bluuebunny/crossref_metadata_2025 huggingface dataset:
Zircon in amphibolites from Naxos, Aegean Sea, Greece: origin, significance and tectonic setting
Authors: Bolhar R. , Ring U. , Ireland T. R.
Published: November 2016

We report U–Pb zircon ages of c. 700–550 Ma, 262–220 Ma, 47–38 Ma and 15–14 Ma from amphibolites on Naxos Island in the Aegean extensional province of Greece. The zircon has complex internal structures. Based on cathodoluminescence response, zoning and crosscutting relationships a minimum of four zircon growth stages are identified: inherited core, magmatic core, inner metamorphic (?) rim and an outer metamorphic rim. Trace element compositions of the amphibolites suggest igneous differentiation and crustal assimilation. Zircon solubility as a function of saturation temperatures, Zr content and melt composition indicates that the zircon did not originally crystallize in the mafic bodies but was inherited from felsic precursor rocks, and subsequently assimilated into the mafic intrusives during emplacement. Zircon inheritance is corroborated by the complex, xenocrystic nature of the zircon in one sample. Ages of c. 700–550 Ma and 262–220 Ma are assigned to inherited zircon. Available geochemical data suggest that the 15–14 Ma metamorphic rims grew in situ in the amphibolites, corresponding to a high‐grade metamorphic event at this time. However, the geochemical data cannot conclusively establish if the c. 40 Ma zircon rims also grew in situ, or whether they were inherited along with the xenocrystic cores. Two scenarios for emplacement of the mafic intrusives are discussed: (i) Intrusion during late‐Triassic to Jurassic ocean basin development of the Aegean realm, in which case the 40 Ma zircon rims would have grown in situ, and (ii) emplacement in the Miocene as a result mafic underplating during large‐scale extension. In this case, only the 15–14 Ma metamorphic outer rims would have formed in situ in the amphibolitic host rocks.
Assessment of cubosomal alpha lipoic acid gel efficacy for the aging face: a single‐blinded, placebo‐controlled, right‐left comparative clinical study
Authors: El‐Komy Mohamed , Shalaby Suzan , Hegazy Rehab , Abdel Hay Rania , Sherif Saly , Bendas Ehab
Published: November 2016

Background

A poloxamer solution acting as a vehicle for the lipid base particulate system (cubosome dispersions) containing alpha lipoic acid (ALA) has achieved encouraging results in skin aging.

Objective

Evaluate the efficacy of 5% Cubosomal ALA as an anti‐aging formulation.

Methods

This single‐blinded, placebo‐controlled, comparative study was conducted on 20 females. Patients were instructed to apply a gel formulation containing the active ingredient over the right half of their face and a placebo gel on the left half twice daily for 6 months. Global aesthetic improvement scale (GAIS) was utilized as a measure of clinical progress. The thicknesses of the epidermis and dermis were assessed before and after treatment using an ultrasound biomicroscope.

Results

The GAIS score assessment at 3 and 6 months showed a significantly greater improvement on the right sides in comparison with the left sides. At the end of the treatment period, the mean epidermal thickness significantly increased on the right side in comparison with the left side and the mean dermal thickness increased more on the right side in comparison with the left side; however, this difference was not significant.

Conclusion

5% Cubosomal ALA is an effective and safe modality for improving aging face.
Rethinking presence: a grounded theory of nurses and teleconsultation
Authors: Barrett David
Published: November 2016

Aims and objectives

To develop a theory that offered an evidence‐based insight into the use of teleconsultation by nurses.

Background

Teleconsultation is the use of video to facilitate real‐time, remote interaction between healthcare practitioners and patients. Although its popularity is growing, there is little understanding of how teleconsultation impacts on the role of nurses.

Design

The study adopted a constructivist grounded theory method, supplemented by the use of Straussian analytical approaches.

Methods

Using selective and theoretical approaches, registered nurses with experience of using video in health care were sampled. Data were collected using semi‐structured interviews exploring experiences, knowledge and feelings surrounding teleconsultation. Interviews were recorded, transcribed and subjected to three‐stage, nonlinear manual analysis (open, axial and selective coding).

Results

Theoretical saturation occurred after 17 interviews. The core category identified from the data was ‘nursing presence’ Four subcategories of nursing presence were identified: operational, clinical, therapeutic and social. The degree to which presence could be achieved was dependent upon three influencing factors – enablers, constraints and compensation.

Conclusions

Nurses provide different types of presence during teleconsultation, with the degree of presence dependent on specific characteristics of video‐mediated communication. Where the use of video constrains the delivery of presence, nurses use a range of compensatory mechanisms to enhance patient care.

Relevance to clinical practice

Teleconsultation provides an innovative approach to enhancing the delivery of health care. This study provides nurses with insight into the impact of teleconsultation on their professional role, and an understanding of how best to use video‐mediated communication to support patient care.
Comparison of preoperative hair removal methods for the reduction of surgical site infections: a meta‐analysis
Authors: Shi Dingmei , Yao Yao , Yu Weifei
Published: November 2016

Aims and objectives

To evaluate the efficacy of different methods of preoperative hair removal in reducing surgical site infections.

Background

Surgical site infections are a major source of morbidity and prolonged hospitalisation following surgery. However, there is a lack of data regarding the impact of different preoperative hair removal techniques on the incidence of surgical site infections.

Design

A systematic literature review and meta‐analysis.

Methods

Randomised controlled trials and controlled clinical trials reporting the impact of different methods of preoperative hair removal on reducing surgical site infections were collected through databases, including the Cochrane Library, Joanna Briggs Institute Library, PubMed, Elsevier, EMBASE, Nursing Consult, China Biology Medicine disc, China National Knowledge Infrastructure and Wanfang data. The articles were published from 1 January 1990–15 March 2016. Meta‐analyses were conducted with review manager version 5.0.

Results

Fourteen trials were included (16 comparisons) in the review, including 11 randomised controlled trials and three controlled clinical trials. Interventions in the studies were shaving, clipping, no hair removal and the use of depilatory cream. The meta‐analyses included 7278 patients, from 10 countries. Nine studies compared shaving with no hair removal, four studies compared shaving with clipping, two studies compared shaving with depilatory cream, and one study compared clipping with no hair removal. No significant differences in the frequency of surgical site infections were observed between any of the methods assessed.

Conclusions

No significant differences between shaving, clipping, no hair removal and depilatory cream were observed in the frequency of surgical site infections.

Relevance to clinical practice

Preoperative hair removal should be avoided unless necessary. When it is necessary to remove hair, the existing evidence suggests that clipping is more effective in reducing surgical site infections than shaving or depilatory cream.
Getting evidence‐based pressure ulcer prevention into practice: a process evaluation of a multifaceted intervention in a hospital setting
Authors: Sving Eva , Fredriksson Lennart , Gunningberg Lena , Mamhidir Anna‐Greta
Published: November 2016

Aims and objectives

To describe registered nurses’, assistant nurses’ and first‐line managers’ experiences and perceptions of a multifaceted hospital setting intervention focused on implementing evidence‐based pressure ulcer prevention.

Background

Pressure ulcer prevention is deficient. Different models exist to support implementation of evidence‐based care. Little is known about implementation processes.

Design

A descriptive qualitative approach.

Method

Five focus‐group nurse interviews and five individual first‐line manager interviews were conducted at five Swedish hospital units. Qualitative content analysis was used.

Result

The findings support that the intervention and the implementation process changed the understanding and way of working with pressure ulcer prevention: from treating to preventing. This became possible as ‘Changed understanding enables changed actions – through one's own performance and reflection on pressure ulcer prevention’. Having a common outlook on pressure ulcer prevention, easy access to pressure‐reducing equipment, and external and internal facilitator support were described as important factors for changed practices. Bedside support, feedback and discussions on current results increased the awareness of needed improvements.

Conclusion

The multifaceted intervention approach and the participants’ positive attitudes seemed to be crucial for changing understanding and working more preventatively. The strategies used and the skills of the facilitators need to be tailored to the problems surrounding the context. Feedback discussions among the staff regarding the results of the care provided also appear to be vital.

Relevance to clinical practice

It is crucial that dedicated facilitators are involved to promote the implementation process. A preventative mindset should be strived for. Creating an implementation plan with an outcome and a process evaluation should be emphasised. It is important to give the staff regular feedback on the quality of care and on those occasions allocate time for discussion and reflection.
Effect of HIV infection in the micronuclei frequency on the oral mucosa
Authors: Lima Celina Faig , Alves Monica Ghislaine Oliveira , Furtado Juvencio Jose Duailibe , Marcucci Marcelo , Balducci Ivan , Almeida Janete Dias
Published: November 2016

Background

The genotoxic impact of HIV infection on the oral cavity malignancies is unknown. The aim of this study was to evaluate the effect of HIV infection in micronucleus (MN) frequency on the oral mucosa of HIV+ patients and establish a relationship with early cytogenetic changes in oral carcinogenesis.

Methods

Thirty HIV+ individuals who are under highly active antiretroviral therapy (HAART) and 30 non‐HIV patients were evaluated. Two smears were taken from the lateral border of the tongue and mouth floor and stained by Feulgen. The frequency of MN was examined in 3000 cells per subject under common microscopy.

Results

MN analysis showed no significant difference between groups by Mann–Whitney U‐test for total MNs (P = 0.178). The presence of single MN was greater in control group with statistical significance (P = 0.009), while in HIV group, multiple MNs were exhibited in higher mean.

Conclusions

HIV patients under HAART therapy and low viral load values showed higher frequency of multiple MNs, which, although not statistically significant, may be caused by the action of the Vpr gene, an accessory gene of HIV. These results corroborate the theory of HIV infection cytogenetic damage.
The genetic architecture of novel trophic specialists: larger effect sizes are associated with exceptional oral jaw diversification in a pupfish adaptive radiation
Authors: Martin Christopher H. , Erickson Priscilla A. , Miller Craig T.
Published: November 2016

The genetic architecture of adaptation is fundamental to understanding the mechanisms and constraints governing diversification. However, most case studies focus on loss of complex traits or parallel speciation in similar environments. It is still unclear how the genetic architecture of these local adaptive processes compares to the architecture of evolutionary transitions contributing to morphological and ecological novelty. Here, we identify quantitative trait loci (QTL) between two trophic specialists in an excellent case study for examining the origins of ecological novelty: a sympatric radiation of pupfishes endemic to San Salvador Island, Bahamas, containing a large‐jawed scale‐eater and a short‐jawed molluscivore with a skeletal nasal protrusion. These specialized niches and trophic traits are unique among over 2000 related species. Measurements of the fitness landscape on San Salvador demonstrate multiple fitness peaks and a larger fitness valley isolating the scale‐eater from the putative ancestral intermediate phenotype of the generalist, suggesting that more large‐effect QTL should contribute to its unique phenotype. We evaluated this prediction using an F2 intercross between these specialists. We present the first linkage map for pupfishes and detect significant QTL for sex and eight skeletal traits. Large‐effect QTL contributed more to enlarged scale‐eater jaws than the molluscivore nasal protrusion, consistent with predictions from the adaptive landscape. The microevolutionary genetic architecture of large‐effect QTL for oral jaws parallels the exceptional diversification rates of oral jaws within the San Salvador radiation observed over macroevolutionary timescales and may have facilitated exceptional trophic novelty in this system.
The show must go on? Patients, props and pedagogy in the theatre of the OSCE
Authors: Gormley Gerard J , Hodges Brian D , McNaughton Nancy , Johnston Jennifer L
Published: November 2016

According to Shakespeare, all the world's a stage, and all the men and women merely players. The objective structured clinical examination (OSCE), that most ubiquitous form of assessment in health professions education, offers us a particular instance of this maxim. Comprising at first glance a world of psychometric data, detailed checklists and global rating scales, the OSCE sets out to facilitate the assessment of a candidate's competence in a highly standardised and objective fashion. Despite this clear intention, OSCEs also offer a rich vein of (often unacknowledged) social and cultural processes. In this commentary, we draw on Goffman's dramaturgy metaphor and our experiences to undertake a wry examination of some of the least intended consequences of OSCEs. We take a satirical look at both the potential impact on patients and the pedagogical implications of this form of assessment. We now urge you to sit back, settle in and enjoy the show, as we raise the curtain on this one‐night‐only performance!
Post‐call delirium
Authors: Rush Raphael
Published: November 2016

Although frequently diagnosed in hospital in‐patients, delirium is often recognised but under‐reported in the housestaff population. It is estimated that more than 90% of housestaff will experience regular episodes of post‐call delirium. This paper identifies diagnostic criteria and discusses approaches to treatment.
Developing a pragmatic medical curriculum for the 21st century
Authors: Evans Nicholas R , Warne Ben , Wood Diana F
Published: November 2016

Medical education within a hospital setting presents both opportunities and challenges. The range of educational experiences on offer is often vast, though may be lost in the overworked and convoluted environment of a tertiary centre. As our learners are increasingly consumed by the literal and figurative labyrinths of hospitals and electronic learning logs, are we failing to train them in the skills they need to deliver 21st century health care? In response to this problem we propose a FARCICAL approach: Fostering A Relevant Curriculum that Is Closer to Actual Life.
Cosmologies of selection: lessons from the faculty biscuit tin
Authors: Bartlett Maggie , Bartlett Flora
Published: November 2016

We conducted an ethnography of the faculty biscuit tin as we were interested in the lived experience of the biscuits contained within it. We used a constructivist epistemology, a social constructionist interpretive framework and a phenomenological methodology that included analysis from the perspectives of deixis and cosmology. The biscuits perceived that they were important to a selecting force and that the characteristics of one particular group had a specific value to the selector. Some enduring benefits may derive from the selection of this group, although its attractions were less immediately obvious than those of others. What is immediately attractive may not be the most fit for purpose; lessons for the selection of medical students may arise from this exploration of the selection experiences of biscuits in a faculty biscuit tin.
From the coliseum to the convention centre: a reflection on the current state of medical education conferences and conference‐goers
Authors: Blanchard Rebecca D , Engle Deborah L , Howley Lisa D , Whicker Shari A , Nagler Alisa
Published: November 2016

The advancement of knowledge and development of policy in the field of medical education require critical academic discourse among the most intelligent medical educators; and critical academic discourse requires coffee. In this essay, we reflect on the state of professional development conferences in the field of medical education and the rituals that surround their success. Having begun in ancient Greece, symposia were ripe with debauchery. Today, sedated by the light brown walls of hotel conference centres, symposia are more serious endeavours, engaging men and women in the sometimes turbulent waters of epistemological debate. The abstract submission process (summed up by: ‘Yay! It was accepted for presentation’ [Deep breath] ‘Oh no…it was accepted for presentation’), the ‘juggling act’ of parent attendees, the acting prowess of abstract presenters and the unapologetic approach to buffet eating are all by‐products of the collision of true intellects among medical education scholars. We hold these rituals in high regard and argue that they are required to advance the field of medical education. These rituals bind the walls supporting true progressive thought and innovative research, all fuelled by the glass of wine purchased with that one coveted drink ticket.
Six degrees of separation: the small world of medical education
Authors: Hautz Wolf E , Krummrey Gert , Exadaktylos Aristomenis , Hautz Stefanie C
Published: November 2016

Context

Conventional wisdom has it that everyone on earth is on average only six steps away from knowing any other person through ‘a friend of a friend’. On a local level, however, many people experience that most of their acquaintances know each other. It is thus hard to imagine how such a highly clustered group could be so well connected to the rest of the world. In this paper, we investigate how co‐authorship connects scholars in medical education and whether the six degrees of separation hypothesis also applies to the network of authors in the field.

Methods

We constructed a mathematical graph from publication data obtained on the top three journals in the field and analysed it using social network analysis methods. We found Lorelei Lingard to be one centre of the network of co‐authors and determined the numbers of authors who were one, two or more steps away from her. We further created a website that makes it possible to identify the shortest path from any author in the field to any other, including links to the connecting papers.

Results

The analysis covered 16 653 papers by a total of 24 258 different authors. Co‐authorship connected authors into 68 663 unique pairs, of which 61 937 had co‐authored only one article; 67.43% of all authors were linked to each other through a ‘co‐author of a co‐author’. The average shortest path between any two authors in this network was 5.98 (min 1, max 17); the average distance to Lorelei Lingard was 4.17 (min 1, max 10).

Conclusion

The field of medical education represents what social network analysts term ‘a small world network’. Making the connections between its actors visible may provide a new perspective on social phenomena that occur in this world, including peer review, citation and conference invitations.
Virtual sorting hat™ technology for the matching of candidates to residency training programs
Authors: Gouda Pishoy , Cormican Martin
Published: November 2016

Background

The matching of medical students and trainees to appropriate training programmes poses many challenges, including financial cost and applicant stress. There are few studies that have examined alternatives to the current process of matching candidates to specialist training. Case reports from Hogwarts School of Witchcraft and Wizardry™ have suggested that wearable technology may be used to assign individuals with particular sets of skills and virtues to an appropriate house.

Methods

Investigators developed a modified sorting hat in the form of an online, cross‐sectional survey. The virtual sorting hat was delivered to medical students at the National University of Ireland, Galway, and medical practitioners practising in the associated hospitals and communities. Pearson's chi‐square was used to demonstrate correlations between the allocation of participants to Hogwarts’ houses by virtual sorting hat technology and expressed higher specialist training preference.

Results

Virtual sorting hat technology, applied to medical undergraduates and postgraduates, allocated most participants to Hufflepuff™ (44%) and Ravenclaw™ (32%). Allocation to Gryffindor was associated with preference for surgery and allocation to Slytherin™ with preference for psychiatry.

Conclusion

Virtual sorting hat technology requires significant refinement before application to medical muggles™.
Intraspecific variability improves environmental matching, but does not increase ecological breadth along a wet‐to‐dry ecotone
Authors: Mitchell Rachel M. , Wright Justin P. , Ames Gregory M.
Published: November 2016

It is widely assumed that higher levels of intraspecific variability in one or more traits should allow species to persist under a wider range of environmental conditions. However, few studies have examined whether species that exhibit high variability are found in a wider range of environmental conditions, and whether variability increases the ability of a species to adapt to prevailing ecological gradients. We used four plant functional traits, specific leaf area (SLA), leaf dry matter content (LDMC), leaf carbon to nitrogen ratio (C:N) and maximum plant height in 49 species across a strong environmental gradient to answer three questions: 1) is there evidence for ‘high‐variability’ species (that is, species which show high variability in multiple traits, simultaneously)? 2) are species with more variable traits present across a wider range of environmental conditions than less variable species? And 3) whether more variable species show better trait–environment matching to the prevailing abiotic (soil moisture) gradient at the site? We found little evidence for a ‘high‐variability’ species. Variability was correlated for two leaf traits, SLA and LDMC, while variability in leaf traits and plant height were not correlated. We found little evidence that more variable species were present in more diverse conditions: only variation in SLA was correlated with a wider ecological niche breadth. For plant traits along the soil‐moisture gradient, higher variability led to better trait–environment matching in half of measured traits. Overall, we found little support for the existence of ‘high‐variability’ species, but that variability in SLA is correlated with a wider ecological breadth. We also found evidence that variation in traits can improve trait–environment matching, a relationship which may facilitate our understanding ecological breadth along prevailing gradients, and community assembly on the basis of traits.
Spitz Nevi and Other Spitzoid Neoplasms in Children: Overview of Incidence Data and Diagnostic Criteria
Authors: Dika Emi , Ravaioli Giulia Maria , Fanti Pier Alessandro , Neri Iria , Patrizi Annalisa
Published: November 2016

Spitz nevi are benign melanocytic neoplasms characterized by epithelioid or spindle melanocytes or both. In some rare cases their presentation overlaps with the clinical and histopathologic features of malignant melanoma, so a differential diagnosis can be difficult to make. Intermediate forms between Spitz nevi and malignant melanoma, with unpredictable behavior, have been called atypical Spitz tumors. A literature search was performed to review the clinical, dermoscopic, genetic, and histopathologic aspects of spitzoid tumors. Spitz nevi mainly occur in children, with no predilection for sex, and in young women. Common sites are the head and lower arms, where Spitz nevi present as pink nodules or hyperpigmented plaques. Spitzoid lesions may have diverse dermoscopic patterns: vascular, starburst, globular, atypical, reticular, negative homogeneous, or targetoid. The management of spitzoid lesions can be invasive or conservative; surgical excision is usually reserved for those with doubtful features, whereas clinical and dermoscopic follow‐up is preferred for typical pediatric Spitz nevi. The role of sentinel lymph node biopsy in atypical Spitz tumors is debated. Immunohistochemistry and new molecular techniques such as comparative genomic hybridization, polymerase chain reaction, and fluorescence in situ hybridization offer new diagnostic perspectives, investigating genetic alterations that are specific for malignant melanoma or for Spitz nevi.
Multifocal Congenital Hemangiopericytoma
Authors: Robl Renata , Carvalho Vânia Oliveira , Abagge Kerstin Taniguchi , Uber Marjorie , Lichtvan Leniza Costa Lima , Werner Betina , Mehrdad Nadji Mehrdad
Published: November 2016

Congenital hemangiopericytoma (HPC) is a rare mesenchymal tumor with less aggressive behavior and a more favorable prognosis than similar tumors in adults. Multifocal presentation is even less common than isolated HPC and hence its clinical and histologic recognition may be challenging. A newborn infant with multifocal congenital HPC causing severe deformity but with a favorable outcome after chemotherapy and surgical removal is reported.
Perceived parent and friend support for romantic relationships in emerging adults
Authors: RODRIGUES DAVID , LOPES DINIZ , MONTEIRO LĺGIA , PRADA MARĺLIA
Published: November 2016

Positive close relationships with immediate close network members are associated with healthy adjustment among emerging adults (EA). These influence the initiation and maintenance of romantic relationships. A cross‐sectional study (N = 630) explored the role of perceived parental and friend support for the current romantic relationship in relationship quality among early EA (EEA; 18–21 years) and middle EA (MEA; 22–25 years) heterosexuals. Structural equation modeling results showed that in EEA, greater friend support was associated with greater commitment, satisfaction, and investments, and less quality of alternatives. Greater parental support was associated with greater commitment, satisfaction, and investments in MEA. This research advances literature by showing different associations between sources of social support and relationship quality in two EA age groups.
The association between conditional regard and relationship quality: A daily diary study
Authors: KANAT‐MAYMON YANIV , ARGAMAN YIFTACH , ROTH GUY
Published: November 2016

Research on conditional positive regard (CPR) and conditional negative regard (CNR) has shown that these practices are associated with some maladaptive qualities of romantic relationships. The current study investigated the associations between CPR and CNR and romantic relationship satisfaction using a daily diary methodology. A multilevel analysis of a sample of 80 individuals revealed that both CPR and CNR were negatively linked to relationship satisfaction at the between‐person level. However, at the within‐level, CPR was positively linked to relationship satisfaction, whereas CNR showed a negative association. The findings are discussed within self‐determination theory (E. L. Deci & R. M. Ryan, 2000) and highlight how motivating one's partner by providing positive regard may be satisfying in the short term but controlling in the long run.
Antennal mechanosensors mediate sex pheromone‐induced upwind orientation in the potato tuberworm moth
Authors: Tejima Shin , Ono Tomohiro , Sakuma Masayuki
Published: November 2016

Males of the potato tuberworm moth Phthorimaea operculella (Lepidoptera: Gelechiidae) locate conspecific females by a series of short and straight flights, or ‘hops’. On the floor of a wind tunnel, P. operculella can change their heading angles in response to wind direction shift, suggesting that they detect wind direction and orient upwind when on the ground. It is unlikely that they navigate in wind by vision‐induced optomotor anemotaxis as in many flying moths. To investigate the mechanism of wind direction detection in this species, their orientation behaviour in response to pheromone pulses is observed in a wind tunnel. Intact male moths orient upwind even in complete darkness. After the flagellum of one antenna is amputated, male moths still successfully orient upwind. However, they fail to head upwind when the basal segments of both of their antennae are immobilized with glue. The ability to surge upwind is restored by removing the glue from the antennae. Thus, the results of the present study indicate that males of P. operculella orient upwind in response to mechanoreceptive cues from mechanosensory organs on their antennae. In Lepidoptera, two distinct anemotactic mechanisms of different sensory modalities appear to coexist: optomotor anemotaxis when airborne and the aim‐then‐shoot anemotactic system mediated by antennal mechanoreception when on the ground.
Forecasting Daily Political Opinion Polls Using the Fractionally Cointegrated Vector Auto-Regressive Model
Authors: Nielsen Morten Ørregaard , Shibaev Sergei S.
Published: November 2016

We examine forecasting performance of the recent fractionally cointegrated vector auto-regressive (FCVAR) model. We use daily polling data of political support in the UK for 2010–2015 and compare with popular competing models at several forecast horizons. Our findings show that the four variants of the FCVAR model considered are generally ranked as the top four models in terms of forecast accuracy, and the FCVAR model significantly outperforms both univariate fractional models and the standard cointegrated vector auto-regressive model at all forecast horizons. The relative forecast improvement is higher at longer forecast horizons, where the root-mean-squared forecast error of the FCVAR model is up to 15% lower than that of the univariate fractional models and up to 20% lower than that of the cointegrated vector auto-regressive model. In an empirical application to the 2015 UK general election, the estimated common stochastic trend from the model follows the vote share of the UK Independence Party very closely, and we thus interpret it as a measure of Euroscepticism in public opinion rather than an indicator of the more traditional left–right political spectrum. In terms of prediction of vote shares in the election, forecasts generated by the FCVAR model leading to the election appear to provide a more informative assessment of the current state of public opinion on electoral support than the hung Parliament prediction of the opinion poll.
Cryptococcal infections in solid organ transplant recipients over a 15‐year period at a state transplant center
Authors: Gassiep Ian , McDougall David , Douglas Joel , Francis Ross , Playford Elliott G.
Published: November 2016

Background

The aim of this research paper was to determine the incidence, risk factors, and clinical outcome of solid organ transplant (SOT) recipients diagnosed and treated for cryptococcosis at our institution.

Methods

Retrospective analysis of all patients with SOT diagnosed and treated for cryptococcal infection occurring between January 2001 and December 2015.

Results

Of 102 patients diagnosed with cryptococcal infection, 23 were SOT recipients. Renal transplant accounted for 22/23 cases, of which 13 had meningitis. The annual incidence of infection has risen significantly, and is now greater than 2/1000 prevalent renal transplant recipients. As expected, biochemical factors associated with meningitis include lower glucose on cerebrospinal fluid (CSF) analysis, median 2.4 vs 4.5 mmol/L (P=.02); CSF white blood cell median 50 vs 1/μL (P<.001); CSF protein, median 950 vs 335 mg/L (P=.04). Serum cryptococcal antigen titers were higher in the meningitis cohort, median 512 vs 32 (P=.03). Clinically, headache on admission (odds ratio: 9 [1.29‐63.03], P=.03) and a prolonged length of stay (median of 36 vs 13 days) in the meningitis cohort (P=.02) were significant.

Conclusion

Cryptococcal infection in SOT recipients remains rare; however, there has been a marked increase in cases since 2014. This study reveals a need for increased vigilance for a potential emerging infectious disease. It furthermore highlights the need for ongoing research to further aid early diagnosis, prognostication, management, and screening cost‐effectiveness.
Adequacy of physician documentation and correlation with assessment of transfusion appropriateness: a follow‐up study in the setting of prospective audits and patient blood management
Authors: Madrigal Emilio , Prajapati Shyam , Avadhani Vaidehi , Annen Kyle , Friedman Mark T.
Published: November 2016

BACKGROUND

A previous study in our hospitals correlated suboptimal documentation and failure to justify transfusions. In light of implemented blood‐conservation strategies, including patient blood management (PBM) and prospective audits (PAs), we performed a follow‐up study.

STUDY DESIGN AND METHODS

We reviewed prospectively audited red blood cell (RBC) transfusions received by adult patients from January to July 2014. Survey forms were used to assess the level of documentation and to classify documentation as adequate, intermediate, or inadequate. Transfusions were deemed justified or not by comparisons with hospital transfusion guidelines. We also analyzed the effect of implemented blood‐conservation strategies on our hospital transfusion rates and costs from 2009 to 2015.

RESULTS

During the study period, there were 259 prospectively audited transfusion events (TEs) (one or more RBC units transfused to a patient), of which we reviewed 94 TEs (36.3%) in 87 patients. TEs with suboptimal (intermediate and inadequate) documentation accounted for 46.8% of the reviewed TEs, of which 81.8% could not be justified compared with 18.0% of nonjustified, adequately documented TEs. The correlation between suboptimal documentation and failure to justify transfusion was significant (p < 0.001). This correlation remained even in a comparison between the site with a PBM program and the sites without such a program. Overall transfusion rates declined after the introduction of PA, although the decline was only statistically significant at the sites with a PBM program.

CONCLUSION

Suboptimal transfusion documentation remains problematic and is highly correlated with nonjustifiable transfusions. Newly adopted approaches to minimize blood transfusions have not improved transfusion documentation and corresponding out‐of‐guideline transfusions, although overall transfusions have been reduced by PA, particularly in the setting of a PBM program.
Multifield sub-5 nm overlay in imprint lithography
Authors: Ajay Paras , Cherala Anshuman , Yin Bailey A. , Moon Euclid E. , Fabian Pease R. , Sreenivasan S. V.
Published: November 2016

One significant advantage of imprint lithography (IL) over photolithography is that the field size is not limited optically, and so, throughput can be very high (>100 cm2/s). But, in applications requiring precise (sub-5 nm) overlay, the field size is limited by the distortion (between template and wafer) to about the same field size (26 × 33 mm) as employed in current photolithographic tools for semiconductor integrated circuits. This reduces the throughput of current IL tools to less than that of current photolithographic tools. Here, the authors have, for the first time, created a multifield (dual and quad fields) nanoscale overlay capability by optimally combining (1) Precision mechanical actuators around the periphery of the fields which can correct for magnification and shear over the whole field, and (2) high resolution intrafield isotropic expansion and contraction using an array of local temperature control units. The authors have developed control algorithms for sub-5 nm overlay precision over up to four fields using thermomechanical simulations, and the authors have experimentally validated the approach. This research has the potential to significantly improve IL throughput without compromising nanoscale overlay.
Analytic estimation of line edge roughness for large-scale uniform patterns in electron-beam lithography
Authors: Guo Rui , Lee Soo-Young , Choi Jin , Kim Seom-Beom , Park Sung-Hoon , Shin In-Kyun , Jeon Chan-Uk
Published: November 2016

As the feature size continues to be reduced well below nanoscale, the line edge roughness (LER) will eventually become a resolution-limiting factor in the electron-beam (e-beam) lithography since the LER does not scale with the feature size. Therefore, to achieve the highest resolution possible by the e-beam lithography, the LER needs to be minimized. A simulation-based or experimental approach for estimating and minimizing the LER normally requires a great deal of effort to analyze the relationship between the LER and e-beam parameters and thus is time-consuming. Previously, an analytic method for estimating and minimizing the LER was developed for the case of a single line. In this paper, an extension of the estimation method for large-scale uniform patterns is described. In a large pattern, the exposure distribution over a feature varies with the location within the pattern, and the location dependency is due to the global exposure. The analytic expression of LER derived for a single line is adjusted depending on the location. The amount of adjustment for each of the critical locations is determined by the stochastic information on the global exposure at that location. The LER at a location is obtained through an interpolation using the LERs at the critical locations. The LER evaluated by the analytic expression of LER has been compared with that obtained through simulation.
Internal tides and deep diel fades in acoustic intensity
Authors: White Andrew W. , Henyey Frank S. , Andrew Rex K. , Mercer James A. , Worcester Peter F. , Dzieciuch Matthew A. , Colosi John A.
Published: November 2016

A mechanism is presented by which the observed acoustic intensity is made to vary due to changes in the acoustic path that are caused by internal-tide vertical fluid displacements. The position in range and depth of large-scale caustic structure is determined by the background sound-speed profile. Internal tides cause a deformation of the background profile, changing the positions of the caustic structures—which can introduce intensity changes at a distant receiver. Gradual fades in the acoustic intensity occurring over timescales similar to those of the tides were measured during a low-frequency (284-Hz) acoustic scattering experiment in the Philippine Sea in 2009 [White et al., J. Acoust. Soc. Am. 134(4), 3347–3358 (2013)]. Parabolic equation and Hamiltonian ray-tracing calculations of acoustic propagation through a plane-wave internal tide environmental model employing sound-speed profiles taken during the experiment indicate that internal tides could cause significant gradual changes in the received intensity. Furthermore, the calculations demonstrate how large-scale perturbations to the index of refraction can result in variation in the received intensity.
Papers of note in
Science
Authors: VanHook Annalisa M.
Published: November 2016

This week’s articles show that some plant photoreceptors can also detect temperature, enzymes that synthesize a plant defense metabolite assemble on demand, not all phosphorylation of tau promotes neurodegeneration, and neurons thought to be part of the parasympathetic nervous system are actually sympathetic.
Activating the MAPK pathway with a kinase instead of a GTPase
Authors: VanHook Annalisa M.
Published: November 2016

The kinase PBL27 links activation of a pathogen recognition receptor to activation of immune signaling in
Arabidopsis thaliana
.
Cancer, host metabolism, and immunotherapy
Authors: Ferrarelli Leslie K.
Published: November 2016

Tumor-induced metabolic stress associated with cachexia suppresses the antitumor immune response in mice.
Results of a Doravirine-Atorvastatin Drug-Drug Interaction Study
Authors: Khalilieh Sauzanne , Yee Ka Lai , Sanchez Rosa I. , Triantafyllou Ilias , Fan Li , Maklad Noha , Jordan Heather , Martell Maureen , Iwamoto Marian
Published: November 2016

Doravirine is a novel, highly potent, nonnucleoside reverse transcriptase inhibitor that is administered once daily and that is in development for the treatment of HIV-1 infection.
In vitro
and clinical data suggest that doravirine is unlikely to cause significant drug-drug interactions via major drug-metabolizing enzymes or transporters. As a common HIV-1 infection comorbidity, hypercholesterolemia is often treated with statins, including the commonly prescribed atorvastatin. Atorvastatin is subject to drug-drug interactions with cytochrome P450 3A4 (CYP3A4) inhibitors. Increased exposure due to CYP3A4 inhibition may lead to serious adverse events (AEs), including rhabdomyolysis. Furthermore, atorvastatin is a substrate for breast cancer resistance protein (BCRP), of which doravirine may be a weak inhibitor; this may increase atorvastatin exposure. The potential of doravirine to affect atorvastatin pharmacokinetics was investigated in a two-period, fixed-sequence study in healthy individuals. In period 1, a single dose of atorvastatin at 20 mg was administered followed by a 72-h washout. In period 2, doravirine at 100 mg was administered once daily for 8 days, with a single dose of atorvastatin at 20 mg concomitantly being administered on day 5. Sixteen subjects were enrolled, and 14 completed the trial; 2 discontinued due to AEs unrelated to the treatment. The atorvastatin area under the curve from time zero to infinity was similar with and without doravirine (geometric mean ratio [GMR] for doravirine-atorvastatin/atorvastatin, 0.98; 90% confidence interval [CI], 0.90 to 1.06), while the maximum concentration decreased by 33% (GMR for doravirine-atorvastatin/atorvastatin, 0.67; 90% CI, 0.52 to 0.85). These changes were deemed not to be clinically meaningful. Both of the study drugs were generally well tolerated. Doravirine had no clinically relevant effect on atorvastatin pharmacokinetics in healthy subjects, providing support for the coadministration of doravirine and atorvastatin.
Exploring the Role of the Ω-Loop in the Evolution of Ceftazidime Resistance in the PenA β-Lactamase from Burkholderia multivorans, an Important Cystic Fibrosis Pathogen
Authors: Papp-Wallace Krisztina M. , Becka Scott A. , Taracila Magdalena A. , Zeiser Elise T. , Gatta Julian A. , LiPuma John J. , Bonomo Robert A.
Published: November 2016

The unwelcome evolution of resistance to the advanced generation cephalosporin antibiotic, ceftazidime is hindering the effective therapy of
Burkholderia cepacia
complex (BCC) infections. Regrettably, BCC organisms are highly resistant to most antibiotics, including polymyxins; ceftazidime and trimethoprim-sulfamethoxazole are the most effective treatment options. Unfortunately, resistance to ceftazidime is increasing and posing a health threat to populations susceptible to BCC infection. We found that up to 36% of 146 tested BCC clinical isolates were nonsusceptible to ceftazidime (MICs ≥ 8 μg/ml). To date, the biochemical basis for ceftazidime resistance in BCC is largely undefined. In this study, we investigated the role of the Ω-loop in mediating ceftazidime resistance in the PenA β-lactamase from
Burkholderia multivorans
, a species within the BCC. Single amino acid substitutions were engineered at selected positions (R164, T167, L169, and D179) in the PenA β-lactamase. Cell-based susceptibility testing revealed that 21 of 75 PenA variants engineered in this study were resistant to ceftazidime, with MICs of >8 μg/ml. Under steady-state conditions, each of the selected variants (R164S, T167G, L169A, and D179N) demonstrated a substrate preference for ceftazidime compared to wild-type PenA (32- to 320-fold difference). Notably, the L169A variant hydrolyzed ceftazidime significantly faster than PenA and possessed an ∼65-fold-lower apparent

K
i

(

K
i

app
) than that of PenA. To understand why these amino acid substitutions result in enhanced ceftazidime binding and/or turnover, we employed molecular dynamics simulation (MDS). The MDS suggested that the L169A variant starts with the most energetically favorable conformation (−28.1 kcal/mol), whereas PenA possessed the most unfavorable initial conformation (136.07 kcal/mol). In addition, we observed that the spatial arrangement of E166, N170, and the hydrolytic water molecules may be critical for enhanced ceftazidime hydrolysis by the L169A variant. Importantly, we found that two clinical isolates of
B. multivorans
possessed L169 amino acid substitutions (L169F and L169P) in PenA and were highly resistant to ceftazidime (MICs ≥ 512 μg/ml). In conclusion, substitutions in the Ω-loop alter the positioning of the hydrolytic machinery as well as allow for a larger opening of the active site to accommodate the bulky R1 and R2 side chains of ceftazidime, resulting in resistance. This analysis provides insights into the emerging phenotype of ceftazidime-resistant BCC and explains the evolution of amino acid substitutions in the Ω-loop of PenA of this significant clinical pathogen.
The Staphylococcus aureus AirSR Two-Component System Mediates Reactive Oxygen Species Resistance via Transcriptional Regulation of Staphyloxanthin Production
Authors: Hall Jeffrey W. , Yang Junshu , Guo Haiyong , Ji Yinduo
Published: November 2016

Staphylococcus aureus
is an important opportunistic pathogen and is the etiological agent of many hospital- and community-acquired infections. The golden pigment, staphyloxanthin, of
S. aureus
colonies distinguishes it from other staphylococci and related Gram-positive cocci. Staphyloxanthin is the product of a series of biosynthetic steps that produce a unique membrane-embedded C
30
golden carotenoid and is an important antioxidant. We observed that a strain with an inducible
airR
overexpression cassette had noticeably increased staphyloxanthin production compared to the wild-type strain under aerobic culturing conditions. Further analysis revealed that depletion or overproduction of the AirR response regulator resulted in a corresponding decrease or increase in staphyloxanthin production and susceptibility to killing by hydrogen peroxide, respectively. Furthermore, the genetic elimination of staphyloxanthin during AirR overproduction abolished the protective phenotype of increased staphyloxanthin production in a whole-blood survival assay. Promoter reporter and gel shift assays determined that the AirR response regulator is a direct positive regulator of the staphyloxanthin-biosynthetic operon,
crtOPQMN
, but is epistatic to alternative sigma factor B. Taken together, these data indicate that AirSR positively regulates the staphyloxanthin-biosynthetic operon
crtOPQMN
, promoting survival of
S. aureus
in the presence of oxidants.