bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized Trial of Ketorolac vs Sumatripan vs Placebo Nasal Spray (KSPN) for Acute Migraine
Authors: Rao Aruna S. , Gelaye Bizu , Kurth Tobias , Dash Paul D. , Nitchie Haley , Peterlin B. Lee
Published: February 2016

Objective

To compare the efficacy of ketorolac nasal spray (NS) vs placebo and sumatriptan NS for the acute treatment of migraine.

Methods

This was a randomized, double‐blind, placebo and active‐comparator, crossover study. Adult migraineurs were randomized to ketorolac NS 31.5 mg, sumatriptan NS 20 mg, or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack. Patients seeking headache care at a headache center or in response to community advertisement were recruited. Adult participants with episodic migraine who experienced ≥2 migraine attacks per month were eligible for the Ketorolac vs Sumatriptan vs Placebo Nasal Spray migraine study. Participants were randomized to treatment arms by a research pharmacist, in a 1:1:1 ratio using computer‐generated lists. The primary outcome was 2‐hour pain relief. Secondary outcomes included 2‐hour pain freedom and absence of migraine associated symptoms, and 24‐hour sustained pain relief and pain freedom.

Results

Of the 72 randomized participants, 54 (75%) treated at least one attack and 49 (68%) completed all three treatments, for a total of 152 treated migraine attacks. Both ketorolac NS (72.5%, P < .001) and sumatriptan NS (69.4%, P = .001) were more effective than placebo (38.3%) for 2‐hour pain relief and 2‐hour pain freedom (ketorolac: 43.1%, P = .004; sumatriptan: 36.7%, P = .046; placebo: 18.4%). Ketorolac NS, but not sumatriptan NS, was more effective than placebo in 2‐hour absence of nausea. Both ketorolac NS and sumatriptan NS were more effective than placebo for 24‐hour sustained pain relief (ketorolac: 49%, P < .001; sumatriptan: 31%, P = .01, placebo: 20%). Only ketorolac NS was superior to placebo for 24‐hour (ketorolac: 35.3%, P = .003; sumatriptan: 22.4%, P = .18, placebo: 12.2%) sustained pain freedom. Nasal burning and dysgeusia were the most common adverse effects for active treatments.

Conclusions

This study supports that ketorolac NS is superior to placebo and that it is non‐inferior to sumatriptan NS for the acute abortive treatment of migraine.
Prevalence of anaemia and iron deficiency in Portugal: the EMPIRE study
Authors: Fonseca C. , Marques F. , Robalo Nunes A. , Belo A. , Brilhante D. , Cortez J.
Published: February 2016

Background

Anaemia and iron deficiency are major public health problems with great implications on quality of life.

Aims

To establish the general prevalence of anaemia and iron deficiency in the adult Portuguese population and the prevalence by age, gender and region.

Methods

This was a population‐based, cross‐sectional study (EMPIRE study) based on a representative sample of 7980 adults residing in mainland Portugal, which were selected using a random route sampling method. Levels of haemoglobin, ferritin, creatinine and C‐reactive protein were measured by Point‐of‐Care assays; participants also completed a questionnaire about demography and medical history.

Results

The measured prevalence of anaemia was 19.9% (95% confidence interval: 19.0–20.8%); 84% of cases were previously undiagnosed. Anaemia was more prevalent among women (20.8%), young adults (18−34 years) (22.8–30.5%), older adults (21.0%), and pregnant women (54.2%). Anaemia varied across regions: from 15.5% in the Center region to 24.9% in the South. Iron deficiency was also highly prevalent: 16.7% (ferritin <15 ng/mL), 31.9% (<30 ng/mL), 53.3% (<50 ng/mL) and 84.3% (<100 ng/mL). Iron deficiency anaemia represented most anaemia cases: 29.0% (ferritin <15 ng/mL), 54.8% (<30 ng/mL), 75.4% (<50 ng/mL) and 92.5% (<100 ng/mL).

Conclusion

Anaemia and iron deficiency are highly prevalent in Portugal and largely undiagnosed. Women, young adults and older individuals are more prone to present these conditions and there are marked regional asymmetries. Nationwide strategies for prevention, diagnosis and treatment of these conditions should be implemented.
Disorganization of the splenic microanatomy in ageing mice
Authors: Aw Danielle , Hilliard Lucy , Nishikawa Yoshio , Cadman Emma T. , Lawrence Rachel A. , Palmer Donald B.
Published: February 2016

The precise mechanisms responsible for immunosenescence still remain to be determined, however, considering the evidence that disruption of the organization of primary and secondary lymphoid organs results in immunodeficiency, we propose that this could be involved in the decline of immune responses with age. Therefore, we investigated the integrity of the splenic microarchitecture in mice of increasing age and its reorganization following immune challenge in young and old mice. Several differences in the anatomy of the spleen with age in both the immune and stromal cells were observed. There is an age‐related increase in the overall size of the white pulp, which occurs primarily within the T‐cell zone and is mirrored by the enlargement of the T‐cell stromal area, concurrent to the distinct boundary between T cells and B cells becoming less defined in older mice. In conjunction, there appears to be a loss of marginal zone macrophages, which is accompanied by an accumulation of fibroblasts in the spleens from older animals. Furthermore, whereas the reorganization of the white pulp is resolved after several days following antigenic challenge in young animals, it remains perturbed in older subjects. All these age‐related changes within the spleen could potentially contribute to the age‐dependent deficiencies in functional immunity.
Metaphor as Analogy: Reproduction and Production of Legal Concepts
Authors: Condello Angela
Published: February 2016

Metaphor can be compared to analogy because they both have, additionally to their rhetorical competence, an epistemic force. Through analogy legal concepts are reproduced according to similarity; reproduction is always a new production and thus analogy and metaphor in law have a poietic force. The reproduction and production (poiesis) of legal concepts through metaphor by analogy concerns the interference between classificatory operations in law and legal epistemology: in every categorization of the unknown by means of the known, legal ontology and legal epistemology intersect.
Flesh of the Law: Material Legal Metaphors
Authors: Philippopoulos‐Mihalopoulos Andreas
Published: February 2016

Existing legal metaphors, even the predominantly spatial and corporeal ones, paradoxically perpetuate a dematerialized impression of the law. This is because they depict the law as universal, adversarial, and court‐based, thus ignoring alternative legalities. Instead, there is a need to employ more radically material metaphors, in line with the material turn in law and other disciplines, in order to allow law's materiality to come forth. I explore the connection between language and matter (the ‘flesh’ of the law) through legal, linguistic, and art theory, and conclude by suggesting four characteristics of material legal metaphors.
133Cs and 23Na MAS NMR Spectroscopy of Molybdate Crystallization in Model Nuclear Glasses
Authors: Kroeker Scott , Schuller Sophie , Wren John E. C. , Greer Brandon J. , Mesbah Adel
Published: February 2016

Sodium borosilicate base glasses modeled on French nuclear waste materials were prepared to test the dependence of crystallization product quantity and distribution on cesium‐ and molybdenum‐loading and glass cooling rate. Scanning electron microscopy shows the presence of micrometer‐sized domains of Mo‐rich crystalline precipitates. X‐ray diffraction patterns are complex but reveal the presence of sodium molybdates and CsNaMoO4·2H2O. 133Cs and 23Na magic‐angle spinning NMR spectroscopy exhibit distinct peaks for glassy and crystalline phases which can be quantified to obtain the identities of the individual compounds that are formed as well as the fractions of these nuclei in particular crystalline phases. In these model systems, 1 mol% Mo can be entirely incorporated into the glassy network whereas 2.5 and 5 mol% Mo produce significant quantities of crystalline phases, with little dependence on cooling rate. Cesium content appears to have a weak influence on crystallization behavior. Sodium molybdate and sodium‐cesium molybdate hydrate are the dominant devitrification phases in all cases.
Vasovagal Syncope: Hypothesis Focusing on Its Being a Clinical Feature Unique to Humans
Authors: BLANC JEAN‐JACQUES , BENDITT DAVID G.
Published: February 2016

Vasovagal Syncope

Humans live primarily in the upright position; as a result, there is a constant struggle between gravity and needed supply of blood flow to the brain. In certain circumstances brain blood supply may become temporarily insufficient, resulting in syncope. Among the numerous causes of syncope in humans, vasovagal syncope (VVS) is by far the most common. However, despite intensive research, many aspects of the pathophysiology of VVS remain unknown; among these, one of the least well understood is the basis for why VVS is restricted, among vertebrates, to Homo sapiens. In this manuscript we review proposals that have been offered in an attempt to address the issue of the origin of VVS and, although highly speculative, we suggest a new hypothesis (the “brain theory”) to try to address the question of why humans, to the exclusion of other species, remain susceptible to VVS. This theory suggests that VVS evolved to offer protection to the brain's functional integrity under certain conditions of severe threat. Although seemingly a disadvantageous evolutionary adaptation, the faint causes the body to take on a gravitationally neutral position, and thereby provides a better chance of restoring brain blood supply and preserving long‐term brain function.
Clinical Presentation and Outcomes by Sex in Arrhythmogenic Right Ventricular Cardiomyopathy: Findings from the North American ARVC Registry
Authors: CHOUDHARY NAILA , TOMPKINS CHRISTINE , POLONSKY BRONISLAVA , MCNITT SCOTT , CALKINS HUGH , MARK ESTES N. A. , KRAHN ANDREW D. , LINK MARK S. , MARCUS FRANK I. , TOWBIN JEFFREY A. , ZAREBA WOJCIECH
Published: February 2016

Clinical Presentation and Outcomes

Background

Sex differences in clinical presentation and outcomes of hereditary arrhythmias are commonly reported. We aimed to compare clinical presentation and outcomes in men and women with arrhythmogenic right ventricular cardiomyopathy (ARVC) enrolled in the North American ARVC Registry.

Methods

A total of 125 ARVC probands (55 females, mean age 38 ± 12; 70 males, mean age 41 ± 15) diagnosed, as either “affected” or “borderline” were included. Baseline clinical characteristics and time‐dependent outcomes including syncope, ventricular tachycardia (VT), fast VT (>240 bpm), ventricular fibrillation (VF), and death were compared between males and females.

Results

The percentage of ARVC subjects diagnosed as “affected” (84% vs. 89%; P = 0.424) or “borderline” (16% vs. 11%; P = 0.424) was similar between females and males. Among the baseline characteristics, inverted T‐waves in V2 trended to be more common in women (P = 0.09), whereas abnormal signal‐averaged ECGs (SAECGs; P < 0.001) and inducible VT/VF (P = 0.026) were more frequent in men. During a mean follow‐up of 37 ± 20 months, the probability of ICD‐recorded VT/VF or death was not significantly different between men and women (P = 0.456). However, there was a trend toward lower risk of fast VT/VF or death in women compared to men (hazard ratio 0.41, 95% CI 0.151–1.113, P = 0.066). Abnormal SAECG and evidence of intramyocardial fat by cardiac MRI was associated with adverse outcomes in men (P = 0.006 and 0.02 respectively).

Conclusion

In the North American ARVC Registry, we found similar frequency of “affected” and “borderline” subjects between men and women. Sex‐related differences were observed in baseline ECG, SAECG, Holter‐recorded ventricular arrhythmias, and VT inducibility. Men showed a trend toward greater risk of fast VT than women.
Dispelling myths concerning pigmented skin lesions
Authors: Piccolo V. , Russo T. , Giacomel J. , Lallas A. , Alfano R. , Argenziano G.
Published: February 2016

The history of medicine is replete with examples of debunked myths, and in daily clinical dermatological practice, we must still counter many misconceptions regarding pigmented lesions, both with patients and other medical practitioners. Debunking myths and attempting to explain the reasons for these erroneous beliefs are the purposes of this review. The literature review has been partially guided by the results obtained from an online questionnaire conducted on an Italian website (www.vediamocichiara.it) from February 15, 2015 to March 15, 2015. The remaining discussed were selected on the basis of the existing literature and our personal experience. In order to explore these misconceptions, the following are the seven most salient questions that require investigation: (i) Is it dangerous to excise moles?; (ii) Is it dangerous to traumatize moles?; (iii) Are plantar moles worrisome?; (iv) Is it necessary to selectively apply sunscreen to moles?; (v) Is it inadvisable to partially biopsy a melanoma?; (vi) Do moles turn into melanoma?; and (vii) Is it necessary to perform sentinel lymph node biopsy for thin melanomas and for atypical Spitz naevi? Myths are ubiquitous, being prevalent in dermatological practice, with many of them concerning pigmented skin lesions. By encouraging critical analysis by patients and medical practitioners, the birth and perpetuation of myths can potentially be minimized, for the ultimate benefit of patients. This requires a scientific approach to be rigorously applied to dermatology, with critical questioning of unsubstantiated hypotheses including those emanating from the mass media as well as from respected sources.
Prognostic impact of the number of retrieved lymph nodes in patients with gastric cancer
Authors: Okajima Wataru , Komatsu Shuhei , Ichikawa Daisuke , Kosuga Toshiyuki , Kubota Takeshi , Okamoto Kazuma , Konishi Hirotaka , Shiozaki Atsushi , Fujiwara Hitoshi , Otsuji Eigo
Published: February 2016

Background

In gastric cancer, although at least 16 lymph nodes of retrieved lymph nodes (RLNs) are recommended for nodal staging in Japanese Classification of Gastric Carcinoma and TNM classifications, we wished to clarify their appropriateness.

Study Design

A total of 1289 consecutive gastric cancer patients, who underwent gastrectomy between 1997 and 2011, were analyzed retrospectively.

Results

(i) The patients were divided into two groups using a cut‐off RLN number of 16 (RLN < 16 or RLN ≥ 16). There were significant differences in the survival rates of patients in pStage II (P < 0.0001) and III (P = 0.0009), but not those of patients in pStage I (P = 0.0627) and IV (P = 0.1553). (ii) In 498 consecutive patients in pStage II and III, compared with patients in the RLN ≥ 16 group, those in the RLN < 16 group had a significantly higher incidence of older age (P = 0.0004) and positive lymph node ratio (PLNR) (P < 0.0001). Univariate and multivariate analyses showed that an RLN number of less than 16 was an independent poor prognostic factor (P < 0.0001, HR 2.48 [95% CI: 1.60–3.70]). (iii) A cut‐off RLN number of 16 could cause the stage migration effect in pStage II or III patients. A cut‐off RLN number of 25 or more could eliminate the prognostic effect.

Conclusion

The RLN number may potentially affect the prognosis and the stage migration in pStage II or III gastric cancer patients. An RLN number of 25 or more could be sufficient for nodal staging.
Negotiated autonomy in diabetes self‐management: the experiences of adults with intellectual disability and their support workers
Authors: Whitehead L. C. , Trip H. T. , Hale L. A. , Conder J.
Published: February 2016

Background

The basic human right of autonomy is underpinned by the ability to practice decision‐making. The rights of people with disabilities to engage in autonomous decision‐making are promoted as best practice and includes decisions around health and self‐care. Little is known about autonomy in the field of long‐term condition management. This paper explores how people with intellectual disabilities (ID) and their support workers experience and practice autonomy in relation to the management of diabetes.

Methods

Semi‐structured interviews were completed in residential and independent living settings with people living with an ID and type 1 (N = 8) or type 2 (N = 6) diabetes and their support workers (N = 17). The participant with ID's support worker was present as requested; however, the interviews were run separately with each participant rather than jointly. Thematic analysis was undertaken, and a constructivist lens informed both data collection and analysis.

Results

The analysis revealed a strong process of negotiated autonomy between people with ID and their support workers in relation to the daily management of diabetes. During times of transition, roles in relation to diabetes management were renegotiated, and the promotion of autonomy was prefaced within the context of risk and client safety. Goals to increase independence were drivers for negotiating greater autonomy.

Conclusions

The successful negotiation of autonomy in relation to diabetes illustrates the potential for people with ID to play a key role in the management of long‐term health conditions. The study highlights the primacy of developing decision‐making skills among people with ID. Promoting opportunities for decision‐making and an ethos of supported decision‐making through person‐centred planning are all vital in working towards enhancing autonomy.
Worrying about the Stock Market: Evidence from Hospital Admissions
Authors: ENGELBERG JOSEPH , PARSONS CHRISTOPHER A.
Published: February 2016

Using individual patient records for every hospital in California from 1983 to 2011, we find a strong inverse link between daily stock returns and hospital admissions, particularly for psychological conditions such as anxiety, panic disorder, and major depression. The effect is nearly instantaneous (within the same day) for psychological conditions, suggesting that anticipation over future consumption directly influences instantaneous utility.
“Lucas” in the Laboratory
Authors: ASPAROUHOVA ELENA , BOSSAERTS PETER , ROY NILANJAN , ZAME WILLIAM
Published: February 2016

We study the Lucas asset pricing model in a controlled setting. Participants trade two long‐lived securities in a continuous open‐book system. The experimental design emulates the stationary, infinite‐horizon setting of the model and incentivizes participants to smooth consumption across periods. Consistent with the model, prices align with consumption betas and comove with aggregate dividends, particularly so when risk premia are higher. Trading significantly increases consumption smoothing compared to autarky. Nevertheless, as in field markets, prices are excessively volatile. The noise corrupts traditional generalized method of moment tests. Choices display substantial heterogeneity, with no subject representative for pricing.
Circadian rhythm of calciotropic hormones, serum calcium, phosphorus and magnesium during the shortest and longest days of the year in horses in New Zealand
Authors: Azarpeykan S. , Dittmer K. E. , Gee E. K. , Marshall J. C. , Elder P. , Acke E. , Thompson K. G.
Published: February 2016

A study was conducted to determine the circadian rhythms and trends of vitamin D metabolites including 25‐hydroxyvitamin D3, 25‐hydroxyvitamin D2, 1,25‐dihydroxyvitamin D and parathyroid hormone, in addition to serum calcium, phosphorus and magnesium concentrations in horses over 48 h on the shortest and longest days of the year in 2013. Five healthy adult horses (Equus caballus) were on a constant pasture feeding regimen, and blood samples were collected from each horse every 3 h over a 48‐h period, starting at 07:00 PM on day one and finishing at 07:00 PM on day three, for the measurement of calciotropic hormones and electrolytes. There was a significant difference between the serum concentration of calciotropic hormones, iCa, tCa, P and tMg between the shortest (winter) and longest (summer) days of the year in horses. Serum concentration of 25OHD3 was very low and mostly undetectable. Serum iCa, 1,25(OH)2D and PTH concentrations clearly showed a circadian rhythm on the longest days of the year and serum tCa, P and tMg concentrations showed a diurnal pattern on the longest days (summer) of the year. None of the analytes showed any circadian rhythm on the shortest days (winter) of the year. The result of this study could have significant relevance to equine athletes travelling to international equestrian competitions and facing a huge time and seasonal differences that might affect their ability to adjust their circadian rhythms to new time zones.
Estimates of the quality of complementary feeding among Vietnamese infants aged 6−23 months varied by how commercial baby cereals were classified in 24‐h recalls
Authors: Tuan Nguyen T. , Withers Mellissa , Frongillo Edward A. , Hajeebhoy Nemat
Published: February 2016

The World Health Organization's (WHO) standardized questionnaire for assessing infant and young child feeding practices does not include commercial baby cereals (CBC), which are derived from several food groups and are fortified with micronutrients. We examined how different scenarios for classifying CBC affect estimates of the quality of complementary feeding in children ages 6−23 months in Vietnam in 2014 (n = 4811). In addition to the WHO standardized 24‐h recall questionnaire for infant and young child feeding, we asked mothers about the consumption of CBC. The five resulting scenarios were S1 – omitted CBC; S2 – CBC classified as grains; S3 – as grains and dairy; S4 – as grains, dairy and fruit/vegetables; and S5 – as grains, dairy, fruit/vegetables and any others. Including CBC resulted in 4−11 percentage points higher in the prevalence of children who were fed each of the six food groups compared with what was reported in the WHO standardized questionnaire. Minimum dietary diversity (% fed ≥ 4 out of the 7 food groups) was higher in S5 (90%) than in S1 (84%), S2 (84%), S3 (85%) and S4 (86%). Minimum acceptable diet was also higher in scenarios S5 (80%) than in S1 (74%), S2 (75%), S3 (75%) and S4 (77%). Consumption of iron‐rich foods was 94% when CBC was accounted, which was higher than the alternative scenario (89%). In summary, when CBC were included, population‐level estimates of dietary quality were higher than when CBC were omitted. Guidance is required from the WHO about how to account for the consumption of CBC when estimating the quality of complementary feeding.
Role of selection and gene flow in population differentiation at the edge vs. interior of the species range differing in climatic conditions
Authors: Volis S. , Ormanbekova D. , Shulgina I.
Published: February 2016

Evaluating the relative importance of neutral and adaptive processes as determinants of population differentiation across environments is a central theme of evolutionary biology. We applied theQST–FSTcomparison flanked by a direct test for local adaptation to infer the role of climate‐driven selection and gene flow in population differentiation of an annual grassAvena sterilisin two distinct parts of the species range, edge and interior, which represent two globally different climates, desert and Mediterranean. In a multiyear reciprocal transplant experiment, the plants of desert and Mediterranean origin demonstrated home advantage, and population differentiation in several phenotypic traits related to reproduction exceeded neutral predictions, as determined by comparisons ofQSTvalues with theoreticalFSTdistributions. Thus, variation in these traits likely resulted from local adaptation to desert and Mediterranean environments. The two separate common garden experiments conducted with different experimental design revealed that two population comparisons, in contrast to multi‐population comparisons, are likely to detect population differences in virtually every trait, but many of these differences reflect effects of local rather than regional environment. We detected a general reduction in neutral (SSR) genetic variation but not in adaptive quantitative trait variation in peripheral desert as compared with Mediterranean core populations. On the other hand, the molecular data indicated intensive gene flow from the Mediterranean core towards desert periphery. Although species range position in our study (edge vs. interior) was confounded with climate (desert vs. Mediterranean), the results suggest that the gene flow from the species core does not have negative consequences for either performance of the peripheral plants or their adaptive potential.
Long‐term salinity tolerance is accompanied by major restructuring of the coral bacterial microbiome
Authors: Röthig Till , Ochsenkühn Michael A. , Roik Anna , van der Merwe Riaan , Voolstra Christian R.
Published: February 2016

Scleractinian corals are assumed to be stenohaline osmoconformers, although they are frequently subjected to variations in seawater salinity due to precipitation, freshwater run‐off and other processes. Observed responses to altered salinity levels include differences in photosynthetic performance, respiration and increased bleaching and mortality of the coral host and its algal symbiont, but a study looking at bacterial community changes is lacking. Here, we exposed the coral Fungia granulosa to strongly increased salinity levels in short‐ and long‐term experiments to disentangle temporal and compartment effects of the coral holobiont (i.e. coral host, symbiotic algae and associated bacteria). Our results show a significant reduction in calcification and photosynthesis, but a stable microbiome after short‐term exposure to high‐salinity levels. By comparison, long‐term exposure yielded unchanged photosynthesis levels and visually healthy coral colonies indicating long‐term acclimation to high‐salinity levels that were accompanied by a major coral microbiome restructuring. Importantly, a bacterium in the family Rhodobacteraceae was succeeded by Pseudomonas veronii as the numerically most abundant taxon. Further, taxonomy‐based functional profiling indicates a shift in the bacterial community towards increased osmolyte production, sulphur oxidation and nitrogen fixation. Our study highlights that bacterial community composition in corals can change within days to weeks under altered environmental conditions, where shifts in the microbiome may enable adjustment of the coral to a more advantageous holobiont composition.
At least some meiofaunal species are not everywhere. Indication of geographic, ecological and geological barriers affecting the dispersion of species of Ototyphlonemertes (Nemertea, Hoplonemertea)
Authors: Leasi Francesca , Andrade Sónia Cristina da Silva , Norenburg Jon
Published: February 2016

Most meiofaunal species are known to have a broad distribution with no apparent barriers to their dispersion. However, different morphological and/or molecular methods supported patterns of diversity and distribution that may be different among taxa while also conflicting within the same group. We accurately assessed the patterns of geographic distribution in actual genetic species of a marine meiofaunal animal model: Ototyphlonemertes. Specimens were collected from several sites around Europe, Northern and Central America, Southern America, Pacific Islands and Asia. We sequenced regions of two mitochondrial and two nuclear genes. Using single‐gene, a concatenated data set, multilocus approaches and different DNA taxonomy methods, we disentangled the actual diversity and the spatial structures of haplotypes and tested the possible correlation between genetic diversity and geographic distance. The results show (i) the importance of using several genes to uncover both diversity and highlight phylogeographic relationships among species and that (ii) independent genetic evolutionary entities have a narrower distribution than morphological species. Moreover, (iii) a Mantel test supported a positive correlation between genetic and geographical distance. By sampling from the two sides of Isthmus of Panama, we were additionally able to identify lineage divergence times that are concordant with vicariance mechanisms caused by the geological closure of the seaway across the Isthmus. We therefore propose that in addition to distance, other geological and ecological conditions are also barriers to the dispersion of and gene flow in marine meiofaunal organisms.
Genomewide introgressive hybridization patterns in wild Atlantic salmon influenced by inadvertent gene flow from hatchery releases
Authors: Ozerov M. Y. , Gross R. , Bruneaux M. , Vähä J.‐P. , Burimski O. , Pukk L. , Vasemägi A.
Published: February 2016

Many salmonid fish populations are threatened by genetic homogenization, primarily due to introgressive hybridization with hatchery‐reared conspecifics. By applying genomewide analysis using two molecular marker types (1986 SNPs and 17 microsatellites), we assessed the genetic impacts of inadvertent gene flow via straying from hatchery releases on wild populations of Atlantic salmon in the Gulf of Finland, Baltic Sea, over 16 years (1996–2012). Both microsatellites and SNPs revealed congruent population genetic structuring, indicating that introgression changed the genetic make‐up of wild populations by increasing genetic diversity and reducing genetic divergence. However, the degree of genetic introgression varied among studied populations, being higher in the eastern part and lower in the western part of Estonia, which most likely reflects the history of past stocking activities. Using kernel smoothing and permutation testing, we detected considerable heterogeneity in introgression patterns across the genome, with a large number of regions exhibiting nonrandom introgression widely dispersed across the genome. We also observed substantial variation in nonrandom introgression patterns within populations, as the majority of genomic regions showing elevated or reduced introgression were not consistently detected among temporal samples. This suggests that recombination, selection and stochastic processes may contribute to complex nonrandom introgression patterns. Our results suggest that (i) some genomic regions in Atlantic salmon are more vulnerable to introgressive hybridization, while others show greater resistance to unidirectional gene flow; and (ii) the hybridization of previously separated populations leads to complex and dynamic nonrandom introgression patterns that most likely have functional consequences for indigenous populations.
Sarcoglyphis manipurensis sp. nov. (Orchidaceae) from Manipur, India
Authors: Kumar Vikas , Sharma Hidangmayum Bishwajit , Rao Abbareddy Nageswara
Published: February 2016

A new orchid species, viz. Sarcoglyphis manipurensis, is described and illustrated from Imphal east and Chandel districts of Manipur in northeast India. It's distinguishing characters and affinity with S. mirabilis (Rchb.f.) Garay is discussed. An updated artificial key to all known species of Sarcoglyphis is provided.
Characterization and correction of pressure drift in the ManoScan™ high‐resolution manometry system: In vitro and in vivo
Authors: Lamvik K. , Guiu Hernandez E. , Jones R. , Huckabee M.‐L.
Published: February 2016

Background

A substantial pressure drift in high‐resolution manometry (HRM) has been reported; however, fundamental questions remain regarding the origin and management of this drift. The aim of this study was to provide critical in‐depth analyses of ManoScan™ HRM drift in vitro and in vivo.

Methods

A total of sixteen 15‐min studies and twelve 5‐h studies were performed in a water bath at 37 °C at 4.0 cm depth (2.9 mmHg) with ESO and ESO Z catheters. Six 5‐h in vitro studies were performed similarly at a depth of 9.0 cm (6.6 mmHg). Eight 15‐min studies and nine 8‐h in vivo studies were performed with healthy participants. Two correction methods – thermal compensation (TC) and interpolated thermal compensation (ITC) – were tested.

Key Results

Overall pressure drift varied both between studies (p < 0.01) and within sensors (p < 0.01). Drift resulted from thermal shock, an initial pressure change at intubation, and baseline drift, a linear drift over time (R2 > 0.96). Contrary to previous reports, there was no correlation between drift and average (r = −0.02) or maximum pressure exposure (r = −0.05). Following data correction, ITC had the lowest median error but persisted with a maximum error of 2.5 mmHg (IQR = 3.0).

Conclusions & Inferences

The substantial drift in the ManoScan™ HRM system is highly variable and not corrected via the standard operating instructions. ITC has superior performance but requires communication with the manufacturer to enable this option. This has a substantial impact on clinical diagnosis, utility of existing normative data, and future research of HRM.
Diabetic gastroparesis alters the biomagnetic signature of the gastric slow wave
Authors: Bradshaw L. A. , Cheng L. K. , Chung E. , Obioha C. B. , Erickson J. C. , Gorman B. L. , Somarajan S. , Richards W. O.
Published: February 2016

Background

Gastroparesis is characterized by delayed gastric emptying without mechanical obstruction, but remains difficult to diagnose and distinguish from other gastrointestinal (GI) disorders. Gastroparesis affects the gastric slow wave, but non‐invasive assessment has been limited to the electrogastrogram (EGG), which reliably characterizes temporal dynamics but does not provide spatial information.

Methods

We measured gastric slow wave parameters from the EGG and magnetogastrogram (MGG) in patients with gastroparesis and in healthy controls. In addition to dominant frequency (DF) and percentage power distribution (PPD), we measured the propagation velocity from MGG spatiotemporal patterns and the percentage of slow wave coupling (%SWC) from EGG.

Key Results

No significant difference in DF was found between patients and controls. Gastroparesis patients had lower percentages of normogastric frequencies (60 ± 6% vs 78 ± 4%, p < 0.05), and higher brady (9 ± 2% vs 2 ± 1%, p < 0.05) and tachygastric (31 ± 2% vs 19 ± 1%, p < 0.05) frequency content postprandial, indicative of uncoupling. Propagation patterns were substantially different in patients and longitudinal propagation velocity was retrograde at 4.3 ± 2.9 mm/s vs anterograde at 7.4 ± 1.0 mm/s for controls (p < 0.01). No difference was found in %SWC from EGG.

Conclusions & Inferences

Gastric slow wave parameters obtained from MGG recordings distinguish gastroparesis patients from controls. Assessment of slow wave propagation may prove critical to characterization of underlying disease processes. Future studies should determine pathologic indicators from MGG associated with other functional gastric disorders, and whether multichannel EGG with appropriate signal processing also reveals pathology.
Cadmium toxicity investigated at the physiological and biophysical levels under environmentally relevant conditions using the aquatic model plant Ceratophyllum demersum
Authors: Andresen Elisa , Kappel Sophie , Stärk Hans‐Joachim , Riegger Ulrike , Borovec Jakub , Mattusch Jürgen , Heinz Andrea , Schmelzer Christian E. H. , Matoušková Šárka , Dickinson Bryan , Küpper Hendrik
Published: February 2016

Cadmium (Cd) is an important environmental pollutant and is poisonous to most organisms. We aimed to unravel the mechanisms of Cd toxicity in the model water plant Ceratophyllum demersum exposed to low (nM) concentrations of Cd as are present in nature.

Experiments were conducted under environmentally relevant conditions, including nature‐like light and temperature cycles, and a low biomass to water ratio. We measured chlorophyll (Chl) fluorescence kinetics, oxygen exchange, the concentrations of reactive oxygen species and pigments, metal binding to proteins, and the accumulation of starch and metals.

The inhibition threshold concentration for most parameters was 20 nM. Below this concentration, hardly any stress symptoms were observed. The first site of inhibition was photosynthetic light reactions (the maximal quantum yield of photosystem II (PSII) reaction centre measured as Fv/Fm, light‐acclimated PSII activity ΦPSII, and total Chl). Trimers of the PSII light‐harvesting complexes (LHCIIs) decreased more than LHC monomers and detection of Cd in the monomers suggested replacement of magnesium (Mg) by Cd in the Chl molecules. As a consequence of dysfunctional photosynthesis and energy dissipation, reactive oxygen species (superoxide and hydrogen peroxide) appeared.

Cadmium had negative effects on macrophytes at much lower concentrations than reported previously, emphasizing the importance of studies applying environmentally relevant conditions. A chain of inhibition events could be established.
Case Report of Lichen Planopilaris Occurring in a Pediatric Patient Receiving a Tumor Necrosis Factor α Inhibitor and a Review of the Literature
Authors: Jayasekera Prativa S.A. , Walsh Maeve L. , Hurrell Daniel , Parslew Richard A.G.
Published: February 2016

A 12‐year‐old girl with extended oligoarthritis treated with adalimumab presented with a short history of a progressive cutaneous eruption involving the legs and scalp. Physical examination and histologic results were consistent with lichen planopilaris. The adalimumab was discontinued. She received treatment with topical clobetasol propionate and the majority of the lesions resolved. Residual lesions and the extended oligoarthritis were then treated with sulfasalazine. Adalimumab is a tumor necrosis factor α (TNF‐α) inhibitor used for the treatment of a variety of immunologically mediated conditions, including lichen planus and lichen planopilaris. TNF‐α antagonists have been associated with paradoxical psoriasiform, lichenoid, eczematous, granulomatous, and acneiform eruptions. We detail this case and review the literature of lichenoid reactions secondary to TNF‐α inhibitors.
Congenital rubella syndrome with death from interstitial pneumonia
Authors: Mizuno Yoshifumi , Yokoi Kyoko , Suzuki Satoshi
Published: February 2016

There was a rubella epidemic in Japan in 2012–2013, which led to an increased number infants being born with congenital rubella syndrome (CRS). Symptoms of CRS are varied and include cataracts, congenital heart disease, and hearing impairment, but case reports of CRS complicated by interstitial pneumonia are rare. We report the case of a patient with CRS who died of respiratory failure caused by interstitial pneumonia. Thrombocytopenia had been present for approximately 1 month after birth, and the patient presented with sudden lung hemorrhage at 64 days old. Thereafter, respiratory condition deteriorated, and the patient died at 107 days old. Given that infants with CRS who have thrombocytopenia and interstitial pneumonia have a high risk of death, they should be monitored carefully for potential complications.
Administration of G‐CSF from day +6 post‐allogeneic hematopoietic stem cell transplantation in children and adolescents accelerates neutrophil engraftment but does not appear to have an impact on cost savings
Authors: O'Rafferty Ciara , O'Brien Mairead , Smyth Elaine , Keane Sinead , Robinson Hillary , Lynam Paul , O'Marcaigh Aengus , Smith Owen P.
Published: February 2016

G‐CSF post‐allogeneic HSCT accelerates neutrophil engraftment, but evidence that it impacts on cost‐related outcomes is lacking. We performed a retrospective child and adolescent single‐center cohort study examining G‐CSF administration from Day +6 of allogeneic HSCT vs. ad hoc G‐CSF use where clinically indicated. Forty consecutive children and adolescents undergoing allogeneic HSCT were included. End‐points were as follows: time to engraftment; incidence of acute and chronic GvHD; number of patients alive at Day +100; 180‐day TRM; post‐transplant days in hospital; and cost of antimicrobials, TPN, and G‐CSF usage. Neutrophil engraftment occurred earlier in the group that received G‐CSF from Day +6. There was no difference between groups in any of the other end‐points with the following exception: the cost of GCSF was significantly higher in the D + 6 G‐CSF group. However, median G‐CSF cost in this group amounted to only €280. There was a trend towards reduced cost of antimicrobials in the D + 6 G‐CSF group, although this did not reach significance (p = 0.13). The median cost per patient of antimicrobial agents between groups differed by €1116. This study demonstrated the administration of G‐CSF on Day +6 in pediatric HSCT to be safe. A further study using a larger cohort of patients is warranted to ascertain its true clinico‐economic value.
Deconstructing the Gains from Trade: Selection of Industries vs Reallocation of Workers
Authors: Bolatto Stefano , Sbracia Massimo
Published: February 2016

In a Ricardian model with general distributions of industry efficiencies, the welfare gains from trade can be decomposed into a selection and a reallocation effect. The former is the change in average efficiency as a result of the selection of industries that survive international competition. The latter is the rise in the weight of exporting industries in production, owing to the reallocation of workers from non‐exporting industries. This decomposition, which is hard to calculate in the general case, simplifies dramatically with Fréchet‐distributed efficiencies, providing easy‐to‐quantify model‐based measures of these two effects. Selection (reallocation) turns out to matter mostly when welfare gains are small (large).
Pre‐transplant soluble CD30 in combination with total DSA but not pre‐transplant C1q‐DSA predicts antibody‐mediated graft loss in presensitized high‐risk kidney transplant recipients
Authors: Schaefer S. M. , Süsal C. , Opelz G. , Döhler B. , Becker L. E. , Klein K. , Sickmüller S. , Waldherr R. , Macher‐Goeppinger S. , Schemmer P. , Beimler J. , Zeier M. , Morath C.
Published: February 2016

Presensitized kidney transplant recipients are at high‐risk for early antibody‐mediated rejection. We studied the impact of pre‐ and post‐transplant donor‐specific human leukocyte antigen (HLA) antibodies (DSA) and T‐cell‐activation on the occurrence of antibody‐mediated rejection episodes (AMR) and graft loss (AMR‐GL) in a unique cohort of 80 desensitized high‐risk kidney transplant recipients. Patients with pre‐transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR‐GL. The rates of AMR and AMR‐GL were not significantly increased in patients with complement split product (C1q)‐binding pre‐transplant DSA. Pre‐transplant C1q‐DSA became undetectable post‐transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR‐GL. In contrast, the post‐transplant presence of C1q‐DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR‐GL (86 vs 0 vs 0%; log‐rank P < 0.001) compared with post‐transplant DSA without C1q‐binding or the absence of DSA. Patients with both pre‐transplant DSA and evidence of pre‐transplant T‐cell‐activation as indicated by soluble CD30‐positivity showed a significantly increased risk for AMR‐GL [HR = 11.1, 95% confidence interval (CI) = 1.68–73.4; log‐rank P = 0.013]. In these high‐risk patients, AMR‐GL was associated with total DSA in combination with T‐cell‐activation pre‐transplant, and de novo or persistent C1q‐binding DSA post‐transplant.
What is wrong with the regulatory T cells and foetomaternal tolerance in women with recurrent miscarriages?
Authors: Craenmehr M. H. C. , Heidt S. , Eikmans M. , Claas F. H. J.
Published: February 2016

Couples of whom the woman has had a miscarriage have two major concerns: the cause and possible risk of recurrence. Unfortunately, a significant proportion of cases of recurrent miscarriage (RM) remain unexplained despite detailed investigation. Because data suggest that regulatory T cells (Treg) are involved in the maternal acceptance of the allogeneic foetus, RM could possibly be explained by a disturbance of the Treg network. The possible role of Tregs in RM is described in this review, as well as their potential application in diagnostics and therapeutic intervention trials.
Use of n‐of‐1 (single patient) trials to assess the effect of age of transfused blood on health‐related quality of life in transfusion‐dependent patients
Authors: Hsia Cyrus C. , Mahon Jeffrey L. , Seitelbach Maayan , Chia Justin , Zou Guangyong , Chin‐Yee Ian H.
Published: February 2016

BACKGROUND

The impact of age of red blood cells on health‐related quality of life (HRQL) in patients who require chronic transfusions is not known. We assessed this using n‐of‐1 trials in patient populations where large randomized trials have not been done to date.

STUDY DESIGN AND METHODS

Chronically transfusion‐dependent adult patients were randomly assigned over time to four fresh (<7 days of storage) and four standard‐issue (up to 42 days of storage) blood transfusions in prospective double‐blinded multicrossover studies (n‐of‐1 trials). HRQL questionnaires were completed before and at 24 hours after each transfusion. Hemoglobin (Hb) levels were measured before each subsequent transfusion.

RESULTS

Twenty transfusion‐dependent patients were enrolled, of whom nine (five myelodysplastic syndromes, two myelofibrosis, one β‐thalassemia major, one Diamond‐Blackfan anemia) completed at least six transfusions. Mean ages of fresh and standard‐issue blood transfused were 4.0 and 23.2 days, respectively. There were no significant differences in the effect of standard and fresh blood on follow‐up Hb levels or the eight HRQL dimensions assessed in all analyses.

CONCLUSIONS

In chronically transfused patients, there were no significant differences in HRQL or Hb levels between fresh versus standard blood. While larger trials are needed, these results support current practices in hospital blood transfusion laboratories using a first‐in, first‐out model of blood utilization for these transfusion‐dependent patients. Use of n‐of‐1 trials to determine the benefits of transfusions in single patients appears to be feasible.
Efficacy and safety of electrochemotherapy combined with peritumoral IL‐12 gene electrotransfer of canine mast cell tumours
Authors: Cemazar M. , Ambrozic Avgustin J. , Pavlin D. , Sersa G. , Poli A. , Krhac Levacic A. , Tesic N. , Lampreht Tratar U. , Rak M. , Tozon N.
Published: February 2016

Electrochemotherapy combined with peritumoral interleukin‐12 (IL‐12) gene electrotransfer was used for treatment of mast cell tumours in 18 client‐owned dogs. Local tumour control, recurrence rate, as well as safety of combined therapy were evaluated. One month after the therapy, no side effects were recorded and good local tumour control was observed with high complete responses rate which even increased during the observation period to 72%. IL‐12 gene electrotransfer resulted in 78% of patients with detectable serum IFN‐γ and/or IL‐12 levels. In the treated tumours vascular changes as well as minimal T‐lymphocytes infiltration was observed. After 1 week, the plasmid DNA was not detected intra‐ or peritumorally and no horizontal gene transfer was observed. In summary, our study demonstrates high antitumour efficacy of electrochemotherapy combined with IL‐12 electrotransfer, which also prevented recurrences or distant metastases, as well as its safety and feasibility in treatment of canine mast cell tumours.