reviews).

Methods

Based on a published overview investigating the hospital volume‐outcome relationship in surgery, 32 therein included systematic reviews were independently evaluated with four critical appraisal tools by two reviewers. We rated the relationship on a five‐point rating scale using qualitative evidence synthesis. Measures of reliability and correlation coefficients were calculated.

Results

The result of the evidence synthesis was not dependent on the choice of a critical appraisal tool. Inter‐rater reliability differed depending on the tool, Cohens Kappa ranging from 0.47 to 0.76. There was a high heterogeneity between the two pairs of reviewers.

Conclusion

The choice of a critical appraisal tool has no impact on the result of the evidence synthesis, despite differences in the covered components by each CAT. Further studies should concentrate on investigating psychometric properties and the impact of choice of CATs on the evidence synthesis in other contexts. The high heterogeneity between the two pairs of reviewers, all of them experienced in appraising systematic reviews, indicates a degree of interpretability in the items.
Association between the ABO blood group and risk of common cancers
Authors: Li Bei , Tan Bin , Chen Chunxia , Zhao Li , Qin Li
Published: May 2014

Objective

To investigate the association between five common cancers in western China population and ABO blood group.

Methods

Using the data from West China Hospital, we retrospectively reviewed 5012 patients with five common cancers. Blood groups were obtained from medical records. The control group was represented by 1979 health check‐up examinees. The distributions of ABO blood types of certain cancer patients were investigated to assess the possible correlation between certain cancers and the ABO blood groups. A further meta‐analysis was performed based on the studied results to find potential correlation between the ABO blood types and the risk of diseases.

Results

A 24.5% increased risk was found in gastric cancer cases with blood type A when compared with those with blood type O (OR = 1.245, 95% CI 1.014 to 1.529, P = 0.036) from our data analysis. This association was further confirmed by the meta‐analysis of nine studies (OR = 1.25, 95% CI = 1.12 to 1.39).

Conclusions

Our data suggested that blood type A was associated with gastric cancer.
Introducing a new monitoring manual for home fortification and strengthening capacity to monitor nutrition interventions
Authors: Jefferds Maria Elena D. , Flores‐Ayala Rafael
Published: May 2014

Lack of monitoring capacity is a key barrier for nutrition interventions and limits programme management, decision making and programme effectiveness in many low‐income and middle‐income countries. A 2011 global assessment reported lack of monitoring capacity was the top barrier for home fortification interventions, such as micronutrient powders or lipid‐based nutrient supplements. A Manual for Developing and Implementing Monitoring Systems for Home Fortification Interventions was recently disseminated. It is comprehensive and describes monitoring concepts and frameworks and includes monitoring tools and worksheets. The monitoring manual describes the steps of developing and implementing a monitoring system for home fortification interventions, including identifying and engaging stakeholders; developing a programme description including logic model and logical framework; refining the purpose of the monitoring system, identifying users and their monitoring needs; describing the design of the monitoring system; developing indicators; describing the core components of a comprehensive monitoring plan; and considering factors related to stage of programme development, sustainability and scale up. A fictional home fortification example is used throughout the monitoring manual to illustrate these steps. The monitoring manual is a useful tool to support the development and implementation of home fortification intervention monitoring systems. In the context of systematic capacity gaps to design, implement and monitor nutrition interventions in many low‐income and middle‐income countries, the dissemination of new tools, such as monitoring manuals may have limited impact without additional attention to strengthening other individual, organisational and systems levels capacities.
Preventative lipid‐based nutrient supplements (LNS) and young child feeding practices: findings from qualitative research inHaiti
Authors: Lesorogol Carolyn , Jean‐Louis Sherlie , Green Jamie , Iannotti Lora
Published: May 2014

To prevent undernutrition in an urban slum inHaiti, a lipid‐based nutrient supplement (LNS) was introduced through a randomised control trial. Food supplementation for young child nutrition has a long history in Haiti, but there is little empirical information regarding the effects of supplementation on young child feeding practices. One of the concerns raised by supplementation is that it may disrupt other positive feeding practices such as breastfeeding and use of other complementary foods, with negative consequences for child nutrition. We conducted 29 in‐depth interviews with mother–baby pairs from the three comparison groups: control, 3‐monthLNSsupplementation and 6‐monthLNSsupplementation. Findings from those in the LNS groups indicated high acceptance and satisfaction withLNSand perceptions that it positively affects child health and development.LNSwas integrated into and enhanced ongoing complementary feeding practices. The effects ofLNSuse on duration and perceived quantity of breastfeeding were variable, but generally, breastfeeding was maintained during and after the intervention. Interviews generated insights into beliefs regarding infant and young child feeding practices such as introduction and use of complementary foods, and breastfeeding duration, exclusivity and cessation. Implications for the use ofLNSin public health nutrition programmes are discussed.
Oral L-Arginine Before Resistance Exercise Blunts Growth Hormone in Strength Trained Males
Authors: Forbes Scott C. , Harber Vicki , Bell Gordon J.
Published: May 2014

Acute resistance exercise and L-arginine have both been shown to independently elevate plasma growth hormone (GH) concentrations; however, their combined effect is controversial. The purpose was to investigate the combined effects of resistance exercise and L-arginine supplementation on plasma L-arginine, GH, GH secretagogues, and IGF-1 in strength trained participants. Fourteen strength trained males (age: 25 ± 4 y; body mass: 81.4 ± 9.0 kg; height: 179.4 ± 6.9 cm; and training experience: 6.3 ± 3.4 y) participated in a randomized double-blind crossover design (separated by ~7 days). Subjects reported to the laboratory at 08:00 in a fasted state, consumed L-arginine (ARG; 0.075 g·kg−1 body mass) or a placebo (PLA) before performing an acute bout of resistance exercise (3 sets of 8 exercises, 10 repetitions at ~75% 1RM). Blood samples were collected at rest, before exercise, and at 0, 15, 30, and 60 min of rest-recovery. The ARG condition significantly increased plasma L-arginine concentrations (~120%) while no change was detected in the PLA condition. There were no differences between conditions for GH, GH-releasing hormone, ghrelin, or IGF-1 at any time point. GH-inhibiting hormone was significantly lower in the ARG condition. However, integrated area under the curve for GH was blunted in the ARG condition (L-arginine = 288.4 ± 368.7 vs. placebo = 487.9 ± 482.0 min·ng·mL−1, p < .05). L-arginine ingested before resistance exercise significantly elevated plasma L-arginine concentration but attenuated plasma GH in strength trained individuals despite a lower GHIH. Furthermore our data shows that the GH suppression was not due to a GH or IGF-1 induced autonegative feedback loop.
Molecular-Level Functional Magnetic Resonance Imaging of Dopaminergic Signaling
Authors: Lee Taekwan , Cai Lili X. , Lelyveld Victor S. , Hai Aviad , Jasanoff Alan
Published: May 2014

Watching Brain Molecules

Functional neuroimaging using magnetic resonance imaging (MRI) molecular sensors would be useful for mechanistic analysis of neural systems.

Lee
et al.

(p.
533
) applied MRI-detectable sensors to measure molecular aspects of brain function in conjunction with noninvasive imaging. The molecular sensor revealed a quantitative spatiotemporal map of dopamine release in the ventral striatum, a brain area involved in processing rewards.
Deception by Flexible Alarm Mimicry in an African Bird
Authors: Flower Tom P. , Gribble Matthew , Ridley Amanda R.
Published: May 2014

Trick and Treat

Forked-tailed drongos are a particularly intelligent type of bird found in Africa. Drongos associate with many other bird and mammal species, which can learn to respond to drongo warning calls. Drongos are also exceptional mimics of the other species' alarm calls. Though the increased vigilance across these multi species associations is a benefit to all, drongos sometimes use these calls as ploys to scare associated species away from food, which the drongos then steal. However, without some approach to maintain the effectiveness of this deception, the drongos' ploy would soon be detected.

Flower
et al.

(p.
513
) now show that drongos are able to fool their target species longer by flexibly varying the type of call they give.
Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors
Authors: Katsimpardi Lida , Litterman Nadia K. , Schein Pamela A. , Miller Christine M. , Loffredo Francesco S. , Wojtkiewicz Gregory R. , Chen John W. , Lee Richard T. , Wagers Amy J. , Rubin Lee L.
Published: May 2014

Help the Aged

Muscle function declines with age, as does neurogenesis in certain brain regions. Two teams analyzed the effects of heterochronic parabiosis in mice.

Sinha
et al.

(p.
649
) found that when an aged mouse shares a circulatory system with a youthful mouse, the aged mouse sees improved muscle function, and

Katsimpardi
et al.

(p.
630
) observed increased generation of olfactory neurons. In both cases, Growth Differentiation Factor 11 appeared to be one of the key components of the young blood.
Vibrationally Promoted Dissociation of Water on Ni(111)
Authors: Hundt P. Morten , Jiang Bin , van Reijzen Maarten E. , Guo Hua , Beck Rainer D.
Published: May 2014

Vibrating Water Apart

The main route for producing hydrogen for industrial chemical synthesis is steam reforming, in which water and methane react at high temperatures on nickel catalysts to produce hydrogen and carbon dioxide. For both water and methane, the initial dissociation step can be promoted by the translational energy of a molecule as well as its internal vibrational energy, and fundamental studies of these reactions try to determine the relative contributions of these pathways. Although the methane reaction has been well studied, only recently have lasers been available to excite the higher stretching vibrations of water.

Hundt
et al.

(p.
504
) now report a joint experimental and theoretical study of D
2
O dissociation on the Ni(111) surface. For a given input of energy, vibrational energy was more effective for surmounting the reaction barrier than translational energy.
Category 5 or Tempest in a Teapot?
Falling Behind?
Boom, Bust and the Global Race for Scientific Talent

by Michael S. Teitelbaum

Princeton University Press, Princeton, NJ, 2014. 277 pp. $29.95. ISBN 9780691154664.
Authors: Jaffe Adam B.
Published: May 2014

Examining past claims of crisis and their consequences, Teitelbaum disputes arguments that the United States needs more scientists and engineers.
Nonlinear Optics Pushed to the Edge
Authors: Neshev Dragomir , Kivshar Yuri
Published: May 2014

The edges of small flakes of atomically thin crystals become directly visible at optical wavelengths by doubling the frequency of input infrared light.

[Also see Report by

Yin
et al.

]
Male Scent May Compromise Biomedical Studies
Authors: Grimm David
Published: May 2014

The scent of male researchers may be having a profound impact on everything from animal behavior experiments to human clinical trials.
Seafloor Mining Plan Advances, Worrying Critics
Authors: Gramling Carolyn
Published: May 2014

A company prepares to forge ahead with plans to develop the first deep-sea commercial mine.
Intracellular Antiviral Activity of Low-Dose Ritonavir in Boosted Protease Inhibitor Regimens
Authors: De Nicolò Amedeo , Simiele Marco , Calcagno Andrea , Mohamed Abdi Adnan , Bonora Stefano , Di Perri Giovanni , D'Avolio Antonio
Published: May 2014

Protease inhibitors are largely used for the treatment of HIV infection in combination with other antiretroviral drugs. Their improved pharmacokinetic profiles can be achieved through the concomitant administration of low doses of ritonavir (RTV), a protease inhibitor currently used as a booster, increasing the exposure of companion drugs. Since ritonavir-boosted regimens are associated with long-term adverse events, cobicistat, a CYP3A4 inhibitor without antiviral activity, has been developed. Recently, high intracellular concentrations of ritonavir in lymphocytes and monocytes were reported even when ritonavir was administered at low doses, so we aimed to compare its theoretical antiviral activity with those of the associated protease inhibitors. Intracellular concentrations of ritonavir and different protease inhibitors were determined through the same method. Inhibitory constants were obtained from the literature. The study enrolled 103 patients receiving different boosted protease inhibitors, darunavir-ritonavir 600 and 100 mg twice daily and 800 and 100 mg once daily (
n
= 22 and 4, respectively), atazanavir-ritonavir 300 and 100 mg once daily (
n
= 40), lopinavir-ritonavir 400 and 100 mg twice daily (
n
= 21), or tipranavir-ritonavir 500 and 200 mg twice daily (
n
= 16). According to the observed concentrations, we calculated the ratios between the intracellular concentrations of ritonavir and those of the companion protease inhibitor and between the theoretical viral protease reaction speeds with each drug, with and without ritonavir. The median ratios were 4.04 and 0.63 for darunavir-ritonavir twice daily, 2.49 and 0.74 for darunavir-ritonavir once daily, 0.42 and 0.74 for atazanavir-ritonavir, 0.57 and 0.95 for lopinavir-ritonavir, and 0.19 and 0.84 for tipranavir-ritonavir, respectively. Therefore, the antiviral effect of ritonavir was less than that of the concomitant protease inhibitors but, importantly, mostly with darunavir. Thus, further
in vitro
and
in vivo
studies of the RTV antiviral effect are warranted.
Targeting Methicillin-Resistant Staphylococcus aureus with Short Salt-Resistant Synthetic Peptides
Authors: Mohamed Mohamed F. , Hamed Maha I. , Panitch Alyssa , Seleem Mohamed N.
Published: May 2014

The seriousness of microbial resistance combined with the lack of new antimicrobials has increased interest in the development of antimicrobial peptides (AMPs) as novel therapeutics. In this study, we evaluated the antimicrobial activities of two short synthetic peptides, namely, RRIKA and RR. These peptides exhibited potent antimicrobial activity against
Staphylococcus aureus
, and their antimicrobial effects were significantly enhanced by addition of three amino acids in the C terminus, which consequently increased the amphipathicity, hydrophobicity, and net charge. Moreover, RRIKA and RR demonstrated a significant and rapid bactericidal effect against clinical and drug-resistant
Staphylococcus
isolates, including methicillin-resistant
Staphylococcus aureus
(MRSA), vancomycin-intermediate
S. aureus
(VISA), vancomycin-resistant
S. aureus
(VRSA), linezolid-resistant
S. aureus
, and methicillin-resistant
Staphylococcus epidermidis
. In contrast to many natural AMPs, RRIKA and RR retained their activity in the presence of physiological concentrations of NaCl and MgCl
2
. Both RRIKA and RR enhanced the killing of lysostaphin more than 1,000-fold and eradicated MRSA and VRSA isolates within 20 min. Furthermore, the peptides presented were superior in reducing adherent biofilms of
S. aureus
and
S. epidermidis
compared to results with conventional antibiotics. Our findings indicate that the staphylocidal effects of our peptides were through permeabilization of the bacterial membrane, leading to leakage of cytoplasmic contents and cell death. Furthermore, peptides were not toxic to HeLa cells at 4- to 8-fold their antimicrobial concentrations. The potent and salt-insensitive antimicrobial activities of these peptides present an attractive therapeutic candidate for treatment of multidrug-resistant
S. aureus
infections.
Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 2. Colistin
Authors: Gontijo Aline Vidal Lacerda , Grégoire Nicolas , Lamarche Isabelle , Gobin Patrice , Couet William , Marchand Sandrine
Published: May 2014

The purpose of this study was to investigate the pharmacokinetic properties of colistin following intrapulmonary administration of colistin sulfate in rats. Colistin was infused or delivered in nebulized form at a dose of 0.35 mg/kg of body weight in rats, and plasma drug concentrations were measured for 4 h after administration. Bronchoalveolar lavages (BAL) were also conducted at 0.5, 2, and 4 h after intravenous (i.v.) administration and administration via nebulized drug to estimate epithelial lining fluid (ELF) drug concentrations. Unbound colistin plasma concentrations at distribution equilibrium (2 h postdosing) were almost identical after i.v. infusion and nebulized drug inhalation. ELF drug concentrations were undetectable in BAL samples after i.v. administration, but they were about 1,800 times higher than unbound plasma drug levels at 2 h and 4 h after administration of the nebulized drug. Simultaneous pharmacokinetic modeling of plasma and ELF drug concentrations was performed with a model characterized by a fixed physiological volume of ELF (
V
ELF
), a passive diffusion clearance (
Q
ELF
) between plasma and ELF, and a nonlinear influx transfer from ELF to the central compartment, which was assessed by reducing the nebulized dose of colistin by 10-fold (0.035 mg kg
−1
). The

k
m

was estimated to be 133 μg ml
−1
, and the
V
max, in
-to-

K
m

ratio was equal to 2.5 × 10
−3
liter h
−1
kg
−1
, which was 37 times higher than the
Q
ELF
(6.7 × 10
−5
liter h
−1
kg
−1
). This study showed that with the higher ELF drug concentrations after administration via nebulized aerosol than after intravenous administration, for antibiotics with low permeability such as colistin, nebulization offers a real potential over intravenous administration for the treatment of pulmonary infections.
Mycobacterium arupense Flexor Tenosynovitis: Case Report and Review of Antimicrobial Susceptibility Profiles for 40 Clinical Isolates
Authors: Beam Elena , Vasoo Shawn , Simner Patricia J. , Rizzo Marco , Mason Erin L. , Walker Randall C. , Deml Sharon M. , Brown-Elliott Barbara A. , Wallace Richard J. , Wengenack Nancy L. , Sia Irene G.
Published: May 2014

We describe a case of chronic tenosynovitis in the hand of a 58-year-old cattle farmer. Surgical biopsy specimens grew
Mycobacterium arupense
. The patient responded to surgery and antimicrobial therapy based on
in vitro
susceptibility testing. The antimicrobial susceptibility profiles of the isolate from this patient and 39 additional clinical isolates are presented.
Use of Imipenem To Detect KPC, NDM, OXA, IMP, and VIM Carbapenemase Activity from Gram-Negative Rods in 75 Minutes Using Liquid Chromatography-Tandem Mass Spectrometry
Authors: Kulkarni M. V. , Zurita A. N. , Pyka J. S. , Murray T. S. , Hodsdon M. E. , Peaper D. R.
Published: May 2014

Resistance to extended-spectrum β-lactam antibiotics has led to a greater reliance upon carbapenems, but the expression of carbapenemases threatens to limit the utility of these drugs. Current methods to detect carbapenemase activity are suboptimal, requiring prolonged incubations during which ineffective therapy may be prescribed. We previously described a sensitive and specific assay for the detection of carbapenemase activity using ertapenem and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we assessed 402 Gram-negative rods, including both
Enterobacteriaceae
and non-
Enterobacteriaceae
expressing IMP, VIM, KPC, NDM, and/or OXA carbapenemases, by using imipenem, meropenem, and ertapenem with LC-MS/MS assays. LC-MS/MS methods for the detection of intact and hydrolyzed carbapenems from an enrichment broth were developed. No ion suppression was observed, and the limits of detection for all three drugs were below 0.04 μg/ml. The sensitivity and specificity of meropenem and ertapenem for carbapenemase activity among non-
Enterobacteriaceae
were low, but imipenem demonstrated a sensitivity and specificity of 96% and 95%, respectively, among all Gram-negative rods (GNR) tested, including both
Enterobacteriaceae
and non-
Enterobacteriaceae
. LC-MS/MS allows for the analysis of more complex matrices, and this LC-MS/MS assay could easily be adapted for use with primary specimens requiring growth enrichment.
Whole-Genome-Based Mycobacterium tuberculosis Surveillance: a Standardized, Portable, and Expandable Approach
Authors: Kohl Thomas A. , Diel Roland , Harmsen Dag , Rothgänger Jörg , Walter Karen Meywald , Merker Matthias , Weniger Thomas , Niemann Stefan
Published: May 2014

Whole-genome sequencing (WGS) allows for effective tracing of
Mycobacterium tuberculosis
complex (MTBC) (tuberculosis pathogens) transmission. However, it is difficult to standardize and, therefore, is not yet employed for interlaboratory prospective surveillance. To allow its widespread application, solutions for data standardization and storage in an easily expandable database are urgently needed. To address this question, we developed a core genome multilocus sequence typing (cgMLST) scheme for clinical MTBC isolates using the Ridom SeqSphere
+
software, which transfers the genome-wide single nucleotide polymorphism (SNP) diversity into an allele numbering system that is standardized, portable, and not computationally intensive. To test its performance, we performed WGS analysis of 26 isolates with identical IS
6110
DNA fingerprints and spoligotyping patterns from a longitudinal outbreak in the federal state of Hamburg, Germany (notified between 2001 and 2010). The cgMLST approach (3,041 genes) discriminated the 26 strains with a resolution comparable to that of SNP-based WGS typing (one major cluster of 22 identical or closely related and four outlier isolates with at least 97 distinct SNPs or 63 allelic variants). Resulting tree topologies are highly congruent and grouped the isolates in both cases analogously. Our data show that SNP- and cgMLST-based WGS analyses facilitate high-resolution discrimination of longitudinal MTBC outbreaks. cgMLST allows for a meaningful epidemiological interpretation of the WGS genotyping data. It enables standardized WGS genotyping for epidemiological investigations, e.g., on the regional public health office level, and the creation of web-accessible databases for global TB surveillance with an integrated early warning system.
Lowenstein-Jensen Selective Medium for Reducing Contamination in Mycobacterium tuberculosis Culture
Authors: Kassaza Kennedy , Orikiriza Patrick , Llosa Augusto , Bazira Joel , Nyehangane Dan , Page Anne-Laure , Boum Yap
Published: May 2014

We compared
Mycobacterium tuberculosis
sputum culture recovery and contamination rates between Lowenstein-Jensen medium (LJ) containing the following decontaminants and LJ alone: (i) PANTA (
n
= 299), (ii) Selectatab-MB (
n
= 299), and (iii) penicillin G (
n
= 234). The contamination rate for LJ alone was approximately 31%, versus 5.0% for PANTA-containing, 2% for Selectatab-containing, and 9% for penicillin-containing media (
P
< 0.001).
M. tuberculosis
isolation rates were 9.8%, 17%, 18%, and 12% for standard LJ, PANTA, Selectatab, and penicillin cultures, respectively.
Real-Time Detection of HIV-2 by Reverse Transcription–Loop-Mediated Isothermal Amplification
Authors: Curtis Kelly A. , Niedzwiedz Philip L. , Youngpairoj Ae S. , Rudolph Donna L. , Owen S. Michele
Published: May 2014

Currently, there are no FDA-approved nucleic acid amplification tests (NAATs) for the detection or confirmation of HIV-2 infection. Here, we describe the development of a real-time assay for the detection of HIV-2 DNA and RNA using reverse transcription–loop-mediated isothermal amplification (RT-LAMP) and the ESEQuant tube scanner, a portable isothermal amplification/detection device.
Evaluation of the Bio-Rad Geenius HIV 1/2 Assay as an Alternative to the INNO-LIA HIV 1/2 Assay for Confirmation of HIV Infection
Authors: Mor Orna , Mileguir Fernando , Michaeli Michal , Levy Itzchak , Mendelson Ella
Published: May 2014

The Bio-Rad Geenius HIV 1/2 assay was evaluated as an alternative to the INNO-LIA HIV 1/2 assay for the confirmation of HIV infection in 198 serum samples reactive to 4th-generation HIV enzyme immunoassays (EIAs). The Geenius assay correctly identified 85% of the samples, compared to 75% identified by the INNO-LIA assay, reduced the number of indeterminate results, and shortened the overall turnaround time.
Clinical, Morphological, and Molecular Characterization of Penicilliumcanissp. nov., Isolated from a Dog with Osteomyelitis
Authors: Langlois Daniel K. , Sutton Deanna A. , Swenson Cheryl L. , Bailey Chris J. , Wiederhold Nathan P. , Nelson Nathan C. , Thompson Elizabeth H. , Wickes Brian L. , French Stephanie , Fu Jianmin , Vilar-Saavedra Paulo , Peterson Stephen W.
Published: May 2014

Infections caused byPenicilliumspecies are rare in dogs, and the prognosis in these cases is poor. An unknown species ofPenicilliumwas isolated from a bone lesion in a young dog with osteomyelitis of the right ilium. Extensive diagnostic evaluation did not reveal evidence of dissemination. Resolution of lameness and clinical stability of disease were achieved with intravenous phospholipid-complexed amphotericin B initially, followed by long-term combination therapy with terbinafine and ketoconazole. A detailed morphological and molecular characterization of the mold was undertaken. Sequence analysis of the internal transcribed spacer revealed the isolate to be closely related toPenicilliummenonorumandPenicilliumpimiteouiense. Additional sequence analysis of β-tubulin, calmodulin, minichromosome maintenance factor, DNA-dependent RNA polymerase, and pre-rRNA processing protein revealed the isolate to be a novel species; the namePenicilliumcanissp. nov. is proposed. Morphologically, smooth, ovoid conidia, a greenish gray colony color, slow growth on all media, and a failure to form ascomata distinguish this species from closely relatedPenicilliumspecies.
Incidence of Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates That Test Susceptible to Cephalosporins and Aztreonam by the Revised CLSI Breakpoints
Authors: McWilliams Carla S. , Condon Susan , Schwartz Rebecca M. , Ginocchio Christine C.
Published: May 2014

The incidence of aztreonam and cephalosporin susceptibility, determined using the revised CLSI breakpoints, for extended-spectrum-β-lactamase (ESBL)-producing
Escherichia coli
and
Klebsiella pneumoniae
isolates was evaluated. Our analysis showed that results for aztreonam and/or ≥1 cephalosporin were reported as susceptible or intermediate for 89.2% of ESBL-producing
E coli
isolates (569/638 isolates) and 67.7% of ESBL-producing
K. pneumoniae
isolates (155/229 isolates).
Promotion of a Subdominant CD8 T Cell Response during Murine Gammaherpesvirus 68 Infection in the Absence of CD4 T Cell Help
Authors: Freeman Michael L. , Roberts Alan D. , Burkum Claire E. , Woodland David L. , Blackman Marcia A.
Published: May 2014

CD8 and CD4 T cells are each critically important for immune control of murine gammaherpesvirus 68 (γHV68) infection. In immunocompetent mice, acute γHV68 infection results in lifelong latency, but in the absence of CD4 T cell help, mice succumb to viral recrudescence and disease. However, the requirements for CD4 T cell help in the generation and maintenance of antiviral CD8 T cell responses are incompletely understood, and it is unclear whether there are epitope-specific differences in the requirement of CD8 T cells for CD4 help. In this report, we characterized the CD8 T cell response to γHV68 in major histocompatibility complex (MHC) class II−/−mice, which lack CD4 T cells, or after antibody-mediated depletion of CD4 T cells. All antiviral CD8 T cells exhibited marked upregulation of surface expression of the inhibitory receptor programmed death-1 (PD-1), but surprisingly, while the immunodominant memory response appeared to be functionally impaired, helpless CD8 T cells of a subdominant specificity had increased numbers and enhanced functionality. Thus, we demonstrate differential requirements for CD4 help in the antiviral CD8 T cell response to a latent gammaherpesvirus.

IMPORTANCEγHV68 is a mouse pathogen closely related to the oncogenic human γHVs, which infect a majority of the world's population. Reactivation of these viruses from latency can lead to complications, disease, and even death. CD4 T cells are required for complete immune control of long-term infection, in part by providing key signals to dendritic cells that in turn instruct optimal antiviral CD8 T cell responses. We have investigated multiple virus-specific CD8 T cell responses during infection and identified a subdominant CD8 T cell response that is numerically and functionally enhanced in the absence of CD4 T cell help. This occurs in spite of high surface expression of an inhibitory receptor and in contrast to the immunodominant response, which is impaired. Our data suggest that signals from CD4 T cells are important in maintaining the CD8 T cell hierarchy during γHV infections.