bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristically Late Spellings in the Hebrew Bible
Authors: Hornkohl Aaron
Published: May 2015

According to current scholarly consensus, the pre- and post-exilic strata of Biblical Hebrew differ sufficiently to allow for the relative dating of biblical texts on linguistic grounds. Challengers to this view have objected that the received orthography of the Hebrew Bible, which is fuller than that of any pre-exilic epigraphic source, shows that no pre-exilic biblical text escaped post-exilic spelling revision. Moreover, so it is claimed, susceptibility to scribal modification on the level of orthography implies susceptibility to scribal modification on the higher linguistic levels as well (i.e., phonology, morphology, syntax, lexicon), which would effectively obscure a text’s original linguistic profile. In the present article it is argued that the degree of scribal modification involved in the process of orthographical revision was not so great as to distort irremediably the picture of linguistic development seen in biblical literature, so that distinctively late linguistic features can still be distinguished from their classical counterparts. Significantly, as has been argued elsewhere, diachronic development is still discernible even in the domain of orthography, a fact demonstrated on the basis of several examples, including the spelling of the (li)qṭol-pattern qal infinitive construct.
Awakened Lord
Authors: Pellard Thomas
Published: May 2015

The native Japanese name of the Buddha hotoke < poto2ke2 has no internal etymology and is likely to be a loanword introduced together with Buddhism. The hypothesis of a link with Korean pwuche < pwuthye ‘Buddha’ and of their ultimate origin as deriving from a Chinese rendering of Sanskrit Buddha makes sense from both a linguistic and historical point of view. Still, the last part of the Japanese and Korean forms has no correspondent in Chinese and has remained unaccounted for hitherto. From the comparison with the pattern ‘Buddha-lord’ for the name of Buddha in several Asian languages, it is hypothesized that the enigmatic final element was originally a word for ‘lord, ruler, king’. This hypothesis is confirmed by the attestation of such a word in toponyms and in nobility titles recorded in ancient Chinese, Korean, and Japanese chronicles.
Herodotus’s Scythians and Ptolemy’s Central Asia: Semasiological and Onomasiological Studies. By Helmut Humbach and Klaus Faiss
Authors: Karitunen Klaus
Published: May 2015

Herodotus’s Scythians and Ptolemy’s Central Asia: Semasiological and Onomasiological Studies. By Helmut Humbach and Klaus Faiss. Wiesbaden: Dr. Ludwig Reichert Verlag, 2012. Pp. xii + 91.
Essays in Arabic Literary Biography, 925–1350. Edited by Terri DeYoung and Mary St. Germain
Authors: Boullata Issa J.
Published: May 2015

Essays in Arabic Literary Biography, 925–1350. Edited by Terri DeYoung and Mary St. Germain. Mîzân: Studien zur Literatur in der islamischen Welt, vol. 17,1. Wiesbaden: haRRaSSoWitz, 2011. Pp. vii + 371. €68.
Man of Wiles in Popular Arabic Literature: A Study of a Medieval Arab Hero. By Malcolm C. Lyons
Authors: Boullata Issa J.
Published: May 2015

The Man of Wiles in Popular Arabic Literature: A Study of a Medieval Arab Hero. By Malcolm C. Lyons. Edinburgh: Edinburgh University Press, 2012. Pp. x + 254. $105.
A new mechanism for OH vibrational relaxation leading to enhanced CO2 emissions in the nocturnal mesosphere
Authors: Sharma Ramesh D. , Wintersteiner Peter P. , Kalogerakis Konstantinos S.
Published: May 2015

On the basis of experimental and theoretical studies, this paper proposes a new mechanism that contributes to nocturnal 4.3 µm CO2 emissions. It suggests that collisions of ground state O atoms with highly vibrationally excited OH(v), produced by the reaction of H with O3, remove a substantial fraction of the OH(v) vibrational energy by a fast, spin‐allowed, multiquantum vibration‐to‐electronic energy transfer (ET) process that generates O(1D): OH(v ≥ 5) + O(3P) → OH(0 ≤ v′ ≤ v − 5) + O(1D). The electronically excited O(1D) atom is subsequently deactivated by collisions with N2 in a fast spin‐forbidden ET process that leaves the N2 molecule with an average of 2.2 vibrational quanta. Finally, the vibrational excitation of N2 is transferred by a fast, near‐resonant vibration‐to‐vibration ET process to the asymmetric stretch (v3) mode of CO2, which promptly radiates near 4.3 µm.
Depth‐variant azimuthal anisotropy in Tibet revealed by surface wave tomography
Authors: Pandey Shantanu , Yuan Xiaohui , Debayle Eric , Tilmann Frederik , Priestley Keith , Li Xueqing
Published: May 2015

Azimuthal anisotropy derived from multimode Rayleigh wave tomography in China exhibits depth‐dependent variations in Tibet, which can be explained as induced by the Cenozoic India‐Eurasian collision. In west Tibet, the E‐W fast polarization direction at depths <100 km is consistent with the accumulated shear strain in the Tibetan lithosphere, whereas the N‐S fast direction at greater depths is aligned with Indian Plate motion. In northeast Tibet, depth‐consistent NW‐SE directions imply coupled deformation throughout the whole lithosphere, possibly also involving the underlying asthenosphere. Significant anisotropy at depths of 225 km in southeast Tibet reflects sublithospheric deformation induced by northward and eastward lithospheric subduction beneath the Himalaya and Burma, respectively. The multilayer anisotropic surface wave model can explain some features of SKS splitting measurements in Tibet, with differences probably attributable to the limited back azimuthal coverage of most SKS studies in Tibet and the limited horizontal resolution of the surface wave results.
High‐resolution global magnetohydrodynamic simulation of bursty bulk flows
Authors: Wiltberger M. , Merkin V. , Lyon J. G. , Ohtani S.
Published: May 2015

A high‐resolution global magnetohydrodynamic simulation is conducted with the Lyon‐Fedder‐Mobarry (LFM) model for idealized solar wind conditions. Within the simulation results high‐speed flows are seen throughout the magnetotail when the interplanetary magnetic field (IMF) is southward. Case study analysis of these flows shows that they have an enhancement in BZ and a decrease in density preceding a peak in the flow velocity. A careful examination of the structure within the magnetotail shows that these features are driven by bursts of magnetic reconnection. In addition to the case study, a superposed epoch analysis of flows occurring during a 90 min interval of southward IMF yields statistical properties that are in qualitative agreement with observational analysis of bursty bulk flows (BBFs). For the idealized simulation conditions, the most significant differences with the observational results are a broader velocity profile in time, which becomes narrower away from the center of the current sheet, and a larger density drop after flow passage. The peak BZ amplitude is larger than in observations and precedes the peak in the flow velocity. We conclude that the LFM simulations are reproducing the statistical features of BBFs and that they are driven by spatially and temporally localized reconnection events within the simulation domain.
Determining the Minimally Important Difference in the Clinical Disease Activity Index for Improvement and Worsening in Early Rheumatoid Arthritis Patients
Authors: Curtis J. R. , Yang S. , Chen L. , Pope J. E. , Keystone E. C. , Haraoui B. , Boire G. , Thorne J. C. , Tin D. , Hitchon C. A. , Bingham C. O. , Bykerk V. P.
Published: May 2015

Objective

Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimum clinically important differences (MCID) for some measures, such as the Clinical Disease Activity Index (CDAI), have not been well‐defined in real‐world clinic settings, especially for early RA patients with low/moderate disease activity.

Methods

Data from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cut points were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self‐reported improvement or worsening. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated against patient self‐reported improvement (gold standard) and for change in pain, Health Assessment Questionnaire (HAQ), and Disease Activity Score in 28 joints (DAS28) improvement. Discrimination was examined using the area under receiver operator curves. Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity.

Results

A total of 578 patients (mean ± SD age 54.1 ± 15.3 years, 75% women, median [interquartile range] disease duration 5.3 [3.3, 8.0] months) contributed 1,169 visit pairs to the improvement analysis. The MCID cut points for improvement were 12 (patients starting in high disease activity: CDAI >22), 6 (moderate: CDAI 10–22), and 1 (low disease activity: CDAI <10). Performance characteristics were acceptable using these cut points for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units.

Conclusion

These minimum important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice.
Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry
Authors: Foeldvari Ivan , Becker Ingrid , Horneff Gerd
Published: May 2015

Objective

Uveitis is a major extraarticular quality of life–restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX).

Methods

Patients’ characteristics, treatment, and the reported first occurrence of uveitis as an adverse event were searched in the Biologics in Pediatric Rheumatology Registry. The rates per exposed patients, exposure time, and time until event were calculated.

Results

Uveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844 patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and 13 of 364 patients were receiving adalimumab. Patients with uveitis were younger (mean ± SD age 4.6 ± 4.2 versus 7.4 ± 4.5 years; P < 0.0001), more likely to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P < 0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with a uveitis diagnosis before starting treatment more often had a uveitis event (n = 28, 8.4%; OR 8.5, P < 0.0001), and more often received adalimumab (OR 2.15 [95% confidence interval 1.58–2.94], P < 0.0001). In 16 patients, a new uveitis event occurred: 11 while taking MTX (3.2 per 1,000 patient‐years), 2 while taking etanercept monotherapy (1.9 per 1,000 patient‐years), and 3 while taking etanercept and MTX combination (0.9 per 1,000 patient‐years). A new uveitis event occurred early in the disease course after a median disease duration of 1.5 years (interquartile range [IQR] 1.3–3.8) while taking etanercept and 1.8 years (IQR 1.8–2.1) for the MTX cohort. A recurrent uveitis event was reported after a disease duration of 7.6 years (IQR 4.3–10.0) in the etanercept cohort and 4.8 years (IQR 1.0–5.8) in the MTX cohort. Univariate analysis showed that MTX, but not etanercept or adalimumab, led to a lower rate of uveitis.

Conclusion

Patients with a history of uveitis had higher risks for uveitis events while taking both etanercept and adalimumab. Methotrexate turned out to be protective. Few patients developed a first uveitis event while taking etanercept, while the rate is comparable to that with MTX. Uveitis may not be attributed to be an adverse drug reaction to etanercept.
Relationship Between Medial Meniscal Extrusion and Cartilage Loss in Specific Femorotibial Subregions: Data From the Osteoarthritis Initiative
Authors: Bloecker K. , Wirth W. , Guermazi A. , Hunter D. J. , Resch H. , Hochreiter J. , Eckstein F.
Published: May 2015

Objective

Medial meniscal extrusion is known to be related to structural progression of knee osteoarthritis. However, it is unclear whether medial meniscal extrusion is more strongly associated with cartilage loss in certain medial femorotibial subregions than in others.

Methods

Segmentation of the medial tibial and femoral cartilage (baseline; 1‐year followup) and the medial meniscus (baseline) was performed in 60 participants with frequent knee pain (mean ± SD ages 61.3 ± 9.2 years, body mass index 31.3 ± 3.9 kg/m2) and with unilateral medial radiographic joint space narrowing (JSN) grades 1–3, using double‐echo steady‐state magnetic resonance images. Medial meniscal extrusion distance and extrusion area (percentage) between the external meniscal and tibial margin at baseline, and longitudinal medial cartilage loss in 8 anatomic subregions were determined.

Results

A significant association (Pearson's correlation coefficient) was seen between medial meniscal extrusion area in JSN knees and cartilage loss over 1 year throughout the entire medial femorotibial compartment. The strongest correlation was with cartilage loss in the external medial tibia (r =−0.34, P < 0.01 in JSN; r =−0.30, P = 0.02 in knees without JSN).

Conclusion

Medial meniscal extrusion was associated with subsequent medial cartilage loss. The external medial tibial cartilage may be particularly vulnerable to thinning once the meniscus extrudes and its surface is exposed to direct, nonphysiological, cartilage‐to‐cartilage contact.
Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials
Authors: Graudal Niels , Hubeck‐Graudal Thorbjørn , Faurschou Mikkel , Baslund Bo , Jürgens Gesche
Published: May 2015

Objective

The costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease‐modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA.

Methods

Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta‐analysis. These trials compared combinations of DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two reviewers independently entered data into standardized extraction forms. The combined effect measures were compared by means of the inverse variance method (continuous data) and the Mantel‐Haenszel method (dichotomous data) using a random‐effects model.

Results

The primary outcome, radiographic progression score, did not differ between the combination DMARD group and the TNF inhibitor group, neither during the second year (−0.09 units [−0.61, 0.44]) of treatment or during the first 2 years (0.66 units [−0.12, 1.43]). There were significant differences in the radiographic progression score, the American College of Rheumatology criteria for 50% improvement (ACR50), and the ACR70 response criteria at 6 months in favor of TNF inhibitor treatment, but these differences were not present in patients treated with an initial steroid course and disappeared at 24 months, irrespective of the use of steroids.

Conclusion

The difference between DMARD combination treatments, including or excluding TNF inhibitors, is small. Due to the enormous cost differences, RA guidelines should recommend combination DMARD treatment before initiation of TNF inhibitors.
Symptoms of Depression and Risk of New Episodes of Low Back Pain: A Systematic Review and Meta‐Analysis
Authors: Pinheiro Marina B. , Ferreira Manuela L. , Refshauge Kathryn , Ordoñana Juan R. , Machado Gustavo C. , Prado Lucas R. , Maher Christopher G. , Ferreira Paulo H.
Published: May 2015

Objective

To investigate the contribution of symptoms of depression to future episodes of low back pain (LBP).

Methods

A search was conducted of AMED, CINAHL, Embase, Health and Society (H&S), LILACS, MEDLINE, PsycINFO, Scopus, and Web of Science databases. We included cohort studies investigating the effect of symptoms of depression on the development of new episodes of LBP, either lifetime incidence or a recurrent episode, in a population free of LBP at baseline. We accepted the original study's definition for a new episode of LBP, and for classifying patients as LBP‐free at study entry. Two independent investigators extracted data and assessed methodological quality. Meta‐analyses with random effects were used to pool risk estimates.

Results

We included 19 studies, with 11 incorporated in the meta‐analyses. Overall pooled results showed that symptoms of depression increased the risk of developing LBP (odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.26–2.01). The risk was similar in studies that used the diagnostic interview method (OR 1.66, 95% CI 1.14–2.42) and in studies using self‐report screening questionnaires (OR 1.68, 95% CI 1.05–2.70). No statistically significant relationship was observed when we pooled studies that employed nonspecific screening questionnaires (OR 1.17, 95% CI 0.48–2.87). Three studies provided results in incremental categories of symptoms of depression and the pooled OR for the most severe level of depression (OR 2.51, 95% CI 1.58–3.99) was higher than for the lowest level (OR 1.51, 95% CI 0.89–2.56).

Conclusion

Individuals with symptoms of depression have an increased risk of developing an episode of LBP in the future, with the risk being higher in patients with more severe levels of depression.
Vitamin D Supplementation in Adolescents and Young Adults With Juvenile Systemic Lupus Erythematosus for Improvement in Disease Activity and Fatigue Scores: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Lima Glauce L. , Paupitz Juliane , Aikawa Nadia E. , Takayama Liliam , Bonfa Eloisa , Pereira Rosa M. R.
Published: May 2015

Objective

Vitamin D has an important immunomodulatory effect, but there are no trials that directly address the boosting of serum levels of 25‐hydroxyvitamin D (25[OH]D) in juvenile‐onset systemic lupus erythematosus (SLE). The aim of this study was to evaluate the effect of vitamin D supplementation on disease activity and fatigue in juvenile‐onset SLE.

Methods

This study was a randomized, double‐blind, placebo‐controlled, 24‐week trial. Forty juvenile‐onset SLE patients were randomized (1:1) to receive oral cholecalciferol 50,000 IU/week (juvenile‐onset SLE‐VitD) or placebo (juvenile‐onset SLE‐PL). Medications remained stable throughout the study. Serum levels of 25(OH)D were measured using radioimmunoassay. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measurement (ECLAM). Fatigue was assessed using the Kids Fatigue Severity Scale (K‐FSS).

Results

At baseline, groups were similar regarding age, body mass index, organ involvement, glucocorticoid dose, use of immunosuppressive drugs, SLEDAI, ECLAM, K‐FSS, and levels of 25(OH)D. After 24 weeks, the mean level of 25(OH)D was higher in the juvenile‐onset SLE‐VitD group than in the juvenile‐onset SLE‐PL group (P < 0.001). At the end of the intervention, a significant improvement in SLEDAI (P = 0.010) and in ECLAM (P = 0.006) was observed in the juvenile‐onset SLE‐VitD group compared to the juvenile‐onset SLE‐PL group. Regarding fatigue evaluation, a reduction of fatigue related to social life score was found in the juvenile‐onset SLE‐VitD group compared to the juvenile‐onset SLE‐PL group (P = 0.008). Cholecalciferol was well tolerated with no serious adverse events.

Conclusion

This study suggests that cholecalciferol supplementation for 24 weeks is effective in decreasing disease activity and improving fatigue in juvenile‐onset SLE patients.
L‐Rhamnulose‐1‐phosphate Aldolase from Thermotoga maritima in Organic Synthesis: One‐Pot Multistep Reactions for the Preparation of Imino‐ and Nitrocyclitols
Authors: Oroz‐Guinea Isabel , Hernández Karel , Camps Bres Flora , Guérard‐Hélaine Christine , Lemaire Marielle , Clapés Pere , García‐Junceda Eduardo
Published: May 2015

Rhamnulose‐1‐phosphate aldolase from Thermotoga maritima (Rhu1PATm) has been recently cloned and characterised. This hyperthermophilic enzyme offers intriguing possibilities for practical catalysis. This is due to its high stability under extreme reaction conditions, such as high temperature or the presence of organic co‐solvents. The Rhu1PATm potentiality in organic synthesis has been explored focusing on (i) the reaction stereocontrol, (ii) the possibility of combining it with other mesophilic enzymes in multienzyme systems and (iii) its application to the synthesis of imino‐ and nitrocyclitols. In our study, the diastereoselectivity of Rhu1PATm was similar to the one reported for Rhu1PA from Escherichia coli (Rhu1PAEc). However, we observed significant differences for some aldehyde acceptors. Indeed, the diastereoselectivity control was not complete, since mixtures of L‐threo (2R,3S; natural stereopreference) and D‐erythro (2R,3R) diastereoisomers were obtained as described for Rhu1PAEc. Rhu1PATm was able to catalyse aldol reactions using nitroaldehydes and N‐Cbz‐aminoaldehydes. Conversion of the selected nitroaldehydes was complete, leading to mixtures of L‐threo and D‐erythro diastereoisomers, in 95:5 and 75:25 ratios. When N‐Cbz‐aminoaldehydes were used, aldol reaction yields were lower and the stereoselectivity L‐threo:D‐erythro ranged between 32:68 to>95:5.

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Multistep Synthesis of (S)‐3‐Hydroxyisobutyric Acid from Glucose usingPseudomonas taiwanensisVLB120 B83 T7 Catalytic Biofilms
Authors: Lang Karsten , Buehler Katja , Schmid Andreas
Published: May 2015

The chiral building block (S)‐3‐hydroxyisobutyric acid [(S)‐3‐HIBA] was produced either by conversion of isobutyric acid or directly from glucose utilizing cells ofPseudomonas taiwanensisVLB120 B83 T7 as catalysts. This strain carries a point mutation in the gene encoding 3‐hydroxyisobutyrate dehydrogenase (mmsB), leading to its inactivation. The maximal specific activity in resting‐cell biotransformations using isobutyric acid as substrate was 4.9±0.4 U gcdw−1. Overexpression of the 2‐ketoisovalerate pathway genesalsS, ilvC,andilvD, and the introduction ofkivdencoding 2‐ketoacid decarboxylase resulted in the efficient fermentative synthesis of (S)‐3‐HIBA directly from glucose. Up to 22 mM (2.3 g L−1) (S)‐3‐HIBA were produced at 3.7±0.3 U gcdw−1in repeated batch experiments without observable product degradation. Utilizing a biofilm reactor it was possible to continuously produce up to 6 mM (0.63 g L−1) of (S)‐3‐hydroxyisobutyric acid with a volumetric productivity of 1.32 mmol(S)‐3‐HIBA h−1 L−1. Overall, the conversion of isobutyric acid to (S)‐3‐HIBA was found to be the rate‐limiting step, leading to the accumulation of a mixture of (S)‐3‐hydroxyisobutyric acid and isobutyric acid. This study demonstrates for the first time the production of (S)‐3‐HIBA from renewable carbon in shake flasks and biofilm reactors and sets the stage for further optimizations towards the efficient production of 3‐HIBA and its derivatives in continuous fermentations.

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A genome‐wide identified risk variant for PTSD is a methylation quantitative trait locus and confers decreased cortical activation to fearful faces
Authors: Almli Lynn M. , Stevens Jennifer S. , Smith Alicia K. , Kilaru Varun , Meng Qian , Flory Janine , Abu‐Amara Duna , Hammamieh Rasha , Yang Ruoting , Mercer Kristina B. , Binder Elizabeth B. , Bradley Bekh , Hamilton Steven , Jett Marti , Yehuda Rachel , Marmar Charles R. , Ressler Kerry J.
Published: May 2015

Genetic factors appear to be highly relevant to predicting differential risk for the development of post‐traumatic stress disorder (PTSD). In a discovery sample, we conducted a genome‐wide association study (GWAS) for PTSD using a small military cohort (Systems Biology PTSD Biomarkers Consortium; SBPBC, N = 147) that was designed as a case‐controlled sample of highly exposed, recently returning veterans with and without combat‐related PTSD. A genome‐wide significant single nucleotide polymorphism (SNP), rs717947, at chromosome 4p15 (N = 147, β = 31.34, P = 1.28 × 10−8) was found to associate with the gold‐standard diagnostic measure for PTSD (the Clinician Administered PTSD Scale). We conducted replication and follow‐up studies in an external sample, a larger urban community cohort (Grady Trauma Project, GTP, N = 2006), to determine the robustness and putative functionality of this risk variant. In the GTP replication sample, SNP rs717947 associated with PTSD diagnosis in females (N = 2006, P = 0.005), but not males. SNP rs717947 was also found to be a methylation quantitative trait locus (meQTL) in the GTP replication sample (N = 157, P = 0.002). Further, the risk allele of rs717947 was associated with decreased medial and dorsolateral cortical activation to fearful faces (N = 53, P < 0.05) in the GTP replication sample. These data identify a genome‐wide significant polymorphism conferring risk for PTSD, which was associated with differential epigenetic regulation and with differential cortical responses to fear in a replication sample. These results may provide new insight into understanding genetic and epigenetic regulation of PTSD and intermediate phenotypes that contribute to this disorder. © 2015 Wiley Periodicals, Inc.
Contrasting age related changes in autism spectrum disorder phenomenology in Cornelia de Lange, Fragile X, and Cri du Chat syndromes: Results from a 2.5 year follow‐up
Authors: Cochran Lisa , Moss Joanna , Nelson Lisa , Oliver Chris
Published: May 2015

Little is known about the way in which the characteristics of autism spectrum disorder (ASD) develop and manifest across the age span in individuals with genetic syndromes. In this study we present findings from a two and a half year follow‐up of the characteristics associated with ASD in three syndromes: Cornelia de Lange (CdLS), Fragile X (FXS), and Cri du Chat (CdCS). Parents and carers of 251 individuals (CdLS = 67, CdCS = 42, and FXS = 142) completed the Social Communication Questionnaire (SCQ) at Time 1 (T1) and again two and a half years later (T2). The FXS and CdLS groups were more likely to meet the cut‐offs for both autism and ASD and show greater severity of ASD related behaviors, at both T1 and T2, compared to the CdCS group. Older individuals (>15yrs) with CdLS were more likely to meet the cut off for ASD than younger individuals (≤ 15yrs) with the syndrome and more likely to show greater severity of social impairments. In FXS repetitive behaviors were found to become less prominent with age and in CdCS social impairments were reported to be more severe with age. There were no significant changes between T1 and T2 in the severity of ASD characteristics in the CdCS and CdLS groups. The FXS group showed significantly fewer repetitive behaviors and less severe impairments in social interaction over this time frame. The findings suggest that while there may be similarities in overall severity and presentation of ASD characteristics in CdLS and FXS, these characteristics have divergent patterns of development within these groups. © 2015 Wiley Periodicals, Inc.
Down syndrome: Cognitive and behavioral functioning across the lifespan
Authors: Grieco Julie , Pulsifer Margaret , Seligsohn Karen , Skotko Brian , Schwartz Alison
Published: May 2015

Individuals with Down syndrome (DS) commonly possess unique neurocognitive and neurobehavioral profiles that emerge within specific developmental periods. These profiles are distinct relative to others with similar intellectual disability (ID) and reflect underlying neuroanatomic findings, providing support for a distinctive phenotypic profile. This review updates what is known about the cognitive and behavioral phenotypes associated with DS across the lifespan. In early childhood, mild deviations from neurotypically developing trajectories emerge. By school‐age, delays become pronounced. Nonverbal skills remain on trajectory for mental age, whereas verbal deficits emerge and persist. Nonverbal learning and memory are strengths relative to verbal skills. Expressive language is delayed relative to comprehension. Aspects of language skills continue to develop throughout adolescence, although language skills remain compromised in adulthood. Deficits in attention/executive functions are present in childhood and become more pronounced with age. Characteristic features associated with DS (cheerful, social nature) are personality assets. Children are at a lower risk for psychopathology compared to other children with ID; families report lower levels of stress and a more positive outlook. In youth, externalizing behaviors may be problematic, whereas a shift toward internalizing behaviors emerges with maturity. Changes in emotional/behavioral functioning in adulthood are typically associated with neurodegeneration and individuals with DS are higher risk for dementia of the Alzheimer's type. Individuals with DS possess many unique strengths and weaknesses that should be appreciated as they develop across the lifespan. Awareness of this profile by professionals and caregivers can promote early detection and support cognitive and behavioral development. © 2015 Wiley Periodicals, Inc.
Biography of Nobel laureate Shuji Nakamura
Authors: Nakamura Shuji
Published: May 2015

Shuji Nakamura discovered p‐type doping in Gallium Nitride (GaN) and developed blue, green, and white “InGaN‐based” light emitting diodes (LEDs) and blue laser diodes (LDs). His inventions made possible energy efficient, solid‐state lighting systems and enabled the next generation of optical storage. In this biography, Shuji Nakamura tells the story of his personal life and his scientific career.

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Design, Synthesis, and Anti‐Inflammatory Evaluation of Novel Diphenylthiazole–Thiazolidinone Hybrids
Authors: Abdelazeem Ahmed H. , Salama Samir A. , Maghrabi Ibrahim A.
Published: May 2015

A series of diphenylthiazole–thiazolidinone hybrids was synthesized and evaluated in vitro and in vivo as anti‐inflammatory/analgesic agents. The inhibition of cyclooxygenase (COX) enzymes was suggested as a molecular mechanism for the hybrids to exert their anti‐inflammatory action. Of these compounds, 13b, 14, and 15b showed the most potent COX inhibitory activity with IC50 values between 2.03 and 12.27 µM, but with different selectivity profiles. All compounds were further evaluated in vivo for their anti‐inflammatory/analgesic activities using three animal models. Interestingly, the results of the COX assay were in agreement with those of in vivo assays where the most potent COX inhibitors, 13b, 14, and 15b, exhibited the highest anti‐inflammatory/analgesic activities compared to diclofenac. On the contrary, compounds 11 and 12 were the least potent ligands in vitro and in vivo as well.
Ability of Interleukin‐33– and Immune Complex–Triggered Activation of Human Mast Cells to Down‐Regulate Monocyte‐Mediated Immune Responses
Authors: Rivellese Felice , Suurmond Jolien , Habets Kim , Dorjée Annemarie L. , Ramamoorthi Nandhini , Townsend Michael J. , de Paulis Amato , Marone Gianni , Huizinga Tom W. J. , Pitzalis Costantino , Toes René E. M.
Published: May 2015

Objective

Mast cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). In particular, their activation by interleukin‐33 (IL‐33) has been linked to the development of arthritis in animal models. The aim of this study was to evaluate the functional responses of human mast cells to IL‐33 in the context of RA.

Methods

Human mast cells were stimulated with IL‐33 combined with plate‐bound IgG or IgG anti–citrullinated protein antibodies (ACPAs), and their effects on monocyte activation were evaluated. Cellular interactions of mast cells in RA synovium were assessed by immunofluorescence analysis, and the expression of messenger RNA (mRNA) for mast cell–specific genes was evaluated in synovial biopsy tissue from patients with early RA who were naive to treatment with disease‐modifying antirheumatic drugs.

Results

IL‐33 induced the up‐regulation of Fcγ receptor type IIa and enhanced the activation of mast cells by IgG, including IgG ACPAs, as indicated by the production of CXCL8/IL‐8. Intriguingly, mast cell activation triggered with IL‐33 and IgG led to the release of mediators such as histamine and IL‐10, which inhibited monocyte activation. Synovial mast cells were found in contact with CD14+ monocyte/macrophages. Finally, mRNA levels of mast cell–specific genes were inversely associated with disease severity, and IL‐33 mRNA levels showed an inverse correlation with the levels of proinflammatory markers.

Conclusion

When human mast cells are activated by IL‐33, an immunomodulatory phenotype develops, with human mast cells gaining the ability to suppress monocyte activation via the release of IL‐10 and histamine. These findings, together with the presence of synovial mast cell–monocyte interactions and the inverse association between the expression of mast cell genes at the synovial level and disease activity, suggest that these newly described mast cell–mediated inhibitory pathways might have a functional relevance in the pathogenesis of RA.
Effect of low frequency transcutaneous magnetic stimulation on sensory and motor transmission
Authors: Leung Albert , Shukla Shivshil , Lee Jacquelyn , Metzger‐Smith Valerie , He Yifan , Chen Jeffrey , Golshan Shahrokh
Published: May 2015

Peripheral nerve injury diminishes fast conducting large myelinated afferent fibers transmission but enhances smaller pain transmitting fibers firing. This aberrant afferent neuronal behavior contributes to development of chronic post‐traumatic peripheral neuropathic pain (PTP‐NP). Non‐invasive dynamic magnetic flux stimulation has been implicated in treating PTP‐NP, a condition currently not adequately addressed by other therapies including transcutaneous electrical nerve stimulation (TENS). The current study assessed the effect of low frequency transcutaneous magnetic stimulation (LFTMS) on peripheral sensory thresholds, nerve conduction properties, and TENS induced fast afferent slowing effect as measured by motor and sensory conduction studies in the ulnar nerve. Results indicated sham LFTMS with TENS (Sham + TENS) significantly (P = 0.02 and 0.007, respectively) reduces sensory conduction velocity (CV) and increases sensory onset latency (OL), and motor peak latency (PL) whereas, real LFTMS with TENS (Real + TENS) reverses effects of TENS on sensory CV and OL, and significantly (P = 0.036) increases the sensory PL. LFTMS alone significantly (P < 0.05) elevates sensory PL and onset‐to‐peak latency. LFTMS appears to reverse TENS slowing effect on fast conducting fibers and casts a selective peripheral modulatory effect on slow conducting pain afferent fibers. Bioelectromagnetics. 36:410–419, 2015. © 2015 Wiley Periodicals, Inc.
Core information set for oesophageal cancer surgery
Authors: Blazeby J M , Macefield R , Blencowe N S , Jacobs M , McNair A G K , Sprangers M , Brookes S T , Avery K N L , Blazeby J M , Blencowe N S , Brookes S T , Elliot J , Jacobs M , Korfage I , Macefield R , Mackichan F , Nicklin J , Smets E M A , Sprangers M A G , Strong S , Titcomb D R , van Berge Henegouwen M I , Whistance R , Witherstone J , Berrisford R , Blazeby J M , Byrne J , Dwerryhouse S , Galloway S , Griffin S M , Hassn A , Hewin D , Higgs S , Lamb P , Manson J , Moxon R , Osbourn S , Pursnani K , Shackcloth M , Underwood T , Whiting J , Williamson P
Published: May 2015

Background

Surgeons provide patients with information before surgery, although standards of information are lacking and practice varies. The development and use of a ‘core information set’ as baseline information before surgery may improve understanding. A core set is a minimum set of information to use in all consultations before a specific procedure. This study developed a core information set for oesophageal cancer surgery.

Methods

Information was identified from the literature, observations of clinical consultations and patient interviews. This was integrated to create a questionnaire survey. Stakeholders (patients and professionals) were surveyed twice to assess views on importance of information from ‘not essential’ to ‘absolutely essential’ using Delphi methods. Items not meeting predefined criteria were discarded after each survey and the final retained items were voted on, in separate patient and professional stakeholder meetings, to agree the core set.

Results

Some 67 information items were identified initially from multiple sources. Survey response rates were 76·5 per cent (185 of 242) and 54·8 per cent (126 of 230) for patients and professionals respectively (first round), and over 83 per cent in both groups thereafter. Health professionals rated short-term clinical outcomes most highly (technical complications), whereas patients prioritized information related to long-term benefits. The consensus meetings agreed the final set, which consisted of: in-hospital milestones to recovery, rates of open-and-close surgery, in-hospital mortality, major complications (reoperation), milestones in recovery after discharge, longer-term eating and drinking and overall quality of life, and chances of survival.

Conclusion

This study has established a core information set for surgery for oesophageal cancer.
Paradoxical increase in blood pressure following bilateral native nephrectomy
Authors: Ajlan Balgees A. , Safdar Osama Y. , Shalabi Mohammed , Kari Jameela A.
Published: May 2015

Key Clinical Message

Hypertension with Chronic kidney disease is often difficult to control medically. In such patients, nephrectomy can help to control blood pressure (BP). We describe a case of a 6‐year‐old boy with autosomal recessive polycystic kidney disease who showed a paradoxical increase in BP following bilateral nephrectomy.
Type‐driven data layouts for improved vectorisation
Authors: Šinkarovs Artjoms , Scholz Sven‐Bodo
Published: May 2015

Vector instructions of modern CPUs are crucially important for the performance of compute‐intensive algorithms. Auto‐vectorisation often fails because of an unfortunate choice of data layout by the programmer. This paper proposes a data layout inference for auto‐vectorisation that identifies layout transformations that convert single instruction, multiple data‐unfavourable layouts of data structures into favourable ones. We present a type system for layout transformations, and we sketch an inference algorithm for it. Finally, we present some initial performance figures for the impact of the inferred layout transformations. They show that non‐intuitive layouts that are inferred through our system can have a vast performance impact on compute intensive programs. Copyright © 2015 John Wiley & Sons, Ltd.
Preparation of longitudinal sections of hair samples for the analysis of cocaine by MALDI‐MS/MS and TOF‐SIMS imaging
Authors: Flinders Bryn , Cuypers Eva , Zeijlemaker Hans , Tytgat Jan , Heeren Ron M. A.
Published: May 2015

Matrix‐assisted laser desorption/ionization‐mass spectrometry imaging (MALDI‐MSI) for the analysis of intact hair is a powerful tool for the detection of drugs of abuse in toxicology and forensic applications. Here we present a quick, easy, and reproducible method of preparing longitudinal sections of single hairs. This method improves the accessibility of chemicals embedded in the hair matrix for molecular imaging with mass spectrometry. The images obtained from a single, sectioned hair sample show molecular distributions in the exposed medulla, cortex, and a portion of the cuticle observed as a narrow layer surrounding the cortex. Using MALDI‐MS/MS imaging, the distribution of cocaine was observed throughout five longitudinally sectioned drug‐user hair samples. The images showed the distribution of the product ion at m/z 182, derived from the precursor ion of cocaine at m/z 304. MetA‐SIMS images of longitudinally sectioned hair samples showed a more detailed distribution of cocaine at m/z 304, benzoylecgonine the major metabolite of cocaine at m/z 290 and other drugs such as methadone which was observed at m/z 310. Chronological information of drug intake can be obtained more sensitively. The chronological detail is in hours rather than months, which is of great interest in clinical as well as forensic applications. Copyright © 2015 John Wiley & Sons, Ltd.
Applying systems biology tools to study n‐butanol degradation in Pseudomonas putida KT2440
Authors: Vallon Tobias , Simon Oliver , Rendgen‐Heugle Beate , Frana Sabine , Mückschel Björn , Broicher Alexander , Siemann‐Herzberg Martin , Pfannenstiel Jens , Hauer Bernhard , Huber Achim , Breuer Michael , Takors Ralf
Published: May 2015

To smoothen the process of n‐butanol formation in Pseudomonas putida KT2440, detailed knowledge of the impact of this organic solvent on cell physiology and regulation is of outmost importance. Here, we conducted a detailed systems biology study to elucidate cellular responses at the metabolic, proteomic, and transcriptional level. Pseudomonas putida KT2440 was cultivated in multiple chemostat fermentations using n‐butanol either as sole carbon source or together with glucose. Pseudomonas putida KT2440 revealed maximum growth rates (μ) of 0.3 h−1 with n‐butanol as sole carbon source and of 0.4 h−1 using equal C‐molar amounts of glucose and n‐butanol. While C‐mole specific substrate consumption and biomass/substrate yields appeared equal at these growth conditions, the cellular physiology was found to be substantially different: adenylate energy charge levels of 0.85 were found when n‐butanol served as sole carbon source (similar to glucose as sole carbon source), but were reduced to 0.4 when n‐butanol was coconsumed at stable growth conditions. Furthermore, characteristic maintenance parameters changed with increasing n‐butanol consumption. 13C flux analysis revealed that central metabolism was split into a glucose‐fueled Entner–Doudoroff/pentose‐phosphate pathway and an n‐butanol‐fueled tricarboxylic acid cycle when both substrates were coconsumed. With the help of transcriptome and proteome analysis, the degradation pathway of n‐butanol could be unraveled, thus representing an important basis for rendering P. putida KT2440 from an n‐butanol consumer to a producer in future metabolic engineering studies.
Thermodynamic and Economic Analysis of a Coal Staged Conversion Utilization Polygeneration System
Authors: Zhang Rui
Published: May 2015

Coal polygeneration systems are recognized as promising technologies for efficient and clean coal utilization. In previous coal polygeneration systems, coal was only used as a feedstock for gasification. The value difference between diverse constituents of coal is neglected. Based on an idea to utilize the different constituents of coal separately, a coal staged conversion utilization polygeneration system is proposed. In this system, pyrolysis gas and tar are first extracted through coal pyrolysis followed by char extraction. The tar is used for fuel‐oil production through tar hydrogenation. The char is gasified to produce syngas. Pyrolysis gas and syngas are mixed together to produce methanol and electricity. Process simulation of this system was established by using Aspen Plus. For comparison, a conventional coal polygeneration system based on entrained flow gasification technology and Fischer–Tropsch synthesis technology has also been established by using Aspen Plus. Simulation results indicate that the thermal efficiency and internal rate of return of the coal staged conversion utilization polygeneration system are higher, whereas the total capital investment and discounted payback period are lower than those of the conventional coal polygeneration system. The thermal efficiency of coal staged conversion utilization polygeneration can reach 51.16 % (lower heating value).
Phthalate esters in main source water and drinking water of Zhejiang Province (China): Distribution and health risks
Authors: Wang Xiaofeng , Lou Xiaoming , Zhang Nianhua , Ding Gangqiang , Chen Zhijian , Xu Peiwei , Wu Lizhi , Cai Jianmin , Han Jianlong , Qiu Xueting
Published: May 2015

To evaluate the distributions and health risks of phthalate esters in the main source water and corresponding drinking water of Zhejiang Province, the concentrations of 16 phthalate esters in water samples from 19 sites were measured from samples taken in the dry season and wet season. The concentration of the total phthalate ester congeners in source water ranged from 1.07 μg/L to 7.12 μg/L in the wet season, from 0.01 μg/L to 1.58 μg/L in the dry season, from 1.18 μg/L to 15.28 μg/L from drinking water in the wet season, and from 0.16 μg/L to 1.86 μg/L from drinking water in the dry season. Of the 16 phthalate esters, dimethyl phthalate, dibutyl phthalate, di-(2-ethyl-hexyl) phthalate, di-iso-butyl phthalate, bis-2-n-butoxyethyl phthalate, and dicyclohexyl phthalate were present in the samples analyzed, dominated by di-iso-butyl phthalate and di-(2-ethyl-hexyl) phthalate. The concentrations of phthalate esters in the wet season were all relatively higher than those in the dry season, and the drinking water had higher concentrations of phthalate esters than source water. The phthalate ester congeners studied pose little health risk to nearby citizens. Environ Toxicol Chem 2015;34:2205–2212. © 2015 SETAC
Accumulation of contaminants of emerging concern in food crops—part 2: Plant distribution
Authors: Hyland Katherine C. , Blaine Andrea C. , Higgins Christopher P.
Published: May 2015

Arid agricultural regions often turn to using treated wastewater (reclaimed water) to irrigate food crops. Concerns arise, however, when considering the potential for persistent contaminants of emerging concern to accumulate into plants intended for human consumption. The present study examined the accumulation of a suite of 9 contaminants of emerging concern into 2 representative food crops, lettuce and strawberry, following uptake via the roots and subsequent distribution to other plant tissues. Calculating accumulation metrics (concentration factors) allowed for comparison of the compartmental affinity of each chemical for each plant tissue compartment. The root concentration factor was found to exhibit a positive linear correlation with the pH-adjusted octanol-water partition coefficient (DOW) for the target contaminants of emerging concern. Coupled with the concentration-dependent accumulation observed in the roots, this result implies that accumulation of these contaminants of emerging concern into plant roots is driven by passive partitioning. Of the contaminants of emerging concern examined, nonionizable contaminants, such as triclocarban, carbamazepine, and organophosphate flame retardants displayed the greatest potential for translocation from the roots to above-ground plant compartments. In particular, the organophosphate flame retardants displayed increasing affinity for shoots and fruits with decreasing size/octanol-water partition coefficient (KOW). Cationic diphenhydramine and anionic sulfamethoxazole, once transported to the shoots of the strawberry plant, demonstrated the greatest potential of the contaminants examined to be then carried to the edible fruit portion. Environ Toxicol Chem 2015;34:2222–2230. © 2015 SETAC