bluuebunny/crossref_metadata_2025 huggingface dataset:
Habitat management as a generalized tool to boost European rabbit Oryctolagus cuniculus populations in the Iberian Peninsula: a cost‐effectiveness analysis
Authors: Ferreira Catarina , Touza Julia , Rouco Carlos , Díaz‐Ruiz Francisco , Fernandez‐de‐Simon Javier , Ríos‐Saldaña Carlos Antonio , Ferreras Pablo , Villafuerte Rafael , Delibes‐Mateos Miguel
Published: April 2013

The European rabbit Oryctolagus cuniculus was designated as a protected species in Spain and Portugal following sharp declines in many populations. The ongoing decline highlights the need to implement cost‐effective management strategies for this staple prey and important small game species of Iberian Mediterranean ecosystems.

Habitat management is one strategy in general use, though little is known about its true influence on rabbit populations. The main goal of this study was to assess the frequency of use and cost‐effectiveness of habitat management techniques for European rabbit populations in the Iberian Peninsula. We conducted a thorough literature review and used this information to: (i) estimate the frequency of use of habitat management techniques; (ii) evaluate the relative and absolute effectiveness of habitat management; and (iii) assess the economic implications of its application.

At least one habitat management technique was used on over 60% of hunting estates. The relative effectiveness (measured as the % population change before and after management) of habitat management techniques is high, although we found no relationship between high relative effectiveness and rabbit densities considered biologically and/or economically meaningful (e.g. densities able to support a breeding population of endangered predators or medium to high rabbit harvest yields). We did not find any clear relationship between the cost and the effectiveness of the habitat management techniques applied, as the most costly techniques were not the most successful ones.

We conclude that rabbit management strategies in the Iberian Peninsula should include improved and upscaled protocols for habitat management, in order to mitigate threats and promote the recovery of rabbit populations.
Quantifying noble gas contamination during terrestrial alteration in Martian meteorites from Antarctica
Authors: Schwenzer S. P. , Greenwood R. C. , Kelley S. P. , Ott U. , Tindle A. G. , Haubold R. , Herrmann S. , Gibson J. M. , Anand M. , Hammond S. , Franchi I. A.
Published: April 2013

We investigated exterior and interior subsamples from the Martian shergottite meteorites Allan Hills (ALH) A77005 and Roberts Massif (RBT) 04261 for secondary minerals, oxygen isotopes, Ar‐Ar, and noble gas signatures. Electron microprobe investigations revealed that RBT 04261 does not contain any visible alteration even in its most exterior fractures, whereas fracture fillings in ALHA77005 penetrate into the meteorite up to 300 μm, beyond which the fractures are devoid of secondary minerals. Light noble gases seem to be almost unaffected by terrestrially induced alteration in both meteorites. Thus, a shock metamorphic overprint of 30–35 GPa can be deduced from the helium measurements in RBT 04261. Oxygen isotopes also seem unaffected by terrestrially weathering and variations can easily be reconciled with the differences in modal mineralogy of the exterior and interior subsamples. The measurements on irradiated samples (Ar‐Ar) showed a clear Martian atmospheric contribution in ALHA77005, but this is less apparent in our sample of RBT 04261. Exterior and interior subsamples show slight differences in apparent ages, but the overall results are very similar between the two. In contrast, krypton and xenon are severely affected by terrestrial contamination, demonstrating the ubiquitous presence of elementally fractionated air in RBT 04261. Although seemingly contradictory, our results indicate that RBT 04261 was more affected by contamination than ALHA77005. We conclude that irrespective of on which planet the alteration occurred, exposure of Martian rocks to atmosphere (or brine) introduces noble gases with signatures elementally fractionated relative to the respective atmospheric composition into the rock, and relationships of that process with oxygen isotopes or mineralogical observations are not straightforward.
Effective treatment of erythrasma‐associated inflammation and pruritus with isoconazole nitrate and diflucortolone valerate combination therapy
Authors: Piergiorgio Malagoli
Published: April 2013

A warm and moist environment is a common risk factor for erythrasma, a condition characterized by pruritic, scaly and erythematous tan patches on the skin. Here we report on a 13‐year‐old athletic student presenting with pruritus and mild burning on her left medial thigh, and subsequently diagnosed with erythrasma. The patient was successfully treated with a 5‐day regimen of Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%.
Isoconazole nitrate: a unique broad‐spectrum antimicrobial azole effective in the treatment of dermatomycoses, both as monotherapy and in combination with corticosteroids
Authors: Veraldi Stefano
Published: April 2013

Fungal skin infections, or dermatomycoses, are associated with a broad range of pathogens. Involvement of gram‐positive bacteria is often suspected in dermatomycoses. Inflammation plays an important role in dermatomycoses, displaying a close association between frequent inflammation and reduced skin‐related quality of life. Isoconazole nitrate (ISN) is a broad‐spectrum antimicrobial agent with a highly effective antimycotic and gram‐positive antibacterial activity, a rapid rate of absorption and low systemic exposure potential. ISN is effective against pathogens involved in dermatomycoses, with minimum inhibitory concentrations well below the concentration of ISN in skin and hair follicles. The combination of the corticosteroid diflucortolone valerate with ISN (Travocort®) increases the local bioavailability of ISN. Compared with ISN monotherapy, Travocort has a faster onset of antimycotic action, faster relief of itch and other inflammatory symptoms, improved overall therapeutic benefits and earlier mycological cure rate. Travocort is effective in the treatment of inflammatory mycotic infections, and also in the eradication of accompanied gram‐positive bacterial infections. The rapid improvement observed with Travocort treatment, combined with favourable safety and tolerability, results in higher patient satisfaction, and therefore, can be an effective tool to increase treatment adherence in patients with dermatomycoses accompanied by inflammatory signs and symptoms.
Misdiagnosed zoophile tinea faciei and tinea corporis effectively treated with isoconazole nitrate and diflucortolone valerate combination therapy
Authors: Czaika Viktor A.
Published: April 2013

There have been few published reports on the human transmission of Trichophyton mentagrophytes, a zoophilic fungus frequently occurring in pets. Here we report on 2 girls, living with a pet dwarf rabbit, who presented with inflammatory skin lesions positive for T. mentagrophytes and subsequently diagnosed as zoophile tinea faciei and tinea corporis. The patients were successfully treated with systemic terbinafine and 2‐week therapy with Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%.
Rapid relief of intertrigo‐associated pruritus due to Candida albicans with isoconazole nitrate and diflucortolone valerate combination therapy
Authors: Veraldi Stefano
Published: April 2013

A 43‐year‐old male, with intertrigo due to Candida albicans located at the inguinal folds and accompanied by severe pruritus, was treated with topical 1% isoconazole nitrate and 0.1% diflucortolone valerate (2 applications/day for 7 days). An improvement of pruritus was reported 2 days after the beginning of the treatment. Skin lesions improved after 3 days of treatment. Complete remission of both skin lesions and pruritus was observed at day 7. No side effects were observed.
Effective treatment of tinea corporis due to Trichophyton mentagrophytes with combined isoconazole nitrate and diflucortolone valerate therapy
Authors: Czaika Viktor A.
Published: April 2013

Trichophyton mentagrophytes is the dermatophyte species most commonly reported in cases of guinea pig‐associated dermatophytosis (or guinea pig fungus) a condition that more often affects children than adults. In this case, a 13‐year‐old girl with recent direct contact with guinea pigs presented with a previously undertreated inflammatory skin lesion on the left side of her upper body, which was positive both for Trichophyton mentagrophytes and Staphylococcus epidermidis. The condition was subsequently diagnosed as tinea corporis due to Trichophyton mentagrophytes with concomitant bacterial infection and effectively treated with 2 weeks of twice‐daily application of Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%. Visible improvement in the lesion was apparent after only 1 week of treatment.
Candidaemia in polish hospitals – a multicentre survey
Authors: Nawrot Urszula , Pajączkowska Magdalena , Fleischer Małgorzata , Przondo‐Mordarska Hanna , Samet Alfred , Piasecka‐Pazik Dorota , Komarnicka Jolanta , Sulik‐Tyszka Beata , Swoboda‐Kopeć Ewa , Cieślik Justyna , Mikucka Agnieszka , Gospodarek Eugenia , Ozorowski Tomasz , Mól Anna , Tryniszewska Elżbieta , Kłosowska Wioletta , Krawczyk Małgorzata , Golec Krzysztof , Szymaniak Ludmiła , Giedrys‐Kalemba Stefania , Bilska Iwona , Prawda‐Zołotar Jolanta , Juszczyk‐Grudzińska Małgorzata , Wróblewska Małgorzata , Burdynowski Krzysztof
Published: April 2013

Significant changes in the frequency of candidaemia and the distribution of causative species have been noted worldwide in the last two decades. In this study, we present the results of the first multicentre survey of fungaemia in Polish hospitals. A total of 302 candidaemia episodes in 294 patients were identified in 20 hospitals during a 2‐year period. The highest number of infections was found in intensive care (30.8%) and surgical (29.5%) units, followed by haematological (15.9%), ‘others’ (19.2%) and neonatological (4.6%) units. Candida albicans was isolated from 50.96% of episodes; its prevalence was higher in intensive care unit and neonatology (61.22% and 73.33%, respectively), and significantly lower in haematology (22%; P < 0.001). The frequency of C. krusei and C. tropicalis was significantly higher (24% and 18%) in haematology (P < 0.02); whereas, the distribution of C. glabrata (14.1%) and C. parapsilosis (13.1%) did not possess statistically significant differences between compared departments. Obtained data indicates that species distribution of Candida blood isolates in Polish hospitals reflects worldwide trends, particularly a decrease in the prevalence of infections due to C. albicans.
What Can We Learn from a University that Rewards Faculty Practice?
Authors: Docherty Jayne Seminare
Published: April 2013

What conditions, including standards for promotion and tenure, should we be cultivating at universities if we want scholar practitioners (or pracademics) in conflict‐related fields to thrive in academic settings? This article examines the Center for Justice and Peacebuilding at Eastern Mennonite University as an example of “positive deviance” — a university and an academic program that wholeheartedly support faculty members who engage in extensive practice, including long‐term involvement with peacebuilding processes. Three conditions — location, culture, and the application of peacebuilding strategies within the university — have given rise to and continue to support this system even as the university embraces a commitment to increasing scholarly productivity by faculty members.
Fine‐scale spatial genetic structure of the black truffle (Tuber melanosporum) investigated with neutral microsatellites and functional mating type genes
Authors: Murat Claude , Rubini Andrea , Riccioni Claudia , De la Varga Herminia , Akroume Emila , Belfiori Beatrice , Guaragno Marco , Le Tacon François , Robin Christophe , Halkett Fabien , Martin Francis , Paolocci Francesco
Published: April 2013

The genetic structure of ectomycorrhizal (ECM) fungal populations results from both vegetative and sexual propagation. In this study, we have analysed the spatial genetic structure of Tuber melanosporum populations, a heterothallic ascomycete that produces edible fruit bodies.

Ectomycorrhizas from oaks and hazels from two orchards were mapped and genotyped using simple sequence repeat markers and the mating type locus. The distribution of the two T. melanosporum mating types was also monitored in the soil. In one orchard, the genetic profiles of the ascocarps were compared with those of the underlying mycorrhizas.

A pronounced spatial genetic structure was found. The maximum genet sizes were 2.35 and 4.70 m in the two orchards, with most manifesting a size < 1 m. Few genets persisted throughout two seasons. A nonrandom distribution pattern of the T. melanosporum was observed, resulting in field patches colonized by genets that shared the same mating types.

Our findings suggest that competition occurs between genets and provide basic information on T. melanosporum propagation patterns that are relevant for the management of productive truffle orchards.
McArdle's disease (glycogen storage disease typeV) and anesthesia – a case report and review of the literature
Authors: Bollig Georg
Published: April 2013

McArdles disease (glycogen storage disease type v) is a rare condition in which energy‐metabolism in the muscle is hampered. A case report is presented and the possible risk for perioperative complications including malignant hyperthermia is discussed. A checklist for the anesthesiological management of patients withMcArdles disease is provided. A short overview of anesthesiological challenges and perioperative complications of other glycogen storage diseases is given.
Low‐dose ketamine as a potential adjuvant therapy for painful vaso‐occlusive crises in sickle cell disease
Authors: Neri Caitlin M. , Pestieau Sophie R. , Darbari Deepika S.
Published: April 2013

The hallmark of sickle cell disease (SCD) is the acute painful vaso‐occlusive crisis (VOC). Among SCD patients, vaso‐occlusive pain episodes vary in frequency and severity. Some patients rarely have painful crises, while others are admitted to the hospital multiple times in a year for parenteral analgesics. Opioids are the mainstay of therapy for SCD‐related pain. However, a subset of patients report continued pain despite escalating doses of opioids. Tolerance and opioid‐induced hyperalgesia (OIH) have been considered as possible explanations for this phenomenon. The activation of the N‐methyl‐d‐aspartate (NMDA) receptor has been implicated in both tolerance and OIH. As a NMDA receptor agonist, ketamine has been shown to modulate opioid tolerance and OIH in animal models and clinical settings. Low‐dose ketamine, by virtue of its NMDA receptor agonist activity, could be a useful adjuvant to opioid therapy in patients with refractory SCD‐related pain. Based on limited studies of adjuvant ketamine use for pain management, low‐dose ketamine continuous infusion appears safe. Further clinical investigations are warranted to fully support the use of low‐dose ketamine infusion in patients with SCD‐related pain.
Combined Bundle Block Adjustment with Spaceborne Linear Array and Airborne Frame Array Imagery
Authors: Zhang Yongjun , Lin Liwen , Zheng Maoteng , Xiong Jinxin
Published: April 2013

The integration of multi‐source earth observation data has become one of the most important developments in photogrammetry. A combined adjustment with linear array and frame array imagery (CALFI) is established in this paper. The mathematical model of CALFI is based on the conventional single‐source bundle adjustment. A revised recursive partitioning technique is utilised to solve the large normal matrix of CALFI; the orientation parameters of the linear array imagery are arranged at the border of the reduced normal matrix to save both memory and computation time. The experimental results on simulated data show that both the accuracy and the condition index of the CALFI model are superior to the conventional bundle adjustment model with either linear array or frame array imagery separately due to the higher redundancy.
Ethylene – and oxygen signalling – drive plant survival during flooding
Authors: Voesenek L. A. C. J. , Sasidharan R.
Published: April 2013

Flooding is a widely occurring environmental stress both for natural and cultivated plant species. The primary problems associated with flooding arise due to restricted gas diffusion underwater. This hampers gas exchange needed for the critical processes of photosynthesis and respiration. Plant acclimation to flooding includes the adaptation of a suite of traits that helps alleviate or avoid these stressful conditions and improves or restores exchange of O2 and CO2. The manifestation of these traits is, however, reliant on the timely perception of signals that convey the underwater status. Flooding‐associated reduced gas diffusion imposes a drastic change in the internal gas composition within submerged plant organs. One of the earliest changes is an increase in the levels of the gaseous plant hormone ethylene. Depending on the species, organ, flooding conditions and time of the day, plants will also subsequently experience a reduction in oxygen levels. This review provides a comprehensive overview on the roles of ethylene and oxygen as critical signals of flooding stress. It includes a discussion of the dynamics of these gases in plants when underwater, their interaction, current knowledge of their perception mechanisms and the resulting downstream changes that mediate important acclimative processes that allow endurance and survival under flooded conditions.
Impact of early and late winter icing events on sub‐arctic dwarf shrubs
Authors: Preece C. , Phoenix G. K.
Published: April 2013

Polar regions are predicted to undergo large increases in winter temperature and an increased frequency of freeze–thaw cycles, which can cause ice layers in the snow pack and ice encasement of vegetation. Early or late winter timing of ice encasement could, however, modify the extent of damage caused to plants. To determine impacts of the date of ice encasement, a novel field experiment was established in sub‐arctic Sweden, with icing events simulated in January and March 2008 and 2009. In the subsequent summers, reproduction, phenology, growth and mortality, as well as physiological indicators of leaf damage were measured in the three dominant dwarf shrubs: Vaccinium uliginosum, Vaccinium vitis‐idaea and Empetrum nigrum. It was hypothesised that January icing would be more damaging compared to March icing due to the longer duration of ice encasement. Following 2 years of icing, E. nigrum berry production was 83% lower in January‐iced plots compared to controls, and V. vitis‐idaea electrolyte leakage was increased by 69%. Conversely, electrolyte leakage of E. nigrum was 25% lower and leaf emergence of V. vitis‐idaea commenced 11 days earlier in March‐iced plots compared to control plots in 2009. There was no effect of icing on any of the other parameters measured, indicating that overall these study species have moderate to high tolerance to ice encasement. Even much longer exposure under the January icing treatment does not clearly increase damage.
Differential response of antioxidative systems of maize (Zea mays L.) roots cell walls to osmotic and heavy metal stress
Authors: Vuletić M. , Hadži‐Tašković Šukalović V. , Marković K. , Kravić N. , Vučinić Ž. , Maksimović V.
Published: April 2013

An analysis of peroxidase and ascorbate oxidase activity, phenolic content and antioxidant capacity of isolated maize root cell walls was performed in controls and plants stressed with polyethylene glycol (PEG) or heavy metals, zinc or copper. Peroxidase activity (oxidative and peroxidative) was more pronounced in the ionic than in the covalent cell wall fraction. PEG induced an increase and Zn2+ a decrease of both ionically bound peroxidase activities. In the covalent fraction, Cu2+ decreased oxidative and increased peroxidative activity of peroxidase. Isoelectric focusing of ionically bound proteins and activity staining for peroxidase demonstrated increased intensities and appearance of new acidic isoforms, especially in Zn2+ and PEG treatments. Most pronounced basic isoforms (pI ~ 7.5) in controls, decreased in intensity or completely disappeared in stressed plants. Ascorbate oxidase activity was significantly increased by PEG and decreased by Zn2+ treatments, and highly correlated with peroxidase activity. Antioxidant capacity and total phenolics content increased in heavy metal‐treated and decreased in PEG‐treated plants. Analysis of individual phenolic components revealed p‐coumaric and ferulic acids, as the most abundant, as well as ferulic acid dimers, trimers and tetramers in the cell walls; their quantity increased under stress conditions. Results presented demonstrate the existence of diverse mechanisms of plant response to different stresses.
Cell Phone Exposures and Hearing Loss in Children in the Danish National Birth Cohort
Authors: Sudan Madhuri , Kheifets Leeka , Arah Onyebuchi A. , Olsen Jorn
Published: April 2013

Background

Children today are exposed to cell phones early in life, and may be the most vulnerable if exposure is harmful to health. We investigated the association between cell phone use and hearing loss in children.

Methods

The Danish National Birth Cohort (DNBC) enrolled pregnant women between 1996 and 2002. Detailed interviews were conducted during gestation, and when the children were 6 months, 18 months and 7 years of age. We used multivariable‐adjusted logistic regression, marginal structural models (MSM) with inverse‐probability weighting, and doubly robust estimation (DRE) to relate hearing loss at age 18 months to cell phone use at age 7 years, and to investigate cell phone use reported at age 7 in relation to hearing loss at age 7.

Results

Our analyses included data from 52 680 children. We observed weak associations between cell phone use and hearing loss at age 7, with odds ratios and 95% confidence intervals from the traditional logistic regression, MSM and DRE models being 1.21 [95% confidence interval [CI] 0.99, 1.46], 1.23 [95% CI 1.01, 1.49] and 1.22 [95% CI 1.00, 1.49], respectively.

Conclusions

Our findings could have been affected by various biases and are not sufficient to conclude that cell phone exposures have an effect on hearing. This is the first large‐scale epidemiologic study to investigate this potentially important association among children, and replication of these findings is needed.
Smoking during Pregnancy and Risk of Autism Spectrum Disorder in a Finnish National Birth Cohort
Authors: Tran Phuong Lien , Lehti Venla , Lampi Katja M. , Helenius Hans , Suominen Auli , Gissler Mika , Brown Alan S. , Sourander Andre
Published: April 2013

Background

Results of previous population‐based studies examining associations between smoking during pregnancy and autism spectrum disorders (ASD) are contradictory. Furthermore, there is a lack of population‐based studies examining the relationship between smoking during pregnancy and the main diagnostic subtypes of ASD.

Methods

We conducted a population‐based nested case–control study based on the Finnish Prenatal Study of Autism (FIPS‐A) among liveborn infants delivered in Finland between 1987 and 2005. Data on maternal smoking during pregnancy were available from the Finnish Medical Birth Register (FMBR) since October 1990. Data on ASD in the offspring were obtained from the Finnish Hospital Discharge Register (FHDR).

Results

Among the three subtypes of ASD, maternal smoking during the whole pregnancy was associated with an increased risk of pervasive developmental disorder (PDD) (odds ratio 1.2, 95% confidence interval 1.0, 1.5). The increase in odds persisted after controlling for maternal age, mother's socio‐economic and psychiatric status, and infant's weight for gestational age. However, smoking exposure limited to the first trimester was not associated with PDD or any of the other ASD subtypes.

Conclusions

Maternal smoking is related to a modest increase in risk of PDD, while no associations were observed for childhood autism and Asperger's syndrome.
Maternal Smoking During Pregnancy and Failure of the Georgia First Grade Criterion‐Referenced Competency Test
Authors: Feng Jia , Kramer Michael R. , Dever Bridget V. , Dunlop Anne L. , Williams Bryan , Jain Lucky
Published: April 2013

Background

Maternal smoking during pregnancy (MSDP) has been reported to be associated with impaired measures of cognitive function, but it remains unclear whether exposure to MSDP has an impact upon offspring school performance. We examined the association between MSDP and failure of the Criterion‐Referenced Competency Tests (CRCT) among Georgia first grade students.

Methods

A retrospective cohort was created by deterministically linking 331 531 children born in Georgia from 1998 to 2002 (inclusive) to their individual CRCT education records from 2005 to 2009. We evaluated the association between MSDP (yes/no) and failure of the CRCT Reading, English/Language Arts (ELA), and Mathematics tests, with adjustment for maternal and child sociodemographic characteristics and birth outcomes. Log‐binomial models estimated the risk ratios and 95% confidence intervals. Conditional models were fitted to paired sibling data.

Results

MSDP was associated with CRCT failure with an adjusted risk ratios for Reading: 1.16 [95% CI 1.12, 1.21]; ELA: 1.12 [95%CI 1.10, 1.15]; and Mathematics: 1.13 [95%CI 1.10, 1.16]. The association remained significant in paired sibling analyses.

Conclusions

MSDP may have independent long‐term effects on offspring school performance, which does not appear to be through smoking‐related adverse birth outcomes.
Direct and Proxy Recall of Childhood Socio‐Economic Position and Health
Authors: Straughen Jennifer K. , Caldwell Cleopatra H. , Osypuk Theresa L. , Helmkamp Laura , Misra Dawn P.
Published: April 2013

Background

The utility of proxy reporting within the life course framework has not been adequately assessed; therefore we sought to assess the magnitude and type of agreement that exists between index and proxy reports for bodyweight, health, and socio‐economic position (SEP) in childhood.

Methods

Participants were enrolled as part of an ongoing study of preterm birth in African American women in Metro Detroit. Post‐partum women and their mothers (n = 333 pairs) provided retrospective reports about the woman's childhood bodyweight, health, and SEP. Agreement was assessed using kappa, weighted kappa (κ), and intraclass correlation coefficients (ICC). Log‐linear models were used to describe the pattern of agreement for ordinal data.

Results

Birthweight and weight at age 18 was reported with a high level of agreement (ICC = 0.86 and 0.71, respectively). Kappa indicated moderate agreement for early and late childhood/adolescent weight. Log‐linear models suggested that there was diagonal agreement plus linear by linear association for early childhood weight and linear by linear association in late childhood/adolescence. Reports of childhood medical problems and hospitalisations had only moderate agreement. Agreement for SEP in both early (κ = 0.14) and late childhood/adolescence (κ = 0.20) was poor. Log‐linear models suggest a linear by linear association, indicating a positive association between the responses.

Conclusions

Results suggest that proxy reports may be utilised in conjunction with an index report to provide an estimate of the accuracy of report or to more fully capture experiences over the life course. This may be particularly useful when multiple developmental periods are examined.
Pregnancy Recruitment for Population Research: the National Children's Study Vanguard Experience in Wayne County, Michigan
Authors: Kerver Jean M. , Elliott Michael R. , Norman Gwendolyn S. , Sokol Robert J. , Keating Daniel P. , Copeland Glenn E. , Johnson Christine C. , Cislo Kendall K. , Alcser Kirsten H. , Kruger‐Ndiaye Shonda R. , Pennell Beth‐Ellen , Mehta Shobha , Joseph Christine L. M. , Paneth Nigel ,   MANCS Executive Committee
Published: April 2013

Background

To obtain a probability sample of pregnancies, the National Children's Study conducted door‐to‐door recruitment in randomly selected neighbourhoods in randomly selected counties in 2009–10. In 2011, an experiment was conducted in 10 US counties, in which the two‐stage geographic sample was maintained, but participants were recruited in prenatal care provider offices. We describe our experience recruiting pregnant women this way in Wayne County, Michigan, a county where geographically eligible women attended 147 prenatal care settings, and comprised just 2% of total county pregnancies.

Methods

After screening for address eligibility in prenatal care offices, we used a three‐part recruitment process: (1) providers obtained permission for us to contact eligible patients, (2) clinical research staff described the study to women in clinical settings, and (3) survey research staff visited the home to consent and interview eligible women.

Results

We screened 34 065 addresses in 67 provider settings to find 215 eligible women. Providers obtained permission for research contact from 81.4% of eligible women, of whom 92.5% agreed to a home visit. All home‐visited women consented, giving a net enrolment of 75%. From birth certificates, we estimate that 30% of eligible county pregnancies were enrolled, reaching 40–50% in the final recruitment months.

Conclusions

We recruited a high fraction of pregnancies identified in a broad cross‐section of provider offices. Nonetheless, because of time and resource constraints, we could enrol only a fraction of geographically eligible pregnancies. Our experience suggests that the probability sampling of pregnancies for research could be more efficiently achieved through sampling of providers rather than households.
Is Sweden Being Torn Apart? Privatization and Old and New Patterns of Welfare State Support
Authors: Edlund Jonas , Johansson Sevä Ingemar
Published: April 2013

This article examines the potential impact of institutional change on popular welfare support. The encompassing welfare state of Sweden provides an interesting case where the privatization of social service delivery has been widespread over the last decades. We use survey data from five rounds of the Swedish Welfare State Survey (1992, 1997, 2002, 2006 and 2010) in order to study how public preferences for the financing and organization of welfare services have changed over time. Based on a theory describing an ideal‐typical pattern of public support for an encompassing welfare model, we derive three types of public preferences: support for a pure state model, a pure market model and a mixed model (welfare services are funded by taxes but provided by private firms). We begin by tracking the development of these ideal‐typical attitude patterns between 1992 and 2010. We then investigate how preference patterns vary across municipalities displaying different degrees of privatization of social service delivery. Our results show that welfare support among Swedes over the last decades is better characterized as dynamic rather than stable. Swedes seem to take an overall more ideologically based position on the role of the welfare state over time. The share of respondents expressing such ideologically based preferences has increased from 54 per cent in 1992 to 78 per cent in 2010. This change is principally manifested in increased support for the state and mixed models. This trend seems to be parallel to the increasing share of private welfare service providers over the last decade. We also find a link between the municipal degree of privatization and support for our three ideal‐typical welfare models. Public support for a mixed welfare model and, to some extent, a market model, is comparatively stronger in municipalities where welfare services to a large extent are carried out by private actors. Conversely, data shows that public support for the traditional Swedish state model is more widespread in municipalities having a low degree of welfare services privatization. Lastly, we discuss some theoretical implications of our findings.
Achieving Democratic Leadership: A Data‐Mined Prescription
Authors: Jurek Steven J. , Scime Anthony
Published: April 2013

Objective

To understand what kind of individuals lead particular regimes, this study examines the most influential people in politics, the executives, to uncover the relationship between their characteristics and the type of regime they govern.

Methods

This article employs data mining with characteristics of executives worldwide against the state's Freedom House ranking.

Results

Through data mining, the results indicate that while there are still many important factors that coincide with democracy, the length of time in office and to a lesser extent the religious beliefs of executives and the likelihood of being classified as a democracy are heavily related.

Conclusion

This article concludes with a recommendation for supporting specific types of executives to increase the likelihood for successful democratization to minimize authoritarian rule.
Tungsten-based pillar deposition by helium ion microscope and beam-induced substrate damage
Authors: Kohama Kazuyuki , Iijima Tomohiko , Hayashida Misa , Ogawa Shinichi
Published: April 2013

The authors use a helium ion microscope (HIM) equipped with a tungsten hexacarbonyl gas injection system (GIS) to form tungsten-based pillars on carbon and silicon substrates by helium ion beam-induced deposition. Tungsten-based pillars with a width of ∼40 nm and height of ∼2 μm (aspect ratio of ∼50) are successfully fabricated using the HIM-GIS method. The pillars consist of face-centered cubic WC1−x and/or W2(C, O) grains. Columnar voids with a width of 1–15 nm form in the center of the pillars, suggesting that the pillars are continuously sputter-etched by the incident helium ion beam during deposition. In addition, the authors observe beam irradiation damage in the form of blistering of the Si substrate at the interface between the pillar and Si substrate. The columnar void width and Si blister height decreases as the volumetric growth rate of the pillars increases regardless of the deposition parameters. The authors consider that at least three phenomena compete during pillar formation, namely pillar deposition, sputter-etching, and Si blistering. Although there are numerous parameters involved in HIM-GIS deposition, it appears that the volumetric growth rate determines both the microstructure of the tungsten-based pillars and the degree of substrate damage.
Feasibility study on inverse four‐dimensional dose reconstruction using the continuous dose‐image of EPID
Authors: Yeo Inhwan Jason , Jung Jae Won , Yi Byong Yong , Kim Jong Oh
Published: April 2013

Purpose:

When an intensity‐modulated radiation beam is delivered to a moving target, the interplay effect between dynamic beam delivery and the target motion due to miss‐synchronization can cause unpredictable dose delivery. The portal dose image in electronic portal imaging device (EPID) represents radiation attenuated and scattered through target media. Thus, it may possess information about delivered radiation to the target. Using a continuous scan (cine) mode of EPID, which provides temporal dose images related to target and beam movements, the authors’ goal is to perform four‐dimensional (4D) dose reconstruction.

Methods:

To evaluate this hypothesis, first, the authors have derived and subsequently validated a fast method of dose reconstruction based on virtual beamlet calculations of dose responses using a test intensity‐modulated beam. This method was necessary for processing a large number of EPID images pertinent for four‐dimensional reconstruction. Second, cine mode acquisition after summation over all images was validated through comparison with integration mode acquisition on EPID (IAS3 and aS1000) for the test beam. This was to confirm the agreement of the cine mode with the integrated mode, specifically for the test beam, which is an accepted mode of image acquisition for dosimetry with EPID. Third, in‐phantom film and exit EPID dosimetry was performed on a moving platform using the same beam. Heterogeneous as well as homogeneous phantoms were used. The cine images were temporally sorted at 10% interval. The authors have performed dose reconstruction to the in‐phantom plane from the sorted cine images using the above validated method of dose reconstruction. The reconstructed dose from each cine image was summed to compose a total reconstructed dose from the test beam delivery, and was compared with film measurements.

Results:

The new method of dose reconstruction was validated showing greater than 95.3% pass rates of the gamma test with the criteria of dose difference of 3% and distance to agreement of 3 mm. The dose comparison of the reconstructed dose with the measured dose for the two phantoms showed pass rates higher than 96.4% given the same criteria.

Conclusions:

Feasibility of 4D dose reconstruction was successfully demonstrated in this study. The 4D dose reconstruction demonstrated in this study can be a promising dose validation method for radiation delivery on moving organs.
The Identification and Characterization of Breast Cancer CTCs Competent for Brain Metastasis
Authors: Zhang Lixin , Ridgway Lon D. , Wetzel Michael D. , Ngo Jason , Yin Wei , Kumar Disha , Goodman Jerry C. , Groves Morris D. , Marchetti Dario
Published: April 2013

EpCAM
−
CTCs isolated from breast cancer patients express markers needed to promote brain metastasis.
Community-Wide Isoniazid Preventive Therapy Drives Drug-Resistant Tuberculosis: A Model-Based Analysis
Authors: Mills Harriet L. , Cohen Ted , Colijn Caroline
Published: April 2013

Community-wide isoniazid preventive therapy may lead to long-term rises in resistance at the population level.
Offering Guidance for Translation
Authors: Au Patrick , Bailey Alexander M.
Published: April 2013

FDA recently released a draft-guidance on the preclinical assessment of investigational cellular and gene therapy products.
Wnt Modulating Agents Inhibit Human Cytomegalovirus Replication
Authors: Kapoor Arun , He Ran , Venkatadri Rajkumar , Forman Michael , Arav-Boger Ravit
Published: April 2013

Infection with human cytomegalovirus (HCMV) continues to be a threat for pregnant women and immunocompromised hosts. Although limited anti-HCMV therapies are available, development of new agents is desired. The Wnt signaling pathway plays a critical role in embryonic and cancer stem cell development and is targeted by gammaherpesviruses, Epstein-Barr virus (EBV), and Kaposi's sarcoma-associated herpesvirus (KSHV). HCMV infects stem cells, including neural progenitor cells, during embryogenesis. To investigate the role of Wnt in HCMV replication
in vitro
, we tested monensin, nigericin, and salinomycin, compounds that inhibit cancer stem cell growth by modulating the Wnt pathway. These compounds inhibited the replication of HCMV Towne and a clinical isolate. Inhibition occurred prior to DNA replication but persisted throughout the full replication cycle. There was a significant decrease in expression of IE2, UL44, and pp65 proteins. HCMV infection resulted in a significant and sustained decrease in expression of phosphorylated and total lipoprotein receptor-related protein 6 (pLRP6 and LRP6, respectively), Wnt 5a/b, and β-catenin and a modest decrease in Dvl2/3, while levels of the negative regulator axin 1 were increased. Nigericin decreased the expression of pLRP6, LRP6, axin 1, and Wnt 5a/b in noninfected and HCMV-infected cells. For all three compounds, a correlation was found between expression levels of Wnt 5a/b and axin 1 and HCMV inhibition. The decrease in Wnt 5a/b and axin 1 expression was more significant in HCMV-infected cells than noninfected cells. These data illustrate the complex effects of HCMV on the Wnt pathway and the fine balance between Wnt and HCMV, resulting in abrogation of HCMV replication. Additional studies are required to elucidate how HCMV targets Wnt for its benefit.
A Combined Pharmacodynamic Quantitative and Qualitative Model Reveals the Potent Activity of Daptomycin and Delafloxacin against Staphylococcus aureus Biofilms
Authors: Bauer Julia , Siala Wafi , Tulkens Paul M. , Van Bambeke Françoise
Published: April 2013

Biofilms are associated with persistence of
Staphylococcus aureus
infections and therapeutic failures. Our aim was to set up a pharmacodynamic model comparing antibiotic activities against biofilms and examining in parallel their effects on viability and biofilm mass. Biofilms of
S. aureus
ATCC 25923 (methicillin-sensitive
S. aureus
[MSSA]) or ATCC 33591 (methicillin-resistant
S. aureus
[MRSA]) were obtained by culture in 96-well plates for 6 h/24 h. Antibiotic activities were assessed after 24/48 h of exposure to concentrations ranging from 0.5 to 512 times the MIC. Biofilm mass and bacterial viability were quantified using crystal violet and the redox indicator resazurin. Biofilms stained with Live/Dead probes were observed by using confocal microscopy. Concentration-effect curves fitted sigmoidal regressions, with a 50% reduction toward both matrix and viability obtained at sub-MIC or low multiples of MICs against young biofilms for all antibiotics tested. Against mature biofilms, maximal efficacies and potencies were reduced, with none of the antibiotics being able to completely destroy the matrix. Delafloxacin and daptomycin were the most potent, reducing viability by more than 50% at clinically achievable concentrations against both strains, as well as reducing biofilm depth, as observed in confocal microscopy. Rifampin, tigecycline, and moxifloxacin were effective against mature MRSA biofilms, while oxacillin demonstrated activity against MSSA. Fusidic acid, vancomycin, and linezolid were less potent overall. Antibiotic activity depends on biofilm maturity and bacterial strain. The pharmacodynamic model developed allows ranking of antibiotics with respect to efficacy and potency at clinically achievable concentrations and highlights the potential utility of daptomycin and delafloxacin for the treatment of biofilm-related infections.
Model-Based Estimates of the Effects of Efavirenz on Bedaquiline Pharmacokinetics and Suggested Dose Adjustments for Patients Coinfected with HIV and Tuberculosis
Authors: Svensson Elin M. , Aweeka Francesca , Park Jeong-Gun , Marzan Florence , Dooley Kelly E. , Karlsson Mats O.
Published: April 2013

Safe, effective concomitant treatment regimens for tuberculosis (TB) and HIV infection are urgently needed. Bedaquiline (BDQ) is a promising new anti-TB drug, and efavirenz (EFV) is a commonly used antiretroviral. Due to EFV's induction of cytochrome P450 3A4, the metabolic enzyme responsible for BDQ biotransformation, the drugs are expected to interact. Based on data from a phase I, single-dose pharmacokinetic study, a nonlinear mixed-effects model characterizing BDQ pharmacokinetics and interaction with multiple-dose EFV was developed. BDQ pharmacokinetics were best described by a 3-compartment disposition model with absorption through a dynamic transit compartment model. Metabolites M2 and M3 were described by 2-compartment models with clearance of BDQ and M2, respectively, as input. Impact of induction was described as an instantaneous change in clearance 1 week after initialization of EFV treatment and estimated for all compounds. The model predicts average steady-state concentrations of BDQ and M2 to be reduced by 52% (relative standard error [RSE], 3.7%) with chronic coadministration. A range of models with alternative structural assumptions regarding onset of induction effect and fraction metabolized resulted in similar estimates of the typical reduction and did not offer a markedly better fit to data. Simulations to investigate alternative regimens mitigating the estimated interaction effect were performed. The results suggest that simple adjustments of the standard regimen during EFV coadministration can prevent reduced exposure to BDQ without increasing exposures to M2. However, exposure to M3 would increase. Evaluation in clinical trials of adjusted regimens is necessary to ensure appropriate dosing for HIV-infected TB patients on an EFV-based regimen.
Activity of Tedizolid (TR-700) against Well-Characterized Methicillin-Resistant Staphylococcus aureus Strains of Diverse Epidemiological Origins
Authors: Thomson Kenneth S. , Goering Richard V.
Published: April 2013

The
in vitro
activities of tedizolid and 10 antistaphylococcal agents were compared against 111 methicillin-resistant
Staphylococcus aureus
(MRSA) strains from 14 epidemiologically characterized groups. Tedizolid, tigecycline, and daptomycin were the most potent agents, with tedizolid 4-fold more potent than linezolid. Tedizolid, linezolid, and vancomycin were unaffected by epidemiological types. Tigecycline and daptomycin had reduced potency against ST80-MRSA-IV and ST239-MRSA-III, respectively. Overall, tedizolid was highly potent against all MRSA strain types, including those resistant to other classes of drugs.
Extended-Infusion Cefepime Reduces Mortality in Patients with Pseudomonas aeruginosa Infections
Authors: Bauer Karri A. , West Jessica E. , O'Brien James M. , Goff Debra A.
Published: April 2013

In an era of escalating resistance and a lack of new antimicrobial discovery, stewardship programs must utilize knowledge of pharmacodynamics to achieve maximal exposure in the treatment of
Pseudomonas aeruginosa
infections. We evaluated the clinical and economic outcomes associated with extended-infusion cefepime in the treatment of
P. aeruginosa
infections. This single-center study compared inpatients who received cefepime for bacteremia and/or pneumonia admitted from 1 January 2008 through 30 June 2010 (a 30-min infusion of 2 g every 8 h) to those admitted from 1 July 2010 through 31 May 2011 (a 4-h infusion of 2 g every 8 h). The overall mortality was significantly lower in the group that received extended-infusion treatment (20% versus 3%;
P
= 0.03). The mean length of stay was 3.5 days less for patients who received extended infusion (
P
= 0.36), and for patients admitted to the intensive care unit the mean length of stay was significantly less in the extended-infusion group (18.5 days versus 8 days;
P
= 0.04). Hospital costs were $23,183 less per patient, favoring the extended-infusion treatment group (
P
= 0.13). We conclude that extended-infusion treatment with cefepime provides increased clinical and economic benefits in the treatment of invasive
P. aeruginosa
infections.