bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating marker‐guided treatment selection strategies
Authors: Matsouaka Roland A. , Li Junlong , Cai Tianxi
Published: April 2014

A potential venue to improve healthcare efficiency is to effectively tailor individualized treatment strategies by incorporating patient level predictor information such as environmental exposure, biological, and genetic marker measurements. Many useful statistical methods for deriving individualized treatment rules (ITR) have become available in recent years. Prior to adopting any ITR in clinical practice, it is crucial to evaluate its value in improving patient outcomes. Existing methods for quantifying such values mainly consider either a single marker or semi‐parametric methods that are subject to bias under model misspecification. In this article, we consider a general setting with multiple markers and propose a two‐step robust method to derive ITRs and evaluate their values. We also propose procedures for comparing different ITRs, which can be used to quantify the incremental value of new markers in improving treatment selection. While working models are used in step I to approximate optimal ITRs, we add a layer of calibration to guard against model misspecification and further assess the value of the ITR non‐parametrically, which ensures the validity of the inference. To account for the sampling variability of the estimated rules and their corresponding values, we propose a resampling procedure to provide valid confidence intervals for the value functions as well as for the incremental value of new markers for treatment selection. Our proposals are examined through extensive simulation studies and illustrated with the data from a clinical trial that studies the effects of two drug combinations on HIV‐1 infected patients.
Peripheral blood cells chimerism after unrelated cord blood transplantation in children: kinetics, predictive factors and impact on post‐transplant outcome
Authors: Elkaim Elodie , Picard Christophe , Galambrun Claire , Barlogis Vincent , Loundou Anderson , Curtillet Catherine , Oudin Claire , Thuret Isabelle , Chambost Hervé , Michel Gérard
Published: April 2014

This study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99·9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post‐transplant outcome. Ninety‐four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post‐transplant dates, using a real‐time polymerase chain reaction method with 0·1% sensitivity. Cumulative incidence of cDC at 1 year post‐transplantation was 61·8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0·03), older age (above 2·16 years, the first quartile of age, P = 0·0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5‐6/6, P < 0·001) increased the probability of post‐transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99·9% donor chimerism on days 15–30 post‐transplant) appeared useful to predict engraftment (P = 0·003) as well as acute and chronic graft‐versus‐host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ≤99·9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT.
Bleaching of the post‐IR IRSL signal: new insights for feldspar luminescence dating
Authors: Kars Romée H. , Reimann Tony , Ankjærgaard Christina , Wallinga Jakob
Published: April 2014

Post‐infrared (pIR) stimulated luminescence dating of sedimentary feldspar largely avoids the effects of anomalous fading that affect conventional infrared stimulated luminescence (IRSL) dating. However, optical resetting of pIR signals is more difficult than resetting the conventional IRSL signal, which may undermine the crucial assumption that pIR signals were effectively bleached upon deposition and burial of sediment grains. In this study, we quantify the bleaching properties of several pIR signals on various samples using laboratory‐simulated bleaching in full sunlight and water‐attenuated sunlight. Our data show that bleaching is most efficient under full spectrum conditions for all pIR signals and that pIR signals measured at elevated temperature are increasingly harder to bleach than IR and pIR signals measured at low temperature (e.g. IR at 50°C). All bleaching curves exhibit a very slow and steady decrease, indicating that a fixed un‐bleachable residual level cannot be reached within the 11 days of solar simulator exposure undertaken here. We show that the magnitude of a laboratory‐determined residual dose depends on the adopted bleaching protocol and cannot be used as a proxy for the dose that remains in the sample at the time of burial (remnant dose). Our data emphasize the importance of finding a balance between sufficient signal stability and a minimized contribution of a remnant dose when using pIR procedures for feldspar luminescence dating.
Mapping the Trajectory of Socioeconomic Disparity in Working Memory: Parental and Neighborhood Factors
Authors: Hackman Daniel A. , Betancourt Laura M. , Gallop Robert , Romer Daniel , Brodsky Nancy L. , Hurt Hallam , Farah Martha J.
Published: April 2014

Working memory (WM) is positively correlated with socioeconomic status (SES). It is not clear, however, if SES predicts the rate of WM development over time or whether SES effects are specific to family rather than neighborhood SES. A community sample of children (n = 316) enrolled between ages 10 and 13 completed four annual assessments of WM. Lower parental education, but not neighborhood disadvantage, was associated with worse WM performance. Neither measure of SES was associated with the rate of developmental change. Consequently, the SES disparity in WM is not a developmental lag that narrows or an accumulating effect that becomes more pronounced. Rather, the relation between family SES and WM originates earlier in childhood and is stable through adolescence.
The Impact of Neighborhood, Family, and Individual Risk Factors on Toddlers’ Disruptive Behavior
Authors: Heberle Amy E. , Thomas Yolanda M. , Wagmiller Robert L. , Briggs‐Gowan Margaret J. , Carter Alice S.
Published: April 2014

Disadvantaged neighborhoods confer risk for behavior problems in school‐aged children but their impact in toddlerhood is unknown. Relations between toddlers’ disruptive behavior and neighborhood disadvantage, family disadvantage, violence or conflict exposure, parent depressive symptoms, and parenting behavior were examined using multilevel, multigroup (girl–boy) models. Participants were 1,204 families (mean child age = 24.7 months). Unique associations between disruptive behavior and all risk factors were observed, but the effect of neighborhood disadvantage was negligible when all of the more proximal factors were accounted for. The results suggest both that children in disadvantaged neighborhoods are at greater risk of behavior problems than children in nondisadvantaged neighborhoods and that optimal prevention/intervention work with these children will attend to proximal risk factors.
Conversation and Object Manipulation Influence Children's Learning in a Museum
Authors: Jant Erin A. , Haden Catherine A. , Uttal David H. , Babcock Elizabeth
Published: April 2014

The effects of parent–child conversation and object manipulation on children's learning, transfer of knowledge, and memory were examined in two museum exhibits and conversations recorded at home. Seventy‐eight children (Mage = 4.9) and their parents were randomly assigned to receive conversation cards featuring elaborative questions about exhibit objects, the physical objects themselves, both, or neither, before their exhibit visits. Dyads who received the cards engaged in more elaborative talk and joint nonverbal activities with objects in the first exhibit than those who did not. Dyads who received objects engaged in the most parent–child joint talk. Results also illustrate transfer of information across exhibits and from museum to home. Implications for understanding mechanisms of informal learning and transfer are discussed.
Do Children Who Experience Regret Make Better Decisions? A Developmental Study of the Behavioral Consequences of Regret
Authors: O'Connor Eimear , McCormack Teresa , Feeney Aidan
Published: April 2014

Although regret is assumed to facilitate good decision making, there is little research directly addressing this assumption. Four experiments (N = 326) examined the relation between children's ability to experience regret and the quality of their subsequent decision making. In Experiment 1 regret and adaptive decision making showed the same developmental profile, with both first appearing at about 7 years. In Experiments 2a and 2b, children aged 6–7 who experienced regret decided adaptively more often than children who did not experience regret, and this held even when controlling for age and verbal ability. Experiment 3 ruled out a memory‐based interpretation of these findings. These findings suggest that the experience of regret facilitates children's ability to learn rapidly from bad outcomes.
Prospective cohort study on change in weight status and occurrence of habitual snoring in children
Authors: Anuntaseree W. , Sangsupawanich P. , Mo‐suwan L. , Ruangnapa K. , Pruphetkaew N.
Published: April 2014

Objective

To determine the association between the change in weight status and newly developed snoring in children.

Design

This was a prospective cohort study.

Setting

Structured interviews were conducted at participants' homes, and physical examinations were performed at The‐pa Community Hospital in Southern Thailand.

Participants

Cohort subjects (n = 1076) were recruited from children born over a 1‐year period between November 2000 and October 2001 in The‐pa District of Songkhla Province, Southern Thailand. Data collection was performed when the child was 5 and 8.5 years old.

Main outcome measures

The child's snoring, weight, height and tonsillar size were examined. The change in weight status was categorised into four groups: not obese, became not obese, became obese and persistently obese.

Results

Of 1076, 983 subjects (91.4%) completed both surveys. The overall prevalence of habitual snoring decreased from 13% at age 5 to 10.9% at age 8.5 years. Of the 855 children who reported not snoring in the first survey, 61 (7.1%) had become habitual snorers. After adjusting for tonsillar size, children who had become obese or were persistently obese had a significant association with becoming a new snorer with an odds ratio of 5.8 (Confidence interval, CI, 1.3–25.8) and 11.7 (CI, 2.5–54.9), respectively.

Conclusions

Children with newly developed obesity at 8.5 years old were strongly associated with new snoring occurrence, which is similar to the findings of long‐term follow‐up studies in adults. Our findings support the idea that the patterns of changes in weight status and snoring development in adults begin as early as the primary school years.
The Complementary Niches of Anthropocentric and Biocentric Conservationists
Authors: HUNTER MALCOLM L. , REDFORD KENT H. , LINDENMAYER DAVID B.
Published: April 2014

A divergence of values has become apparent in recent debates between conservationists who focus on ecosystem services that can improve human well‐being and those who focus on avoiding the extinction of species. These divergent points of view fall along a continuum from anthropocentric to biocentric values, but most conservationists are relatively closer to each other than to the ends of the spectrum. We have some concerns with both positions but emphasize that conservation for both people and all other species will be most effective if conservationists focus on articulating the values they all share, being respectful of divergent values, and collaborating on common interests. The conservation arena is large enough to accommodate many people and organizations whose diverse values lead them to different niches that can, with good will and foresight, be far more complementary than competitive.

Los Nichos Complementarios de los Conservacionistas Antropocéntricos y Biocéntricos
Defining the Impact of Non‐Native Species
Authors: JESCHKE JONATHAN M. , BACHER SVEN , BLACKBURN TIM M. , DICK JAIMIE T. A. , ESSL FRANZ , EVANS THOMAS , GAERTNER MIRIJAM , HULME PHILIP E. , KÜHN INGOLF , MRUGAŁA AGATA , PERGL JAN , PYŠEK PETR , RABITSCH WOLFGANG , RICCIARDI ANTHONY , RICHARDSON DAVID M. , SENDEK AGNIESZKA , VILÀ MONTSERRAT , WINTER MARTEN , KUMSCHICK SABRINA
Published: April 2014

Non‐native species cause changes in the ecosystems to which they are introduced. These changes, or some of them, are usually termed impacts; they can be manifold and potentially damaging to ecosystems and biodiversity. However, the impacts of most non‐native species are poorly understood, and a synthesis of available information is being hindered because authors often do not clearly define impact. We argue that explicitly defining the impact of non‐native species will promote progress toward a better understanding of the implications of changes to biodiversity and ecosystems caused by non‐native species; help disentangle which aspects of scientific debates about non‐native species are due to disparate definitions and which represent true scientific discord; and improve communication between scientists from different research disciplines and between scientists, managers, and policy makers. For these reasons and based on examples from the literature, we devised seven key questions that fall into 4 categories: directionality, classification and measurement, ecological or socio‐economic changes, and scale. These questions should help in formulating clear and practical definitions of impact to suit specific scientific, stakeholder, or legislative contexts.

Definiendo el Impacto de las Especies No‐Nativas
On Uncertain Sightings and Inference about Extinction
Authors: SOLOW ANDREW R. , BEET ANDREW R.
Published: April 2014

The extinction of many species can only be inferred from the record of sightings of individuals. Solow et al. (2012, Uncertain sightings and the extinction of the Ivory‐billed Woodpecker. Conservation Biology 26:180–184) describe a Bayesian approach to such inference and apply it to a sighting record of the Ivory‐billed Woodpecker (Campephilus principalis). A feature of this sighting record is that all uncertain sightings occurred after the most recent certain sighting. However, this appears to be an artifact. We extended this earlier work in 2 ways. First, we allowed for overlap in time between certain and uncertain sightings. Second, we considered 2 plausible statistical models of a sighting record. In one of these models, certain and uncertain sightings that are valid arise from the same process whereas in the other they arise from independent processes. We applied both models to the case of the Ivory‐billed Woodpecker. The result from the first model did not favor extinction, whereas the result for the second model did. This underscores the importance, in applying tests for extinction, of understanding what could be called the natural history of the sighting record.

Sobre Avistamientos Inciertos e Inferencia de la Extinción
Assessing Multiregion Avian Benefits from Strategically Targeted Agricultural Buffers
Authors: EVANS KRISTINE O. , BURGER L. WES , RIFFELL SAM , SMITH MARK D.
Published: April 2014

Mounting evidence of wildlife population gains from targeted conservation practices has prompted the need to develop and evaluate practices that are integrated into production agriculture systems and targeted toward specific habitat objectives. However, effectiveness of targeted conservation actions across broader landscapes is poorly understood. We evaluated multiregion, multispecies avian densities on row‐crop fields with native grass field margins (i.e., buffers) as part of the first U.S. agricultural conservation practice designed to support habitat and population recovery objectives of a national wildlife conservation initiative. We coordinated breeding season point transect surveys for 6 grassland bird species on 1151 row‐crop fields with and without native grass buffers (9–37 m) in 14 U.S. states (10 ecoregions) from 2006 to 2011. In most regions, breeding season densities of 5 of 6 targeted bird species were greater in the 500‐m surrounding survey points centered on fields with native grass buffers than in landscapes without buffers. Relative effect sizes were greatest for Northern Bobwhite (Colinus virginianus), Dickcissel (Spiza americana), and Field Sparrow (Spizella pusilla) in the Mississippi Alluvial Valley and Eastern Tallgrass Prairie regions. Other species (e.g., Eastern Meadowlark [Sturnella magna], Grasshopper Sparrow [Ammodramus savannarum]) exhibited inconsistent relative effect sizes. Bird densities on fields with and without buffers were greatest in the Central Mixed‐grass Prairie region. Our results suggest that strategic use of conservation buffers in regions with the greatest potential for relative density increases in target species will elicit greater range‐wide population response than diffuse, uninformed, and broadly distributed implementation of buffers. We recommend integrating multiple conservation practices in broader agricultural landscapes to maximize conservation effectiveness for a larger suite of species.

Evaluación de los Beneficios de la Mutliregionalidad de Aves a Partir de Amortiguadores Agriculturales Estratégicamente Señalados
Extracorporeal membrane oxygenation: experience in acute graft failure after heart transplantation
Authors: Lehmann Sven , Uhlemann Madlen , Etz Christian D. , Garbade Jens , Schroeter Thomas , Borger Michael , Misfeld Martin , Bittner Hartmuth B. , Mohr Friedrich Wilhelm
Published: April 2014

Introduction

Acute graft failure is the leading cause of early mortality after heart transplantation (HTx). Extracorporeal membrane oxygenation (ECMO) is an efficient therapeutic option to treat various pathologies, unburden the left and right ventricle, and allow for functional recovery of the transplanted heart. We reviewed our ECMO experience and outcomes in HTx patients.

Methods

Retrospectively, we analyzed all patients who received an orthotopic HTx (n = 298) in our department over a 15‐yr period (1997 through 2011) to assess the incidence of post‐HTx ECMO implantation, perioperative complications, early and one‐yr mortality as well as causes of death.

Results

ECMO therapy was utilized to treat graft failure in 28 patients (10.6%) with a mean duration of ECMO support of 4.2 d (six h to 9.4 d). Multivariate analysis revealed as independent predictors for mortality low cardiac output (p = 0.028; odds ratio (OR) = 11.3) and stroke (p = 0.008; OR = 19.7). Cumulative survival rates were 46.4 ± 9.4% within 30 d and 25.0 ± 8.2% at one yr. Causes of death were multiorgan failure (n = 9), sepsis (n = 9), lung failure (n = 2), and intracerebral bleeding (n = 2). ECMO was implanted due to primary graft failure (PGF, n = 16), sepsis (n = 4), and right heart failure (n = 6).

Conclusion

Temporary ECMO support for postoperative output failure is an acceptable option as a last resort for otherwise doomed patients with fatal graft failure after HTx. The small fraction of patients surviving appear to have a decent long‐term prognosis.
Developmental trajectories of receptive and expressive communication in children and young adults with cerebral palsy
Authors: Vos Rimke C , Dallmeijer Annet J , Verhoef Marjolein , Van Schie Petra E M , Voorman Jeanine M , Wiegerink Diana J H G , Geytenbeek Joke J M , Roebroeck Marij E , Becher Jules G ,   the PERRIN+ Study Group
Published: April 2014

Aim

The aim of this study was to determine the developmental trajectories of expressive (speech) and receptive (spoken and written language) communication by type of motor disorder and intellectual disability in individuals with cerebral palsy (CP).

Method

The development of 418 participants (261 males, 157 females; mean age 9y 6mo [SD 6y 2mo], range 1–24y; Gross Motor Function Classification System (GMFCS) level I [n=206], II [n=57], III [n=59], IV [n=54], V [n=42]) was followed for 2 to 4 years in a longitudinal study. Communication performance was measured using the Vineland Adaptive Behavior Scales. The type of motor disorder was differentiated by type of CP as unilateral spastic (USCP, n=161), bilateral spastic (BSCP, n=202), and non‐spastic (NSCP, n=55), while intellectual disability was determined by IQ or school type (regular or special). A multilevel analysis was then used to model the developmental trajectories.

Results

The most favourable development of expressive communication was seen in USCP (vs BSCP β [SE]‐2.74 [1.06], NSCP β [SE]‐2.67 [1.44]). The difference between the development trajectory levels of children with and without intellectual disability was smaller for children with USCP than for those with BSCP and NSCP. For receptive communication, the most favourable development was found for all children with USCP and for BSCP or NSCP without intellectual disability (vs intellectual disability β [SE]‐4.00 [1.16]). Development of written language was most favourable for children without intellectual disability (vs intellectual disability β [SE]‐23.11 [2.85]).

Interpretation

The development of expressive communication was found to be most closely related to type of motor disorder, whereas the development of receptive communication was found to be most closely related to intellectual disability.
The influence of sex on renal function decline in people with Type 2 diabetes
Authors: de Hauteclocque A. , Ragot S. , Slaoui Y. , Gand E. , Miot A. , Sosner P. , Halimi J.‐M. , Zaoui P. , Rigalleau V. , Roussel R. , Saulnier P.‐J. , Hadjadj Samy S. ,   The SURDIAGENE Study group
Published: April 2014

Aims

Several reports have suggested a relationship between male sex and albuminuria in Type 2 diabetes, but impact on renal function decline has not been established. Our aim was to describe the influence of sex on renal function decline in Type 2 diabetes.

Methods

SURDIAGENE, an inception cohort, consisted in 1470 people with Type 2 diabetes. Patients without renal replacement therapy and with ≥ 3 serum creatinine determinations during follow‐up prior to end‐stage renal disease were included in the study. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Primary outcome was steep estimated glomerular filtration rate (eGFR) decline, defined as a yearly slope value lower than –3.5 ml min−1 1.73 m−2. Secondary outcomes were estimated glomerular filtration rate trajectories according to sex and occurrence of end‐stage renal disease.

Results

A total of 22 914 serum creatinine determinations were considered in 1146 participants (60% men), aged 65 ± 11 years, with a median follow‐up duration of 5.7 years (range 0.1–10.2). Median yearly estimated glomerular filtration rate slope was –1.31 ml min−1 1.73 m−2 in women and –1.77 ml min−1 1.73 m−2 in men (P < 0.001). Men were more likely than women to develop end‐stage renal disease (22 men vs. 7 women; Plog‐rank = 0.03). Male sex was an independent risk factor of steep estimated glomerular filtration rate decline [adjusted odds ratio = 1.33 (1.02–1.76), P = 0.04] after adjustment for age, time from diagnosis of Type 2 diabetes, glycated haemoglobin, systolic blood pressure and urinary albumin:creatinine ratio. A multivariable linear mixed‐effects model showed a significant difference of estimated glomerular filtration rate trajectories between men and women (P < 0.001).

Conclusion

Male sex is an important independent factor associated with renal function decline in Type 2 diabetes.
Residential traffic and incidence of Type 2 diabetes: the German Health Interview and Examination Surveys
Authors: Heidemann C. , Niemann H. , Paprott R. , Du Y. , Rathmann W. , Scheidt‐Nave C.
Published: April 2014

Aims

To investigate whether an indicator of overall traffic intensity is related to the risk of Type 2 diabetes in a nationwide cohort.

Methods

The study population comprised 3604 adults aged 18–79 years and without diabetes from the German National Health Interview and Examination Survey (GNHIES98, 1997–1999) who participated again in a follow‐up survey (DEGS1, 2008–2011). The association between the participants' reported traffic intensity at their residential address and Type 2 diabetes incidence was examined using logistic regression models.

Results

During a mean of 12.1 years of follow‐up, 252 of the participants included in the study developed Type 2 diabetes. Compared with people living in traffic‐calmed areas, odds ratios were 1.15 (95% CI 0.80–1.67) for people living on moderately busy side streets, 1.11 (95% CI 0.69–1.80) for people living on considerably busy side streets, 1.41 (95% CI 0.96–2.08) for people living on heavily busy roads, and 1.97 (95% CI 1.07–3.64) for people living on extremely busy roads, after adjusting for age, sex, active and passive smoking, type of heating, education, BMI, waist circumference, sport activity and parental diabetes history.

Conclusions

The twofold higher risk of Type 2 diabetes observed for people exposed to intense traffic in this nationwide cohort extends the limited evidence from previous selected populations. Although the underlying traffic‐related components and their biological mechanisms still need to be unravelled, traffic exposure control should be considered in public health strategies to reduce the global burden of diabetes.
Effects of an inpatient rehabilitation program after temporal lobe epilepsy surgery and other factors on employment 2 years after epilepsy surgery
Authors: Thorbecke Rupprecht , May Theodor W. , Koch‐Stoecker Steffi , Ebner Alois , Bien Christian G. , Specht Ulrich
Published: April 2014

Objective

To evaluate the effects of a postsurgical rehabilitation program on employment status 2 years after temporal lobe epilepsy surgery in relation to other predictors.

Methods

Employment outcome 2 years after temporal lobe resection in a group of 232 adult patients with the offer of a 3‐week inpatient rehabilitation program immediately after surgery (“Reha group”) was compared to a group of 119 patients who had surgery before such a rehabilitation program existed. One hundred thirty‐nine (59.9%) of the Reha group patients attended the rehabilitation program. Further predictors for employment outcome were analyzed using multivariate logistic regression analysis.

Results

Preoperatively, the groups did not differ significantly in variables relevant for employment, including employment rate. Two years after surgery, the rate of those not being employed had decreased in the Reha group from 38.4% to 27.6% (p < 0.001, McNemar test), and slightly increased in the control group (37.8–42.0%; n.s.), resulting in a difference of 14.4% in favor of the Reha group (p = 0.008). General unemployment rates during the two observation periods were similar. In addition to the offer of rehabilitation support (“Reha group”) and preoperative employment, the following other variables were shown as significant predictors of employment post surgery in multivariate regression analysis: seizure outcome, diagnosis of a personality disorder preoperatively, and age at surgery (all, p < 0.01; Nagelkerkes R2 = 0.59).

Significance

Independently from other factors, a 3‐week inpatient rehabilitation program after temporal lobe epilepsy surgery seems to improve employment status 2 years after surgery.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Recurrent generalized seizures, visual loss, and palinopsia as phenotypic features of neuronal ceroid lipofuscinosis due to progranulin gene mutation
Authors: Canafoglia Laura , Morbin Michela , Scaioli Vidmer , Pareyson Davide , D'Incerti Ludovico , Fugnanesi Valeria , Tagliavini Fabrizio , Berkovic Samuel F. , Franceschetti Silvana
Published: April 2014

We detail the phenotype of a novel form of neuronal ceroid lipofuscinosis due to a homozygous progranulin gene mutation (c.813_816del; CLN11 MIM #614706). The symptoms appeared in two young adult siblings, and included progressive retinopathy, recurrent generalized seizures, moderate ataxia, and subtle cognitive dysfunction. Long‐lasting episodes of palinopsia were a recurring symptom and associated with polyphasic visual‐evoked potential waveform that suggested hyperexcitability of the occipital cortex. Electroencephalography showed rare spike‐wave paroxysms, and magnetic resonance imaging revealed selective cerebellar atrophy. Skin biopsy revealed fingerprint storage and the absence of progranulin protein. Electron microscopy of peripheral blood leukocytes showed fingerprint profiles in 1/100 lymphocytes. These findings define a novel phenotype and provide clues for better understanding of progranulin function.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Role of integrin signalling through integrin‐linked kinase in skin physiology and pathology
Authors: Eckes Beate , Krieg Thomas , Wickström Sara A.
Published: April 2014

Cell–matrix adhesions provide structural stability to the tissue and regulate intracellular signalling pathways that are important for cell fate decisions of the different cell populations within the skin. As a consequence of these central functions, genetic or functional impairment of various key protein components of matrix adhesions plays a causative role in the aetiology or pathophysiology in a large variety of skin disorders. Research towards understanding the molecular composition of these adhesions as well as the mechanisms by which they transmit signals is therefore of obvious importance. In this essay, we discuss the roles of integrin‐linked kinase, a key component of cell–matrix adhesions, in the (patho)physiology of skin and in particular highlight its role in regulating mechanical tension and matrix remodelling both in the epidermis and in the dermis.
YB‐1 promotes transcription of cyclin D1 in human non‐small‐cell lung cancers
Authors: Harada Masanori , Kotake Yojiro , Ohhata Tatsuya , Kitagawa Kyoko , Niida Hiroyuki , Matsuura Shun , Funai Kazuhito , Sugimura Haruhiko , Suda Takafumi , Kitagawa Masatoshi
Published: April 2014

Cyclin D1, an oncogenic G1 cyclin, and YB‐1, a transcription factor involved in cell growth, are both over‐expressed in several human cancers. In human lung cancer, the functional association between YB‐1 and cyclin D1 has never been elucidated. In this study, we show YB‐1 is involved in the transcription of cyclin D1 in human lung cancer. Depletion of endogenous YB‐1 by siRNA inhibited progression of G1 phase and down‐regulated both the protein and mRNA levels of cyclin D1 in human lung cancer cells. Forced over‐expression of YB‐1 with a cyclin D1 reporter plasmid increased luciferase activity, and ChIP assay results showed YB‐1 bound to the cyclin D1 promoter. Moreover, the amount of YB‐1 mRNA positively correlated with cyclin D1 mRNA levels in clinical non‐small‐cell lung cancer (NSCLC) specimens. Immunohistochemical analysis also indicated YB‐1 expression correlated with cyclin D1 expression in NSCLC specimens. In addition, most of the cases expressing both cyclin D1 and CDC6, another molecule controlled by YB‐1, had co‐existing YB‐1 over‐expression. Together, our results suggest that aberrant expression of both cyclin D1 and CDC6 by YB‐1 over‐expression may collaboratively participate in lung carcinogenesis.
Schizosaccharomyces pombe centromere protein Mis19 links Mis16 and Mis18 to recruit CENP‐A through interacting with NMD factors and the SWI/SNF complex
Authors: Hayashi Takeshi , Ebe Masahiro , Nagao Koji , Kokubu Aya , Sajiki Kenichi , Yanagida Mitsuhiro
Published: April 2014

CENP‐A is a centromere‐specific variant of histone H3 that is required for accurate chromosome segregation. The fission yeast Schizosaccharomyces pombe and mammalian Mis16 and Mis18 form a complex essential for CENP‐A recruitment to centromeres. It is unclear, however, how the Mis16‐Mis18 complex achieves this function. Here, we identified, by mass spectrometry, novel fission yeast centromere proteins Mis19 and Mis20 that directly interact with Mis16 and Mis18. Like Mis18, Mis19 and Mis20 are localized at the centromeres during interphase, but not in mitosis. Inactivation of Mis19 in a newly isolated temperature‐sensitive mutant resulted in CENP‐A delocalization and massive chromosome missegregation, whereas Mis20 was dispensable for proper chromosome segregation. Mis19 might be a bridge component for Mis16 and Mis18. We isolated extragenic suppressor mutants for temperature‐sensitive mis18 and mis19 mutants and used whole‐genome sequencing to determine the mutated sites. We identified two groups of loss‐of‐function suppressor mutations in non‐sense‐mediated mRNA decay factors (upf2 and ebs1), and in SWI/SNF chromatin‐remodeling components (snf5, snf22 and sol1). Our results suggest that the Mis16‐Mis18‐Mis19‐Mis20 CENP‐A‐recruiting complex, which is functional in the G1‐S phase, may be counteracted by the SWI/SNF chromatin‐remodeling complex and non‐sense‐mediated mRNA decay, which may prevent CENP‐A deposition at the centromere.
Gendered Constructions of Leadership in Danish Job Advertisements
Authors: Askehave Inger , Zethsen Karen Korning
Published: April 2014

The purpose of this article is to consider the gender imbalance at top management level from a discourse analytical perspective. More specifically, it investigates the language of 39 Danish top executive job advertisements and considers which leadership identities are projected as desirable or necessary. This is done by carrying out two interlinked studies: a semantic field analysis of the sections in the job advertisements describing the leadership traits of the ideal candidate (Study 1) and a study of MBA students' responses to extracts from the advertisements as far as gender is concerned (Study 2). Semantic field analysis reveals that all the job advertisements are gender‐biased and that most traits described in the advertisements are associated with traditional or stereotypical masculine attributes. Study 2 confirms this finding, as respondents (MBA students) assign a masculine identity to the vast majority of the extracts from the job advertisements.
Comparative study of Hsp27, GSK3β, Wnt1 and PRDX3 in Hirschsprung's disease
Authors: Gao Hong , Liu Xiaomei , Chen Dong , Lv Liangying , Wu Mei , Mi Jie , Wang Weilin
Published: April 2014

Hirschsprung's disease (HSCR) is a developmental disorder of the enteric nervous system characterized by aganglionosis in distal gut. In this study, we used two‐dimensional gel electrophoresis (2‐DE) technology coupled with matrix assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS) analysis to identify differentially expressed proteins in the aganglionic (stenotic) and ganglionic (normal) colon segment tissues from patients with HSCR. We identified 15 proteins with different expression levels between the stenotic and the normal colon segment tissues from patients with HSCR. Nine proteins were upregulated and six proteins downregulated in the stenotic colon segment tissues compared to the normal colon segment tissues. Based on the biological functions, we selected the Hsp27 upregulated proteins and the PRDX3 downregulated proteins to confirm their expression in 20 patients. The protein and mRNA expressions of Hsp27 were statistically higher in the stenotic colon segment tissues than in the normal colon segment tissues, whereas the protein and mRNA expressions of PRDX3 were statistically lower in the stenotic colon segment tissues than in the normal colon segment tissues. These findings of changes in mRNA and protein in tissues from patients with HSCR provide information which may be helpful in understanding the pathomechanism that is implicated in the disease.
A novel KIR3DS1*0130107 allele isolated by sequencing from an Asian donor
Authors: Yindom L.‐M. , Wang L. , Xu K. , Dong T. , Rowland‐Jones S. L.
Published: April 2014

This novel KIR3DS1 allele officially named as KIR3DS1*0130107 was isolated from DNA samples from Asia using high‐resolution sequenced‐based techniques. KIR3DS1*0130107 differs from the first member of the KIR3DS1*013 subgroup (KIR3DS1*0130101) by a single mutation at position 8922A>G (intron 5), just nine nucleotides away from the start of exon 6.
Clinical and Radiological Heterogeneity in Aneurysmal Sub-Arachnoid Haemorrhage According to Risk-Factor Profile
Authors: Nieuwkamp Dennis J. , Algra Ale , Velthuis Birgitta K. , Rinkel Gabriël J.E.
Published: April 2014

Background and Aim

Risk factors for aneurysmal sub-arachnoid haemorrhage can be divided into environmental and inherited factors; the latter being presumed more important in young patients. We explored in young sub-arachnoid haemorrhage patients whether risk-factor profiles influence clinical and radiological characteristics of aneurysms and sub-arachnoid haemorrhage.

Methods

From the 2139 aneurysmal sub-arachnoid haemorrhage patients who had been entered in our prospectively collected database between January 1997 and August 2012, we retrieved data on young (18–40 years) aneurysmal sub-arachnoid haemorrhage patients and compared those with smoking or hypertension (atherogenic risk factors) with those without. Clinical and radiological characteristics were compared with risk ratios and corresponding 95% confidence intervals. Possible confounding by age and gender was adjusted with multivariable Poisson regression analysis.

Results

Patients with atherogenic risk factors ( n = 113) were less often female (risk ratio: 0·7; 95% confidence interval: 0·6↔0·9), had less often a small aneurysm (risk ratio: 0·4; 95% confidence interval: 0·2↔0·7), and tended to have less often middle cerebral artery aneurysms (risk ratio: 0·5; 95% confidence interval: 0·3↔1·1) than the 29 patients without these risk factors. After adjustment for gender and age, patients with atherogenic risk factors had more often multiple aneurysms (risk ratio: 7·5; 95% confidence interval: 1·1↔52·9). There were no overt differences in the amount of cisternal and intraventricular blood, the shape of the aneurysm, and configuration of the circle of Willis between the patient groups. After adjustment for gender and age, patients with atherogenic risk factors had more often poor outcome (risk ratio: 3·8; 95% confidence interval: 1·0↔14·5).

Conclusions

Young sub-arachnoid haemorrhage patients without atherogenic risk factors are rare. Clinical and radiological characteristics vary between sub-arachnoid haemorrhage patients with different risk-factor profiles. This clinical heterogeneity should be taken into account in future genetic and other etiological studies.
Forecasting Immigration in Official Population Projections Using an Econometric Model
Authors: Cappelen Ådne , Skjerpen Terje , Tønnessen Marianne
Published: April 2014

Although substantial research has been conducted to quantify the determinants of international migration, most official population projections do not include such determinants in a formal migration model. Statistics Norway forecasts gross immigration to Norway using an econometric model based on standard migration theories. The main variables include income level, unemployment, and population size in Norway and the sending countries, and the number of immigrants already living in Norway. Projections of exogenous variables are drawn from international and Norwegian sources. Three different alternatives are specified for the income variables, leading to three different forecasts for gross immigration until 2100.
Effects of Mild and Severe Drought Stress on Photosynthetic Efficiency in Tolerant and Susceptible Barley (Hordeum vulgare L.) Genotypes
Authors: Ghotbi‐Ravandi A. A. , Shahbazi M. , Shariati M. , Mulo P.
Published: April 2014

Drought stress is one of the most important abiotic factors which adversely affect growth, metabolism and yield of crops worldwide. The objective of this study was to determine the effects of drought stress on photosynthesis in barley and examine the differential responses of photosynthetic apparatus in relatively tolerant (Yousof) and susceptible (Morocco) barley genotypes. Plants were subjected to different levels of soil water availability including control, mild and severe drought stress. In both genotypes, drought stress led to decrease in chlorophylls, β‐carotene and stomatal conductance accompanied by decrease in CO2 assimilation rate. Significant increase in α‐tochoperol content was only observed in Yousof cultivar under drought stress. Initial slope and plateau phase of CO2 response curve of drought‐stressed plants as well as polyphasic chlorophyll a fluorescence transient curve (OJIP test) and fast fluorescence induction kinetics were influenced by drought stress. These parameters were more affected in Morocco cultivar by drought stress compare with Yousof. Drought stress also resulted in reduction of D1 protein content in both genotypes and accelerated photoinhibition process. Based on our results, stomatal conductance is the main factor limiting photosynthesis in Yousof genotype under mild drought stress. However, in Morocco, in addition to stomatal limitation, damage to photosystem II (PSII), reduced electron transport and carboxylation efficiencies were important parts of limitation in photosynthesis. Severe drought stress resulted in structural and biochemical impairment of light‐dependent reactions as well as carboxylation process of photosynthesis in both genotypes. Alpha‐tocopherol showed an important protective role against drought stress in Yousof cultivar as a relatively drought‐tolerant cultivar.
Antioxidant Activity in Salt‐Stressed Barley Leaves: Evaluating Time‐ and Age‐Dependence and Suitability for the Use as a Biochemical Marker in Breeding Programs
Authors: Fan Y. , Zhu M. , Shabala S. , Li C. D. , Johnson P. , Zhou M. X.
Published: April 2014

Soil salinity disturbs the equilibrium between reactive oxygen species (ROS) production and removal, leading to a dramatic increase in ROS concentration and oxidative damage. Enzymatic scavenging is one of the two main mechanisms involved in ROS detoxification in plants. This study has investigated the role of major antioxidant (AO) enzymes in mitigating salinity‐induced oxidative stress in plant shoots. Firstly, two barley varieties were used to evaluate the activity of major AO enzymes in different leaves and at different times after salt treatment. Our results showed that AO enzyme activities had strong tissue and time specificity. A further study was conducted using six barley varieties contrasting in salinity tolerance. AO enzyme activities and proline contents were measured in the third leaves of seedlings after plants were treated with 240 mm NaCl for 10 days. No significant correlation was revealed between leaf AO activity and either plant grain yield or plant survival rate under salt stress. In contrast, a significant increase in leaf proline content under salt stress was found in all sensitive varieties, while in most tolerant varieties, salt stress did not change leaf proline level. It is concluded that although salinity induces changes in leaf AO enzyme activities, the changes cannot be used as biochemical indicators in breeding for salinity tolerance.
Quinoa's Potential in the Mediterranean Region
Authors: Lavini A. , Pulvento C. , d'Andria R. , Riccardi M. , Choukr‐Allah R. , Belhabib O. , Yazar A. , İncekaya Ç. , Metin Sezen S. , Qadir M. , Jacobsen S.‐E.
Published: April 2014

The climate of Mediterranean region will become drier and hotter, with increased problems of soil salinity. A possible alternative to minimize the effects of climate change is to introduce species with better tolerance to salt and drought stresses. One of the options is quinoa (Chenopodium quinoa Willd.), which was grown in field trials in several Mediterranean countries, to study the effects of drought and salinity on yield and other characters. Drought stress during the vegetative growth stage leads to deep root development, and without stress conditions for the rest of the growing season allowed the plant to be able to optimize its photosynthesis and carbon translocation. Stress during seed filling recorded the lowest yields. The influence of organic matter on yield was more important under deficit irrigation than under full irrigation. The interaction between relative water content and leaf water potential indicated that regulating cellular water deficit and volume is a powerful mechanism for conserving cellular hydration under drought. In all climatic conditions, drought and use of irrigation water with salinity up to 30 dS m−1 caused slightly reduced yield as compared to full irrigation with fresh water. Highest values of water conductivity resulted in higher seed weight, and as a consequence, an increase in fibre and total saponin content, and a small decrease in free phenolic compounds in quinoa seeds. The yield increase in quinoa accessions was less at the highest level of nitrogen application, that is, 200 mg kg−1 soil, compared with other levels of nitrogen application, that is, 50, 100 and 150 mg kg−1 soil.
Behavioural cancer risk factors in women diagnosed with primary breast cancer
Authors: Del Valle María Olivo , Martin‐Payo Rubén , Lana Alberto , Garcia Juan Bautista , Folgueras María Victoria , Lopez María Luisa
Published: April 2014

Aims

To investigate behavioural risk factors and self‐efficacy among women diagnosed with breast cancer.

Background

The appearance of new tumours in breast cancer survivors is influenced by risk behaviours. Knowing their prevalence and women's perceived ability to adopt a healthy lifestyle would allow designing educational interventions aimed at modifying these behaviours.

Design

An observational cross‐sectional study of women diagnosed with breast cancer.

Methods

The study was carried out in Asturias (Spain). A total of 2407 breast cancer patients diagnosed between 1998–2008 were selected and 492 women agreed to participate. Self‐reported data on risk factors self‐efficacy were gathered through a telephone interview based on the European Code against Cancer conducted between February–June 2010.

Results

A total of 16·1% of women in this study were regular smokers, 5% drank alcohol excessively, 49% were overweight, 54% reported a lower level of physical activity than recommended and 7·5% did not use sun protection. The Total Cancer Behavioural Risk indicator was calculated by adding up the results of all modifiable risks contained in the European Code against Cancer, with an average score of 21·6 in a scale from 0–78 points (0 = null cancer risk, 78 = maximum cancer risk). Self‐efficacy levels were very high among our participants.

Conclusion

The results suggest that there is a need to design programmes to promote a healthy lifestyle among women diagnosed with breast cancer. Nurses have an important role to play in planning and implementing these programmes, using the most efficient educational techniques.
Blood Pressure Variability and Morning Blood Pressure Surge in Elderly Chinese Hypertensive Patients
Authors: Qin Xiaobo , Zhang Qin , Yang Suping , Sun Zhongbo , Chen Xiaojie , Huang Huiling
Published: April 2014

This retrospective study aimed to investigate blood pressure variability (BPV), morning systolic blood pressure surge (MBPS), and the associated factors in 513 elderly (65 years and older) and 188 younger (younger than 65 years) hypertensive Chinese patients who had ambulatory blood pressure monitoring (ABPM) at our hospital from January 1, 2002, to December 31, 2010. The MBPS was lower in the younger patients compared with the elderly patients, and it was highest in the 75 years and older and younger than 80 group (29.0±13.4 mm Hg). Compared with other groups, the 80 years and older group had a significant increase in BPV (P<.05). Multiple linear regression analysis showed that body mass index (BMI; P<.01), up to 50 years of smoking (P≤.03), and circadian blood pressure variation (P<.01) were factors associated with MPBS. In summary, systolic BPV and MBPS were increased in elderly Chinese hypertensive patients, and the MBPS was associated with BMI, years of smoking, and circadian blood pressure variation.