bluuebunny/crossref_metadata_2025 huggingface dataset:
Parametric bootstrap methods for testing multiplicative terms in GGE and AMMI models
Authors: Forkman Johannes , Piepho Hans‐Peter
Published: March 2014

The genotype main effects and genotype‐by‐environment interaction effects (GGE) model and the additive main effects and multiplicative interaction (AMMI) model are two common models for analysis of genotype‐by‐environment data. These models are frequently used by agronomists, plant breeders, geneticists and statisticians for analysis of multi‐environment trials. In such trials, a set of genotypes, for example, crop cultivars, are compared across a range of environments, for example, locations. The GGE and AMMI models use singular value decomposition to partition genotype‐by‐environment interaction into an ordered sum of multiplicative terms. This article deals with the problem of testing the significance of these multiplicative terms in order to decide how many terms to retain in the final model. We propose parametric bootstrap methods for this problem. Models with fixed main effects, fixed multiplicative terms and random normally distributed errors are considered. Two methods are derived: a full and a simple parametric bootstrap method. These are compared with the alternatives of using approximate F‐tests and cross‐validation. In a simulation study based on four multi‐environment trials, both bootstrap methods performed well with regard to Type I error rate and power. The simple parametric bootstrap method is particularly easy to use, since it only involves repeated sampling of standard normally distributed values. This method is recommended for selecting the number of multiplicative terms in GGE and AMMI models. The proposed methods can also be used for testing components in principal component analysis.
Accelerated intensity frailty model for recurrent events data
Authors: Liu Bo , Lu Wenbin , Zhang Jiajia
Published: March 2014

In this article we propose an accelerated intensity frailty (AIF) model for recurrent events data and derive a test for the variance of frailty. In addition, we develop a kernel‐smoothing‐based EM algorithm for estimating regression coefficients and the baseline intensity function. The variance of the resulting estimator for regression parameters is obtained by a numerical differentiation method. Simulation studies are conducted to evaluate the finite sample performance of the proposed estimator under practical settings and demonstrate the efficiency gain over the Gehan rank estimator based on the AFT model for counting process (Lin et al., 1998). Our method is further illustrated with an application to a bladder tumor recurrence data.
A statistical approach to set classification by feature selection with applications to classification of histopathology images
Authors: Jung Sungkyu , Qiao Xingye
Published: March 2014

Set classification problems arise when classification tasks are based on sets of observations as opposed to individual observations. In set classification, a classification rule is trained with N sets of observations, where each set is labeled with class information, and the prediction of a class label is performed also with a set of observations. Data sets for set classification appear, for example, in diagnostics of disease based on multiple cell nucleus images from a single tissue. Relevant statistical models for set classification are introduced, which motivate a set classification framework based on context‐free feature extraction. By understanding a set of observations as an empirical distribution, we employ a data‐driven method to choose those features which contain information on location and major variation. In particular, the method of principal component analysis is used to extract the features of major variation. Multidimensional scaling is used to represent features as vector‐valued points on which conventional classifiers can be applied. The proposed set classification approaches achieve better classification results than competing methods in a number of simulated data examples. The benefits of our method are demonstrated in an analysis of histopathology images of cell nuclei related to liver cancer.
Impact of comorbidity on health‐related quality of life after prostate cancer treatment: combined analysis of two prospective cohort studies
Authors: Reeve Bryce B. , Chen Ronald C. , Moore Dominic T. , Deal Allison M. , Usinger Deborah S. , Lyons Jessica C. , Talcott James A.
Published: March 2014

Objective

To improve and individualise estimates of treatment outcomes for men diagnosed with prostate cancer, we examined the impact of baseline comorbidity on health‐related quality of life (HRQL) outcomes in an analysis of two pooled, prospective cohort studies.

Patients and Methods

We studied 697 patients from three academic hospitals who received radical prostatectomy (RP), external beam radiation therapy (EBRT), or brachytherapy (BT). Measures of patient‐reported bowel, urinary, and sexual symptoms along with physical and mental health were prospectively collected before treatment and 3, 12, 24, and 36 months after treatment. We assessed baseline comorbidity by the validated Index of Co‐Existent Disease (ICED), abstracted from medical records. Regression mixed‐models were built for each treatment group and HRQL outcome controlling for baseline age, education, marital status, risk group and patient‐reported general health.

Results

About 71% of patients had one or more comorbid conditions at baseline. After adjusting for covariates, we found baseline comorbidity was independently associated with poorer sexual function after BT (P = 0.04) and RP (P = 0.03) but not EBRT (P = 0.35). Physical health was significantly worse for men receiving BT with more comorbidities (P = 0.02). Baseline comorbid conditions were not associated with urinary incontinence or bowel functioning.

Conclusions

Comorbidity at baseline is significantly associated with poorer sexual function after prostate BT or RP. This information may help patients and their physicians anticipate outcomes after surgical and radiation treatments.
Disturbance Level Determines the Regeneration of Commercial Tree Species in the Eastern Amazon
Authors: Schwartz Gustavo , Lopes José C. , Kanashiro Milton , Mohren Godefridus M. , Peña‐Claros Marielos
Published: March 2014

The effects of reduced‐impact logging (RIL) on the regeneration of commercial tree species were investigated, as long‐term timber yields depend partly on the availability of seedlings in a managed forest. On four occasions during a 20‐month period in the Tapajós National Forest (Eastern Amazon, Brazil), seven commercial tree species were assessed as follows: the long‐lived pioneers Bagassa guianensis and Jacaranda copaia; the partially shade‐tolerant Hymenaea courbaril, Dipteryx odorata, and Carapa guianensis; and the totally shade‐tolerant Symphonia globulifera and Manilkara huberi. In 2439 10 × 10 m plots, all individuals < 20 cm diameter at breast height (dbh) were assessed over three intervals, before, during, and after the forest being logged. Before logging, the density of seedlings and saplings of the seven species did not change. Logged trees were spatially aggregated, with 9.2 percent of the plots being heavily impacted by logging. After logging, the recruitment rate increased more than the mortality rate, so that post‐harvesting densities of seedlings and saplings increased. The increase in density was concentrated in logged plots with more disturbances. It is concluded that post‐harvesting heterogeneity of micro‐environments created by RIL may be an important component to be taken into account for sustainable forest management and conservation of commercial species.
Mixed‐species Groups of Marmosets and Tamarins Across a Gradient of Agroforestry Intensification
Authors: Tisovec Karina C. , Cassano Camila R. , Boubli Jean P. , Pardini Renata
Published: March 2014

Polyspecific associations are commonly observed in social animals, including primates, and have been interpreted as adaptations either to improve access to resources or to provide protection against predators. Mixed‐species associations between Wied's marmosets (Callithrix kuhlii) and golden‐headed lion tamarins (Leontopithecus chrysomelas) have been documented, and are unique among Atlantic forest primates. Both species are endemic to southern Bahia where part of the forest has been converted into cacao agroforests, which have been subjected to management intensification. Tree density and canopy connectivity decrease in more intensively managed agroforests, potentially increasing predation risk and the frequency of mixed‐species groups between these primates. Here, we test this hypothesis using a standardized, large spatial‐scale data set obtained from camera‐trapping in 30 sites across an agroforestry landscape mosaic. As expected, the frequency of mixed‐species groups increased in more intensively managed agroforests, but only relative to the total number of records of tamarins. Our results highlight that the benefits of mixed‐species groups can be asymmetrical among species and variable across the landscape. They corroborate that predation avoidance is an important advantage of mixed‐species groups in callitrichids, especially for conspicuous species living in smaller groups, such as the tamarin. Despite the importance of agroforests to conservation, our results indicate that management intensification can increase predation risk for species of conservation concern. To maintain the conservation value of agroforests, management practices should be planned to avoid any loss of canopy connectivity, taking into account the biodiversity vs. productivity trade‐off associated with shade management.
Immunocompatibility and Toxicity Studies of Poly‐L‐Lysine Nanocapsules in Sprague–Dawley Rats for Drug‐Delivery Applications
Authors: Ayyappan Janeesh Plakkal , Sami Haider , Rajalekshmi Dhanya Chandrasekharan , Sivakumar Sri , Abraham Annie
Published: March 2014

Poly‐L‐Lysine (PLL) nanocapsules are the emerging drug‐delivery vehicle for the therapeutics of targeted diseases. The study was designed for the synthesis and characterization of PLL nanocapsules and to know its immunocompatibility and toxicity behavior for in vivo drug‐delivery applications. Alteration in hematologic parameters, immunomodulatory gene expression by RT‐PCR studies, toxicity markers status, immunoblotting of major inflammatory marker proteins, and histopathologic studies from major tissues of rat after intravenous administration of PLL nanocapsules after 30 days were assessed. In vivo toxicity markers activity, hematologic parameters alteration, and RT‐PCR analysis of important immunomodulatory genes such as monocyte chemotactic protein‐1(MCP 1), tumor necrosis factor‐alpha (TNF‐α), Intercellular adhesion molecule‐1 (ICAM‐1), and interleukin‐6 (IL‐6) showed least changes when compared with control. The immunoblotting of major inflammatory markers such as cyclooxygenase‐2 (COX‐2), lipo‐oxygenase‐15 (LOX‐15), and nitric oxide synthase (NOS) found have least expression showing the immunocompatibility of PLL nanocapsules. Histopathologic studies of important tissues showed almost normal architecture after treatment using different concentration of PLL nanocapsules after the experimental period. The results showed a promising outcome and further confirmed the immunocompatibility and non‐toxicity of PLL nanocapsules in vivo for drug‐delivery applications.
BSACI guideline for the diagnosis and management of cow's milk allergy
Authors: Luyt D. , Ball H. , Makwana N. , Green M. R. , Bravin K. , Nasser S. M. , Clark A. T.
Published: March 2014

This guideline advises on the management of patients with cow's milk allergy. Cow's milk allergy presents in the first year of life with estimated population prevalence between 2% and 3%. The clinical manifestations of cow's milk allergy are very variable in type and severity making it the most difficult food allergy to diagnose. A careful age‐ and disease‐specific history with relevant allergy tests including detection of milk‐specific IgE (by skin prick test or serum assay), diagnostic elimination diet, and oral challenge will aid in diagnosis in most cases. Treatment is advice on cow's milk avoidance and suitable substitute milks. Cow's milk allergy often resolves. Reintroduction can be achieved by the graded exposure, either at home or supervised in hospital depending on severity, using a milk ladder. Where cow's milk allergy persists, novel treatment options may include oral tolerance induction, although most authors do not currently recommend it for routine clinical practice. Cow's milk allergy must be distinguished from primary lactose intolerance. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for clinicians in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking the panel of experts in the committee reached consensus. Grades of recommendation are shown throughout. The document encompasses epidemiology, natural history, clinical presentations, diagnosis, and treatment.
Evaluation of adrenal function in critically ill children
Authors: Balbão Viviane M. P. , Costa Marcela M. A. , Castro Margaret , Carlotti Ana P. C. P.
Published: March 2014

Objective

There is no consensus on adequate adrenal response to critical illness. We aimed to evaluate adrenal function in critically ill children and its association with clinical outcome. We hypothesized that salivary cortisol would be a more appropriate tool to evaluate adrenal function in critically ill children.

Methods

This was a prospective cohort study. The concentrations of serum total and salivary cortisol were measured in 34 critically ill children before and after stimulation with 250 μg adrenocorticotropic hormone (ACTH), and values were compared to a control group of healthy children (n = 15). Association between outcome and adrenal insufficiency defined by an increment in serum cortisol ≤250 nm (9 μg/dl) post‐ACTH was assessed.

Results

Serum total and salivary cortisol concentrations pre‐ and post‐ACTH were significantly higher in patients, and they were correlated at baseline (r = 0·67; P < 0·0001) and after ACTH (r = 0·41; P = 0·02). The incidence of adrenal insufficiency was 32·3%. This group had higher Paediatric Risk of Mortality III score (P = 0·04) but Paediatric Logistic Organ Dysfunction and vasoactive inotropic scores, duration of mechanical ventilation and length of paediatric intensive care unit and hospital stay were not significantly different compared with those with an increment >250 nm (9 μg/dl) post‐ACTH. An inverse correlation between salivary cortisol post‐ACTH and vasoactive inotropic score (r = −0·56; P = 0·0008) was observed. A salivary cortisol concentration post‐ACTH of ≤226 nm (8·2 μg/dl) had a sensitivity of 79% and a specificity of 62% to discriminate need for vasoactive or inotropic support (area under receiver operating characteristic (ROC) curve 0·74).

Conclusion

Adrenal insufficiency defined by the ‘delta criterion’ was not associated with outcome. A post‐ACTH salivary cortisol of ≤226 nm (8·2 μg/dl) may be suggestive of an insufficient adrenal response to critical illness.
Continuous Self‐Collision Detection for Deformable Surfaces Interacting with Solid Models
Authors: Wong Sai‐Keung , Cheng Yu‐Chun
Published: March 2014

In this paper, we propose a new continuous self‐collision detection (CSCD) method for a deformable surface that interacts with a simple solid model. The method is developed based on the radial‐view‐based culling method. Our method is suitable for the deformable surface that has large contact region with the solid model. The deformable surface may consist of small round‐shaped holes. At the pre‐processing stage, the holes of the deformable surface are filled with ghost triangles so as to make the mesh of the deformable surface watertight. An observer primitive (i.e. a point or a line segment) is computed so that it lies inside the solid model. At the runtime stage, the orientations of triangles with respect to the observer primitive are evaluated. The collision status of the deformable surface is then determined. We evaluated our method for several animations including virtual garments. Experimental results show that our method improves the process of CSCD.
On the relationship between gingival biotypes and gingival thickness in young Caucasians
Authors: Fischer Kai R. , Richter Timo , Kebschull Moritz , Petersen Nicole , Fickl Stefan
Published: March 2014

Objectives

To evaluate a possible relationship between gingival biotypes and gingival thickness, papilla height and gingival width.

Material and methods

Thirty‐six adult subjects were stratified by their gingival biotype (GB), as defined by transparency of a periodontal probe through the buccal gingival margin, into “thin” (18 subjects) and “thick” (18 subjects) GB. Out of these, extreme cases (6 “very thin”, 6 “very thick”) were identified. Four different parameters were assessed: gingival thickness (GT), papilla height (PH), probing depth (PD) and gingival width (GW).

Results

When comparing “thin” and “thick” GB, midfacial GT (0.40 ± 0.07 vs. 0.72 ± 0.11 mm; P < 0.0001), PH (3.76 ± 0.50 vs. 3.95 ± 0.41 mm, P = 0.02) and GW (3.01 ± 1.26 vs. 4.63 ± 0.86 mm, P = 0.04) were lower in the “thin” GB group. Further stratification into moderately and extremely “thin”/“thick” GB eliminated the differences between the moderate groups.

Conclusion

Our data support the traditional hypothesis that two different gingival biotypes with concomitant properties distinguishable by gingival transparency exist. In addition, we provide evidence that an alternative classification into “very thick”, “moderate” and “very thin” biotypes might be advantageous, because the unique properties were seemingly primarily driven by subjects with extreme values.
Flap versus flapless procedure for ridge preservation in alveolar extraction sockets: a histological evaluation in a randomized clinical trial
Authors: Barone Antonio , Borgia Valentina , Covani Ugo , Ricci Massimiliano , Piattelli Adriano , Iezzi Giovanna
Published: March 2014

Objective

The aim of this study was to evaluate and compare the histological and histomorphometric features of two different procedures carried out in extraction socket grafting; namely, the flapped and flapless technique.

Materials and methods

Patients considered eligible for the study were randomized to receive tooth extraction and ridge preservation with the porcine bone and collagen membrane, with a full thickness mucoperiosteal flap and primary soft tissue closure (control group), or, with a flapless procedure and a secondary soft tissue closure (test group). After 3 months of healing, the surgical re‐entry procedure was performed and implants were inserted in the test as well as in the control sites. Bone core samples were harvested from both groups and processed to be observed under light microscopy. Outcome variables were percentages of newly formed bone, residual graft particles and marrow spaces.

Results

Thirty‐four patients were enrolled in the study. All of the scheduled implants were placed. Histological and histomorphometrical analyses did not report significant differences between the two groups (with P‐values ranging from 0.690 to 0.917). The mean percentages of newly formed bone, soft tissues and residual grafted particles were 22.5 and 22.5%, 59.3 and 59.4%, and 18.6 and 18.2% respectively for flap and flapless approach.

Conclusion

No histological and histomorphometrical differences were observed when comparing the flap and the flapless technique for tooth extraction and socket grafting procedures.
Tenting effect of the elevated sinus membrane over an implant with adjunctive use of a hydroxyapatite‐powdered collagen membrane in rabbits
Authors: Jung Ui‐Won , Unursaikhan Otgonbayar , Park Jin‐Young , Lee Jung‐Seok , Otgonbold Jamiyandorj , Choi Seong‐Ho
Published: March 2014

Purpose

The aim of this study was to determine the de novo bone formation beneath the Schneiderian membrane supported by an implant and with the adjunctive use of a hydroxyapatite‐powdered collagen (HAC) membrane without bone grafting in rabbit sinuses.

Material and methods

After sinus‐floor elevation procedure, an experimentally devised mini‐implant (4 mm in length and 3 mm in diameter) was placed in eight rabbits. For the experimental group, an HAC membrane was placed onto the elevated sinus mucosa prior to implant placement. The animals were allowed a healing period of either 4 or 8 weeks. Microcomputed tomography and histologic analyses were performed.

Results

All implants placed at the thin lateral bony wall were histologically osseointegrated. The topography of the newly formed bone appeared to slope gently from the medial side down to the lateral side. The volume of new bone was significantly greater in the experimental group than in the control group at 4 weeks (P < 0.05), but not at 8 weeks. However, none of the samples in the two groups was entirely covered to the apex by bone tissue.

Conclusions

It can be concluded that using the HAC membrane in combination with placement of an implant resulted in substantial bone formation around the implant, which might have been influenced by the proximity of the axial bony wall.
Long‐Acting Versus Standard Non‐Ergot Dopamine Agonists in Parkinson's Disease: A Meta‐Analysis of Randomized Controlled Trials
Authors: Zhou Chang‐Qing , Lou Jing‐He , Zhang Yu‐Ping , Zhong Ling , Chen Ya‐Lan , Lu Feng‐Jiao , Peng Guo‐Guang
Published: March 2014

Aims

To evaluate the efficacy, tolerability, and safety of long‐acting versus standard non‐ergot dopamine agonists (NEDAs) in Parkinson's disease (PD), we performed a meta‐analysis of randomized controlled trials (RCTs).

Materials and methods

The PubMed, EMBASE, Cochrane Library databases, and Web of Knowledge were searched up to November 20th 2013. The pooled weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated.

Results

Eight large‐scale RCTs, involving 2402 patients, were included in this meta‐analysis. Compared with the standard NEDAs, long‐acting NEDAs exhibited similar improvements in Unified Parkinson's Disease Rating Scale activities of daily living (ADL) score (WMD 0.09, 95% CI −0.33 to 0.50), motor score (WMD −0.35, 95% CI –1.60 to 0.90), and “off” time (WMD 0.18, 95% CI −0.14 to 0.50). No differences were found in overall withdrawals (RR 1.11, 95% CI 0.94 to 1.32), withdrawals due to adverse events (RR 1.19, 95% CI 0.91 to 1.56), or the ten commonly reported adverse events between the two formulations.

Conclusions

Our meta‐analysis showed long‐acting NEDAs were noninferior to standard NEDAs in efficacy, tolerability, and safety in the treatment of PD.
Shuttle walking test in obese women: test‐retest reliability and concurrent validity with peak oxygen uptake
Authors: Jürgensen Soraia P. , Trimer Renata , Dourado Victor Z. , Di Thommazo‐Luporini Luciana , Bonjorno‐Junior José C. , Oliveira Cláudio R. , Arena Ross , Mendes Renata G. , Borghi‐Silva Audrey
Published: March 2014

Objective

The aim of this study was to evaluate the test–retest reliability, concurrent validity and agreement with peak oxygen uptake (VO2) obtained during cardiopulmonary exercise testing (CPX) on a treadmill for the incremental shuttle walking test (ISWT) in obese women.

Methods

Prospective study with a convenient sample of 46 community‐dwelling obese women (BMI > 30 kg m−2). The main outcome measures were walking distance on theISWTand peakVO2.

Results

Test–retest reliability was good to excellent for the exercise tests (ISWTdistanceICC: 0·90; andCPXpeakVO2ICC: 0·90). PeakVO2obtained duringCPXcorrelated significantly withISWTdistance (r = 0·54,P<0·05) and peakVO2obtained during theISWT(r = 0·64,P<0·05). Bland and Altman plots demonstrated a high degree of repeatability.

Conclusion

TheISWThad excellent reliability as well as good concurrent validity and agreement. TheISWTmay be a potential tool for monitoring clinical status and intervention efficacy (e.g. programmes for weight loss and rehabilitative strategies) in this population.
Macrophages – sensors and effectors coordinating skin damage and repair
Authors: Willenborg Sebastian , Eming Sabine A.
Published: March 2014

Restoration of skin integrity and homeostasis following injury is a vital process. Wound healing disorders, including chronic skin ulcers and pathological scarring, are of major clinical impact. The current therapeutic approaches are often not sufficient. The development of novel efficient therapies requires a thorough understanding of the underlying molecular mechanisms. A cardinal feature of non‐healing skin ulcers and excessive scarring is a prolonged inflammatory response at the wound site, which aborts the healing response. Modulation of the local immune response may be an effective therapeutic strategy to correct impaired healing conditions. Yet, the specific mechanisms of inflammation, particularly the role of the diverse leukocyte lineages attracted to the site of tissue damage, have not been resolved. Recent findings in diverse experimental model systems and clinical studies have refined the understanding of monocyte/macrophage biology and the role of cells of the monocytic lineage in tissue regeneration. Thus, monocytes/macrophages are emerging as novel and interesting therapeutic targets to interfere in wound healing pathologies. In this article we will review the role of monocytes/macrophages in skin repair in the light of the recent literature and findings from our own group. This article will provide a rationale for monocyte/macrophage‐based therapies to facilitate the healing response.
Numerical predictors of arithmetic success in grades 1–6
Authors: Lyons Ian M. , Price Gavin R. , Vaessen Anniek , Blomert Leo , Ansari Daniel
Published: March 2014

Math relies on mastery and integration of a wide range of simpler numerical processes and concepts. Recent work has identified several numerical competencies that predict variation in math ability. We examined the unique relations between eight basic numerical skills and early arithmetic ability in a large sample (N = 1391) of children across grades 1–6. In grades 1–2, children's ability to judge the relative magnitude of numerical symbols was most predictive of early arithmetic skills. The unique contribution of children's ability to assess ordinality in numerical symbols steadily increased across grades, overtaking all other predictors by grade 6. We found no evidence that children's ability to judge the relative magnitude of approximate, nonsymbolic numbers was uniquely predictive of arithmetic ability at any grade. Overall, symbolic number processing was more predictive of arithmetic ability than nonsymbolic number processing, though the relative importance of symbolic number ability appears to shift from cardinal to ordinal processing.
The roles of family history of dyslexia, language, speech production and phonological processing in predicting literacy progress
Authors: Carroll Julia M. , Mundy Ian R. , Cunningham Anna J.
Published: March 2014

It is well established that speech, language and phonological skills are closely associated with literacy, and that children with a family risk of dyslexia (FRD) tend to show deficits in each of these areas in the preschool years. This paper examines what the relationships are between FRD and these skills, and whether deficits in speech, language and phonological processing fully account for the increased risk of dyslexia in children with FRD. One hundred and fifty‐three 4–6‐year‐old children, 44 of whom had FRD, completed a battery of speech, language, phonology and literacy tasks. Word reading and spelling were retested 6 months later, and text reading accuracy and reading comprehension were tested 3 years later. The children with FRD were at increased risk of developing difficulties in reading accuracy, but not reading comprehension. Four groups were compared: good and poor readers with and without FRD. In most cases good readers outperformed poor readers regardless of family history, but there was an effect of family history on naming and nonword repetition regardless of literacy outcome, suggesting a role for speech production skills as an endophenotype of dyslexia. Phonological processing predicted spelling, while language predicted text reading accuracy and comprehension. FRD was a significant additional predictor of reading and spelling after controlling for speech production, language and phonological processing, suggesting that children with FRD show additional difficulties in literacy that cannot be fully explained in terms of their language and phonological skills.
Understanding the mapping between numerical approximation and number words: evidence from Williams syndrome and typical development
Authors: Libertus Melissa E. , Feigenson Lisa , Halberda Justin , Landau Barbara
Published: March 2014

All numerate humans have access to two systems of number representation: an exact system that is argued to be based on language and that supports formal mathematics, and an Approximate Number System (ANS) that is present at birth and appears independent of language. Here we examine the interaction between these two systems by comparing the profiles of people with Williams syndrome (WS) with those of typically developing children between ages 4 and 9 years. WS is a rare genetic deficit marked by fluent and well‐structured language together with severe spatial deficits, deficits in formal math, and abnormalities of the parietal cortex, which is thought to subserve the ANS. One of our tasks, requiring approximate number comparison but no number words, revealed that the ANS precision of adolescents with WS was in the range of typically developing 2‐ to 4‐year‐olds. Their precision improved with age but never reached the level of typically developing 6‐ or 9‐year‐olds. The second task, requiring verbal number estimation using number words, revealed that the estimates produced by adolescents with WS were comparable to those of typically developing 6‐ and 9‐year‐olds, i.e. were more advanced than their ANS precision. These results suggest that ANS precision is somewhat separable from the mapping between approximate numerosities and number words, as the former can be severely damaged in a genetic disorder without commensurate impairment in the latter.
Young children ‘solve for x’ using the Approximate Number System
Authors: Kibbe Melissa M. , Feigenson Lisa
Published: March 2014

The Approximate Number System (ANS) supports basic arithmetic computation in early childhood, but it is unclear whether the ANS also supports the more complex computations introduced later in formal education. ‘Solving for x’ in addend‐unknown problems is notoriously difficult for children, who often struggle with these types of problems well into high school. Here we asked whether 4–6‐year‐old children could solve for an unknown addend using the ANS. We presented problems either symbolically, using Arabic numerals or verbal number words, or non‐symbolically, using collections of objects while preventing verbal counting. Across five experiments, children failed to identify the value of the unknown addend when problems were presented symbolically, but succeeded when problems were presented non‐symbolically. Our results suggest that, well before formal exposure to unknown‐addend problems, children appear to ‘solve for x’ in an intuitive way, using the ANS.
Visual sensory and perceptive functioning in 5‐year‐old very preterm/very‐low‐birthweight children
Authors: Geldof Christiaan JA , Oosterlaan Jaap , Vuijk Pieter Jelle , de Vries Meindert J , Kok Joke H , van Wassenaer‐Leemhuis Aleid G
Published: March 2014

Aim

To examine visual sensory and perceptive functions, study their interrelations, and explore associations between visual dysfunctions and intelligence in very preterm/very‐low‐birthweight (VP/VLBW) children.

Method

One‐hundred and sixteen VP/VLBW children (57 males, 59 females; mean gestational age 30.1wks, SD 2.3; mean corrected age 5y 6mo, SD 1mo) and 73 term‐born children (40 males, 33 females; mean gestational age 39.9wks, SD 1.3; mean age 5y 6mo, SD 3mo) completed visual sensory (acuity, visual field, contrast‐, color‐, and stereovision), perceptive (visual coherence, and Developmental Test of Visual Perception non‐motor scale), and intelligence assessments.

Results

Compared with term‐born children, VP/VLBW children had reduced acuity (d=0.70, p<0.001), inferior visual field (d=0.67, p<0.001), and stereovision (v=0.19, p=0.008). VP/VBLW children showed weaker static coherence (d=0.49, p=0.001) and Position in Space (d=0.41, p=0.006) performance, independent of visual sensory deficits, and showed lower Verbal IQ (VIQ) and Performance IQ (PIQ; p<0.001). Visual perceptive functioning accounted for 13% of variance in VIQ, and for 35% of variance in PIQ.

Interpretation

Visual sensory and perceptive dysfunctions are present in VP/VLBW children and occur largely independently of each other. Visual perceptive dysfunctions are moderately associated with PIQ, and weakly with VIQ.
The contribution of platelet studies to the understanding of disease mechanisms in complex and monogenetic neurological disorders
Authors: Goubau Christophe , Buyse Gunnar M , Van Geet Chris , Freson Kathleen
Published: March 2014

Platelets, known for their role in primary haemostasis, prevent excessive bleeding after injury. The study of platelets has, therefore, traditionally focused on bleeding disorders. It has recently become evident, however, that platelet research can contribute to unravelling the disease mechanisms that underlie neuropathological disorders that have a subtle subclinical platelet phenotype. Platelets and neurosecretory cells have common gene expression profiles and share several biological features. This review provides a literature update on the use of platelets as easily accessible cells to study neurological disorders. We provide examples of the use of different platelet‐based tests to understand the underlying pathophysiological mechanisms for both complex and monogenetic neuropathological disorders. In addition to the well‐studied regulated granule secretion and serotonin metabolism, more recent studies have shown that defects in transcription factors, membrane transporters, G‐protein signal transduction, and cytoskeletal proteins can be investigated using platelets to gain information on their role in neuropathology.
Improved real‐world glycaemic outcomes with liraglutide versus other incretin‐based therapies in type 2 diabetes
Authors: Lee W. C. , Dekoven M. , Bouchard J. , Massoudi M. , Langer J.
Published: March 2014

Aim

Liraglutide (LIRA) once‐daily has provided greater A1C reductions than either exenatide (EXEN) twice‐daily or sitagliptin (SITA) once‐daily in head‐to‐head trials. The objective of this analysis is to compare the real‐world clinical effectiveness of these agents in the USA.

Methods

Using the IMS Health (Alexandria, VA, USA) integrated claims database, A1C outcomes in patients aged ≥18 years with type 2 diabetes (T2D) who initiated either LIRA, EXEN or SITA (including SITA/metformin) were retrospectively compared. Patients included in the analysis had ≥1 prescription for LIRA, EXEN or SITA between January and December 2010 (index period) and persisted with their index treatment regimens for 6 months post‐index. Outcomes included changes in A1C from baseline (45 days pre‐index through 7 days post‐index) to follow‐up [6 months post‐index (±45)] and the proportion of patients reaching A1C<7%. Multivariable regression models adjusted for confounding factors (e.g. age, comorbidities, baseline A1C and background antidiabetic therapy).

Results

The predicted change in A1C from baseline was greater for LIRA patients compared with both SITA (−1.08 vs. −0.68%; treatment difference 0.40%, p < 0.0001) and EXEN (−1.08 vs. −0.75%; treatment difference 0.32%, p < 0.001). Predicted A1C goal achievement, derived from the multivariate logistic regression model, was higher with LIRA compared with both SITA [64.4% (95% confidence interval, CI: 63.5–65.3) vs. 49.4% (95% CI: 48.5–50.4); p < 0.0001] and EXEN [64.4% (95% CI: 63.5–65.3) vs. 53.6% (95% CI: 52.6–54.6); p < 0.0001].

Conclusions

In clinical practice, LIRA was associated with significantly greater reductions in A1C and improved glycaemic goal attainment compared with either EXEN or SITA among adult patients with T2D.
Specific activation of the paralemniscal pathway during nociception
Authors: Frangeul Laura , Porrero Cesar , Garcia‐Amado Maria , Maimone Benedetta , Maniglier Madlyne , Clascá Francisco , Jabaudon Denis
Published: March 2014

Two main neuronal pathways connect facial whiskers to the somatosensory cortex in rodents: (i) the lemniscal pathway, which originates in the brainstem principal trigeminal nucleus and is relayed in the ventroposterior thalamic nucleus and (ii) the paralemniscal pathway, originating in the spinal trigeminal nucleus and relayed in the posterior thalamic nucleus. While lemniscal neurons are readily activated by whisker contacts, the contribution of paralemniscal neurons to perception is less clear. Here, we functionally investigated these pathways by manipulating input from the whisker pad in freely moving mice. We report that while lemniscal neurons readily respond to neonatal infraorbital nerve sectioning or whisker contacts in vivo, paralemniscal neurons do not detectably respond to these environmental changes. However, the paralemniscal pathway is specifically activated upon noxious stimulation of the whisker pad. These findings reveal a nociceptive function for paralemniscal neurons in vivo that may critically inform context‐specific behaviour during environmental exploration.
Conceptual Revision and Synthesis of Proximate Factors Associated with Age‐Related Improvement in Reproduction
Authors: Bradley Rachel J. , Safran Rebecca J.
Published: March 2014

Improvement in reproductive performance with age, up to the point of senescence, is a predominant pattern among vertebrates. Predictions from life‐history theory provide a powerful framework for understanding the evolutionary basis of these patterns. However, based on the growing number of publications on this topic, there is increased interest in understanding the proximate causes of age‐related improvements in reproductive performance (ARIRP). A formal conceptual framework through which factors related toARIRPcan be examined is lacking. Here, we establish hypotheses with testable predictions for social and ecological factors, including resource quality, mate fidelity, site fidelity, prior breeding experience, and changes in ability to attract mates. We use this conceptual framework to review 55 empirical studies published (between 1900 through 2013) on avian species as birds have the greatest representation in empirical studies ofARIRP. Our synthesis revealed that tests of the breeding experience hypothesis are most prevalent in the literature, whereas tests of the site fidelity hypothesis are least prevalent. Overall, the role of increased mate attraction with age seems to be an important predictor ofARIRP, whereas changes in resource quality with age show the least support among published studies. Because many studies suffered from small sample sizes and did not control for confounding variables, we suggest experimental methodologies for teasing apart hypotheses in empirical investigations and offer statistical approaches for longitudinal datasets. From an ultimate perspective, we also highlight the role of life‐history variation, in shaping within‐individual improvements. Future work should employ a standardized framework to study patterns ofARIRP, as set forward here, to allow for more quantitative comparison of results across studies.
Z‐Ligustilide inhibits benzo(a)pyrene‐induced CYP1A1 upregulation in cultured human keratinocytes via ROS‐dependent Nrf2 activation
Authors: Wu Zhouwei , Uchi Hiroshi , Morino‐Koga Saori , Nakamura‐Satomura Akiko , Kita Kazuyo , Shi Weimin , Furue Masutaka
Published: March 2014

Benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), is an environmental contaminant that can induce cytochrome P4501A1 (CYP1A1) upregulation via aryl hydrocarbon receptor (AhR) activation and provoke inflammation. Here, we investigated the effect of Z‐Ligustilide, an active ingredient isolated from the medicinal plants Cnidium officinale and Angelica acutiloba, on BaP‐induced CYP1A1 upregulation in normal human epidermal keratinocytes (NHEKs) as well as its underlying mechanisms. Z‐Ligustilide significantly inhibited BaP‐induced CYP1A1 upregulation in NHEKs. Treatment of NHEKs with Z‐Ligustilide induced Nuclear factor‐E2‐related factor 2 (Nrf2) nuclear translocation and expression of the Nrf2‐regulated genes for haeme oxygenase‐1 (HO‐1) and NAD(P)H:quinine oxidoreductase‐1 (NQO1). AhR silencing, SB203580 (a p38 inhibitor), SP600125 (a JNK inhibitor), U0126 (a MEK inhibitor) and LY294002 (a PI3K inhibitor) did not suppress Z‐Ligustilide‐induced Nrf2 activation. Moreover, treatment of NHEKs with Z‐Ligustilide increased reactive oxygen species (ROS) and L‐N‐acetylcysteine (L‐NAC, an antioxidant) attenuated Z‐ligustilide‐induced Nrf2 nuclear translocation and HO‐1 expression. L‐NAC or knock‐down of Nrf2 significantly attenuated the inhibitory effects of Z‐Ligustilide on BaP‐induced CYP1A1 upregulation in NHEKs. Taken together, these findings suggest that Z‐Ligustilide can suppress BaP‐induced CYP1A1 upregulation through ROS‐dependent Nrf2 pathway activation and may be beneficial in preventing or treating BaP‐induced skin damage.
Activation of Toll‐like receptors alters the microRNA expression profile of keratinocytes
Authors: Meisgen Florian , Xu Landén Ning , Bouez Charbel , Zuccolo Michela , Gueniche Audrey , Ståhle Mona , Sonkoly Enikö , Breton Lionel , Pivarcsi Andor
Published: March 2014

Keratinocytes recognize invading pathogens by various receptors, among them Toll‐like receptors (TLRs), and provide the first line of defense in skin immunity. The role of microRNAs in this important defense mechanism has not been explored yet. Our aim was to identify microRNAs involved in the innate immune response of keratinocytes. MicroRNA expression profiling revealed that the TLR2 ligand zymosan, the TLR3 ligand poly(I:C) or the TLR5 ligand flagellin significantly altered the microRNA expression in keratinocytes. The regulation of microRNAs was concentration‐dependent and it could be neutralized by siRNAs specific for TLR2, TLR3 and TLR5, respectively, confirming the specificity of the TLR response. Interestingly, one microRNA, miR‐146a, was strongly induced by all studied TLR ligands, while other microRNAs were regulated in a TLR‐ or time point‐specific manner. These findings suggest an important role for microRNAs in the innate immune response of keratinocytes and provide a basis for further investigations.
Signalling protein complexes isolated from primary human skin‐resident T cells can be analysed by Multiplex IP‐FCM
Authors: Smith Stephen E. P. , Neier Steven C. , Davis Tessa R. , Pittelkow Mark R. , Gil Diana , Schrum Adam G.
Published: March 2014

Studying signal transduction in skin‐resident T cells (sr‐T cells) can be limited by the small size of clinical biopsies. Here, we isolated sr‐T cells from clinical samples and analysed signalling protein complexes by multiplex immunoprecipitation detected by flow cytometry (mIP‐FCM). In samples from two independent donors, antigenic stimulation induced signalling proteins to join shared complexes that were observed in seven pairwise combinations among five proteins. This demonstrates that sr‐T cells isolated from small clinical samples provide sufficient material for mIP‐FCM‐based analysis of signalling‐induced protein complexes. We propose that this strategy may be useful for gaining improved mechanistic insight of sr‐T cell signal transduction associated with dermatological disease.
Sibling Conversations About Dating and Sexuality: Sisters as Confidants, Sources of Support, and Mentors
Authors: Killoren Sarah E. , Roach Andrea L.
Published: March 2014

Using an observational methodology to examine sibling communication, sisters (N = 28 dyads) were videotaped discussing their ideas about dating and sexuality. Social provision theory was used as a framework for the examination of roles enacted by sisters during these conversations. Inductive thematic analytic procedures were conducted, and three roles were identified: sisters as confidants, sources of support, and mentors. Older and younger sisters served as confidants and sources of support for one another, whereas older sisters were more likely to be mentors for their younger sisters than vice versa. Findings indicate the potential importance of sisters in the formation of adolescent girls' ideas about romantic relationships and sexuality, sibling communication as a socialization mechanism of sisters' similarities in romantic experiences and sexual behaviors/attitudes, and the inclusion of older sisters in prevention intervention programs focused on reducing adolescent sexual risk behaviors and promoting healthy romantic relationships and sexuality development.
Ethnic‐Racial Socialization and Its Correlates in Families of Black–White Biracial Children
Authors: Csizmadia Annamaria , Rollins Alethea , Kaneakua Jessica P.
Published: March 2014

Child, family, and contextual correlates of ethnic‐racial socialization among U.S. families of 293 kindergarten‐age Black–White biracial children were investigated in this study. Children with one White‐identified and one Black‐identified biological parent who were enrolled in the Early Childhood Longitudinal Study‐Kindergarten Cohort participated in this study. Parents' racial identification of children, parent age, family socioeconomic status, urbanicity, and region of country predicted the likelihood of frequent ethnic‐racial socialization. Relative to their biracially and Black‐identified peers, White‐identified biracial children were less likely to have frequent discussions about ethnic‐racial heritage. Findings suggest that ethnic‐racial socialization is a prevalent parenting practice in families of young biracial children and that its frequency varies depending on child, family, and situational factors. Implications for practice are discussed.
Relationship Quality and Depressed Affect Among a Diverse Sample of Relationally Unstable Relationship Education Participants
Authors: Bradford Angela B. , Adler‐Baeder Francesca , Ketring Scott A. , Bub Kristen L. , Pittman Joe F. , Smith Thomas A.
Published: March 2014

The association between depression and marital satisfaction has been clearly documented. Theoretical approaches describe the direction of effects as depression leading to marital dissatisfaction (stress generation model) and, alternately, marital dissatisfaction leading to depression (marital discord model). Clinical research indicates that treating the relationship of unstable couples can result in improvements in relationship satisfaction and depression. However, many unstable couples may not attend therapy and choose rather to attend Couple and Relationship Education (CRE). Using 250 ethnically diverse couples in communityCREclasses, the authors found that relationally unstable participants ofCREreport improvements in depressed affect and relationship quality after program participation. Additionally, decreased depressed affect predicted increased relationship quality, not vice versa, and there were no differences by sex. The authors note the potential value ofCREfor unstable couples and recommend that interventionists utilize an inclusive approach, devoting attention to the couple relationship as well as individual distress variables.