bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacists’ views on implementing a disease state management program for low back pain
Authors: Abdel Shaheed Christina , Maher Christopher G. , Williams Kylie A. , McLachlan Andrew J.
Published: February 2015

Pharmacists have the potential to take a lead role in the primary care management of people with acute low back pain. The aim of this study was to investigate pharmacists’ views on implementing a care program for people with acute low back pain in the community pharmacy. Recruitment of pharmacists for this study took place between July 2012 and March 2013. A convenience sample of 30 pharmacists who collaborated in recruiting participants for a low back pain clinical trial in Sydney (n=15 pharmacist recruiters and n=15 non-recruiters) completed an open-ended questionnaire. There was no marked variation in responses between the two groups. Participating pharmacists were receptive to the idea of implementing a care program for people with low back pain, highlighting the need for adequate reimbursement and adequate training of staff to ensure it is successful. Pharmacists identified that the follow up of people receiving such a service is dependent on several factors such as effective reminder systems and the proximity of patients to the pharmacy.
Estimating radiated flux density from wildland fires using the raw output of limited bandpass detectors
Authors: Kremens Robert L. , Dickinson Matthew B.
Published: February 2015

We have simulated the radiant emission spectra from wildland fires such as would be observed at a scale encompassing the pre-frontal fuel bed, the flaming front and the zone of post-frontal combustion and cooling. For these simulations, we developed a ‘mixed-pixel’ model where the fire infrared spectrum is estimated as the linear superposition of spectra of many (n ~ 30) greybody emitters of randomly selected areal fraction, emissivity and temperature. Our model neglects contributions from atomic and molecular line emission from combustion gasses. The purpose of these simulations was to allow unambiguous use of limited bandwidth detectors to estimate the total power emitted from a wildland fire. From the simulations we observed a well-defined relationship between ground-leaving radiance (W m–2 sr–1) and limited bandpass sensor-reaching radiance for many different detector spectral responses. Error in the relationship is least when the detector sampled in the mid-wave portion of the infrared spectrum (~3–5 μm) where flaming combustion emits most strongly. We validate our approach to estimating total power using data from experimental burns. The ability to estimate total power from limited bandpass measurements has great utility in the observation of wildland fires from ground-based instruments and aircraft and satellite platforms.
Reactivity of sorbose dehydrogenase from Sinorhizobium sp. 97507 for 1,5-anhydro-d-glucitol
Authors: Araki Toshio , Nakatsuka Tomoko , Kobayashi Fuminao , Watanabe-Ishimaru Emi , Sanada Hirokazu , Tamura Takashi , Inagaki Kenji
Published: February 2015

Purified recombinant sorbose dehydrogenase from Sinorhizobium sp. 97507 exhibited high reactivity for 1,5-anhydro-d-glucitol (1,5-AG) and l-sorbose, but little activity for the other sugars or sugar alcohols tested. Kinetic analysis revealed that its catalytic efficiency (kcat/Km) for l-sorbose and 1,5-AG is 1.8 × 102 and 1.5 × 102 s−1·M−1, respectively.
Assessing marine species vulnerability to projected warming on the Scotian Shelf, Canada
Authors: Stortini Christine H. , Shackell Nancy L. , Tyedmers Peter , Beazley Karen
Published: February 2015

Resource managers need climate adaptation tools. We build on a popular tool, the climate change vulnerability assessment (CCVA), to identify vulnerable marine species. Only warming was considered, as warming is expected to have earlier impacts in the offshore than other climate drivers, and projections of other climate drivers are not well developed. For this reason, we coin our generalized, semi-quantitative method the “Vulnerability to Projected Warming Assessment” (VPWA) as opposed to using the broader term, CCVA. We refine the typical “exposure” component to be a function of gain/loss of thermal habitat at multiple life stages. We also build on the traditional logic approach of CCVAs. We produce scores for each species, and use a null distribution through Monte Carlo simulations to identify the most vulnerable species. We evaluate the vulnerability of 33 fish and invertebrate species, on the scale of the Scotian Shelf, Canada, to two warming scenarios, mild and severe, based on regional trends and projections. At smaller spatial scales, we evaluate populations of a subset of these species. Populations in the southwest portion of the domain are found to be more vulnerable than those in the northeast. Overall, our results indicate that 45% of populations may be vulnerable under a severe (+3°C) warming scenario, including currently endangered, threatened, and commercial populations (e.g. southwestern Atlantic cod, Smooth skate, Snow crab), while only one species has a relatively high vulnerability score under the mild (+0.7°C) scenario (Moustache sculpin). Populations triaged by relative vulnerability to regional warming should help managers prioritize resources and identify knowledge gaps. For this reason, and for its biological and ecological underpinnings, our method has broad relevance within the marine science and management field. As more information become available, our VPWA can be used as a stepping-stone in the continued development of CCVA methods.
Dimethyl fumarate suppresses Theiler’s murine encephalomyelitis virus-induced demyelinating disease by modifying the Nrf2-Keap1 pathway
Authors: Kobayashi Kunitoshi , Tomiki Hiroki , Inaba Yuji , Ichikawa Motoki , Kim Byung S. , Koh Chang-Sung
Published: February 2015

Dimethyl fumarate (DMF) is a modifier of the nuclear factor (erythroid-derived 2)-2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) pathway. DMF treatment in the effector phase significantly suppressed the development of Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) both clinically and histologically. DMF treatment leads to an enhanced Nrf2 antioxidant response in TMEV-IDD mice. DMF treatment in the effector phase significantly suppressed the level of IL-17A mRNA. DMF is known to inhibit differentiation of T helper 17 (Th17) cells via suppressing NF-κB. Taken together, our data suggest that DMF treatment in the effector phase may suppress TMEV-IDD not only via enhancing the antioxidant response but also via suppressing IL-17A.
Modelling astrophysical outflows via the unified dynamo–reverse dynamo mechanism
Authors: Lingam Manasvi , Mahajan Swadesh M.
Published: February 2015

The unified dynamo–reverse dynamo (Dy-RDy) mechanism, capable of simultaneously generating large-scale outflows and magnetic fields from an ambient microscopic reservoir, is explored in a broad astrophysical context. The Dy-RDy mechanism is derived via the Hall magnetohydrodynamics, which unifies the evolution of magnetic field and fluid vorticity. It also introduces an intrinsic length-scale, the ion skin depth, allowing for the proper normalization and categorization of microscopic and macroscopic scales. The large-scale Alfvén Mach number $\mathcal {M}_{{\rm A}}$, defining the relative ‘abundance’ of the flow field to the magnetic field is shown to be tied to a microscopic scalelength that reflects the characteristics of the ambient short-scale reservoir. The dynamo (Dy), preferentially producing the large-scale magnetic field, is the dominant mode when the ambient turbulence is mostly kinetic, while the outflow producing reverse dynamo (RDy) is the principal manifestation of a magnetically dominated turbulent reservoir. It is conjectured that an efficient RDy may be the source of many observed astrophysical outflows that have $\mathcal {M}_{{\rm A}} \gg 1$.
Halocalculus aciditolerans gen. nov., sp. nov., an acid-tolerant haloarchaeon isolated from commercial salt
Authors: Minegishi Hiroaki , Echigo Akinobu , Kuwahara Ai , Shimane Yasuhiro , Kamekura Masahiro , Itoh Takashi , Ohkuma Moriya , Usami Ron
Published: February 2015

Three halophilic archaeal strains, MH2-243-1T, MH2-93-1 and MH2-91-1 were isolated from commercial salt samples from Japan, Australia, and Bolivia. Strain MH2-243-1T was able to grow in the presence of 12–30 % (w/v) NaCl (optimum, 18 % NaCl), at pH 4.5–7.0 (optimum, pH 6.0) and at 20–60 °C (optimum, 40 °C). Strains MH2-91-1 and MH2-93-1 grew in slightly different ranges. The orthologous 16S rRNA gene sequences of the three strains were almost identical (99.8–99.9 % similarities), and the closest relative was

Salarchaeum japonicum

JCM 16327T with 94.2–94.3 % 16S rRNA gene sequence similarities, followed by strains of members of the closely related genera

Halobacterium

and

Halarchaeum

. The RNA polymerase subunit B′ gene (rpoB′) sequence also showed the highest similarity (86.6 %) to that of

Salarchaeum japonicum

JCM 16327T. The DNA G+C contents of strains MH2-243-1T, MH2-93-1 and MH2-91-1 were 68.5, 68.8 and 68.3 mol%, respectively. DNA–DNA relatedness values amongst the three strains were 97–99 %. The polar lipids of the three strains were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, and at least seven unidentified glycolipids. The polar lipid composition differed from those of

Salarchaeum japonicum

and species of the genera

Halobacterium

and

Halarchaeum

. Based on the phenotypic and phylogenetic analyses, it is proposed that the isolates represent a novel species of a new genus, for which the name Halocalculus aciditolerans gen. nov., sp. nov. is proposed. The type strain of the type species is MH2-243-1T ( = JCM 19596T = KCTC 4149T) isolated from solar salt produced in Japan. MH2-93-1 ( = JCM 19595) and MH2-91-1 ( = JCM 19594) are additional strains of the type species.
Association mapping reveals the role of mutation-selection balance in the maintenance of genomic variation for gene expression
Authors: Josephs Emily B. , Lee Young Wha , Stinchcombe John R. , Wright Stephen I.
Published: February 2015

The evolutionary forces that maintain genetic variation for quantitative traits within populations remain poorly understood. One hypothesis suggests that variation is maintained by a balance between new mutations and their removal by selection and drift. Theory predicts that this mutation-selection balance will result in an excess of low-frequency variants and a negative correlation between minor allele frequency and selection coefficients. Here, we test these predictions using the genetic loci associated with total expression variation (eQTLs) and allele-specific expression variation (aseQTLs) mapped within a single population of the plantCapsella grandiflora.In addition to finding eQTLs and aseQTLs for a large fraction of genes, we show that alleles at these loci are rarer than expected and exhibit a negative correlation between phenotypic effect size and frequency. Overall, our results show that the distribution of frequencies and effect sizes of the loci responsible for local expression variation within a single, outcrossing population are consistent with mutation-selection balance.

Significance

Biologists have long sought to explain why we see genetic variation for traits in populations despite the expectation that selection will remove most variation. We address this question by using gene expression as a model trait and identifying the genetic loci that affect gene expression in a single, large population of the plantCapsella grandiflora.Alleles at loci that affect expression were rarer than expected by chance and there was a negative correlation between phenotypic effect size and frequency of these alleles. These observations are consistent with mutation-selection balance, the hypothesis that variation is maintained by a balance between new mutations and their removal by selection and drift.
ChIP-exo signal associated with DNA-binding motifs provides insight into the genomic binding of the glucocorticoid receptor and cooperating transcription factors
Authors: Starick Stephan R. , Ibn-Salem Jonas , Jurk Marcel , Hernandez Céline , Love Michael I. , Chung Ho-Ryun , Vingron Martin , Thomas-Chollier Morgane , Meijsing Sebastiaan H.
Published: February 2015

The classical DNA recognition sequence of the glucocorticoid receptor (GR) appears to be present at only a fraction of bound genomic regions. To identify sequences responsible for recruitment of this transcription factor (TF) to individual loci, we turned to the high-resolution ChIP-exo approach. We exploited this signal by determining footprint profiles of TF binding at single-base-pair resolution using ExoProfiler, a computational pipeline based on DNA binding motifs. When applied to our GR and the few available public ChIP-exo data sets, we find that ChIP-exo footprints are protein- and recognition sequence-specific signatures of genomic TF association. Furthermore, we show that ChIP-exo captures information about TFs other than the one directly targeted by the antibody in the ChIP procedure. Consequently, the shape of the ChIP-exo footprint can be used to discriminate between direct and indirect (tethering to other DNA-bound proteins) DNA association of GR. Together, our findings indicate that the absence of classical recognition sequences can be explained by direct GR binding to a broader spectrum of sequences than previously known, either as a homodimer or as a heterodimer binding together with a member of the ETS or TEAD families of TFs, or alternatively by indirect recruitment via FOX or STAT proteins. ChIP-exo footprints also bring structural insights and locate DNA:protein cross-link points that are compatible with crystal structures of the studied TFs. Overall, our generically applicable footprint-based approach uncovers new structural and functional insights into the diverse ways of genomic cooperation and association of TFs.
Structure cristalline du composé intermétallique Ni18Ge12
Authors: Kars Mohammed , Herrero Adrian Gómez , Roisnel Thierry , Rebbah Allaoua , Otero-Diáz L. Carlos
Published: February 2015

Single crystals of octadecanickel dodecagermanide were grown by chemical transport reaction. The intermetallic compound crystallizes in a superstructure of the hexagonal NiAs type (B8 type). All atoms in the asymmetric unit lie on special positions except one Ni atom (two Ni atoms have site symmetry -6.. and another one has site symmetry .2. while the Ge atoms have site symmetries 32.,m.. and 3..). In the structure, the Ni atoms are arranged in 11- or 13-vertex polyhedra (CN = 11–13). The coordination polyhedra of the Ge atoms are bicapped square antiprisms (CN = 10) or 11-vertex polyhedra (CN = 11). The structure exhibits strong Ge...Ni interactions, but no close Ge...Ge contacts are observed. The Ni atoms with CN = 13 form infinite chains along [001] with an Ni—Ni distance of 2.491 (2) Å.
Histogenesis of pure and combined Merkel cell carcinomas: An immunohistochemical study of 14 cases
Authors: Narisawa Yutaka , Koba Shinichi , Inoue Takuya , Nagase Kotaro
Published: February 2015

The histogenesis of Merkel cell carcinoma (MCC) has remained unresolved. Moreover, one of the questions is whether pure MCC and combined MCC represent the same histogenesis and entity. The existence of combined MCC suggests that MCC likely arise from pluripotent stem cells. Merkel cells (MC) localize within the bulge area, which is populated by hair follicle stem cells. We used hair follicle stem cell markers to investigate whether MCC share certain characteristics of these stem cells. Fourteen MCC specimens were examined histologically and immunohistochemically. There were six pure MCC and eight combined MCC. In six combined MCC, both MCC components and squamous components at least focally shared the expression of one or more of cytokeratin (CK)15, CK19 and CD200, which are hair follicle stem cell markers. On the other hand, four cases of pure MCC showed partially distinct CK19 expression, but did not show CK15 and/or CD200 expression. There was a distinct difference between pure MCC and combined MCC on the expression of hair follicle stem cell markers. The normal skin expressed CK15, CK19 and CD200 in the bulge area, whereas CK15 and CD200 were absent in the MC‐rich glabrous skin and touch domes. The results led us to hypothesize that combined MCC originate from the hair follicle stem cells. We postulate that combined MCC undergo multidirectional differentiation into squamous, glandular, mesenchymal and Merkel cells. Further investigation is warranted to confirm the histogenesis of pure MCC and combined MCC.
Outcomes of treatment targeting syntax production in people with Broca's‐type aphasia: evidence from psycholinguistic assessment tasks and everyday conversation
Authors: Carragher Marcella , Sage Karen , Conroy Paul
Published: February 2015

Background

Capturing evidence of the effects of therapy within everyday communication is the holy grail of aphasia treatment design and evaluation. Whilst impaired sentence production is a predominant symptom of Broca's‐type aphasia, the effects of sentence production therapy on everyday conversation have not been investigated. Given the context‐sensitive nature of spoken production by people with aphasia, it is difficult to extrapolate implications for everyday conversation based on results from task‐based assessment (such as picture description, story retell or interview). Thus, there are strong theoretical and clinical motivations to investigate generalization from sentence production treatment to everyday conversation.

Aims

To evaluate a theoretically driven treatment focused on the language production skills of participants with post‐stroke Broca's aphasia and to track outcomes from psycholinguistic assessment tasks to everyday conversation.

Methods & Procedures

A case series design was utilized with pragmatic selection of participants with chronic aphasia undergoing the same assessment and treatment procedures. Nine participants with Broca's aphasia and their main conversation partners took part in the study. Treatment was implemented once weekly over 8 weeks and targeted production of basic syntax—two, three and four constituent constructions—through principles of mapping and reduced syntax treatment. Use of different possible exemplars for nouns, particularly pronouns, was trained together with use of both light and heavy verbs. Participants had the opportunity to ‘top‐up’ therapy practise by completely a homework task that mirrored the therapy task.

Outcomes & Results

Syntactic well‐formedness was assessed in samples of constrained sentence production, narrative retell and naturally occurring conversations at baseline, 1 week post‐treatment, and 1 month post‐treatment. Treatment showed strong direct effects in trained and untrained sentence construction tasks, with some generalization to narrative retell tasks. There was little evidence of change in everyday conversation.

Conclusions & Implications

Improvement in language production in constrained assessment tasks may not impact on everyday conversations. Implications for further research are discussed, e.g. the need for bridging interventions between constrained and unconstrained contexts of language production. Clinical implications include the potential to streamline therapy planning and delivery by making use of rich, hybrid therapies to treat individuals with similar symptom profiles but with a range of underlying deficits.
Temporal information processing as a basis for auditory comprehension: clinical evidence from aphasic patients
Authors: Oron Anna , Szymaszek Aneta , Szelag Elzbieta
Published: February 2015

Background

Temporal information processing (TIP) underlies many aspects of cognitive functions like language, motor control, learning, memory, attention, etc. Millisecond timing may be assessed by sequencing abilities, e.g. the perception of event order. It may be measured with auditory temporal‐order‐threshold (TOT), i.e. a minimum time gap separating two successive stimuli necessary for a subject to report their temporal order correctly, thus the relation ‘before–after’. Neuropsychological evidence has indicated elevated TOT values (corresponding to deteriorated time perception) in different clinical groups, such as aphasic patients, dyslexic subjects or children with specific language impairment.

Aims

To test relationships between elevated TOT and declined cognitive functions in brain‐injured patients suffering from post‐stroke aphasia.

Methods & Procedures

We tested 30 aphasic patients (13 male, 17 female), aged between 50 and 81 years. TIP comprised assessment of TOT. Auditory comprehension was assessed with the selected language tests, i.e. Token Test, Phoneme Discrimination Test (PDT) and Voice‐Onset‐Time Test (VOT), while two aspects of attentional resources (i.e. alertness and vigilance) were measured using the Test of Attentional Performance (TAP) battery.

Outcomes & Results

Significant correlations were indicated between elevated values of TOT and deteriorated performance on all applied language tests. Moreover, significant correlations were evidenced between elevated TOT and alertness. Finally, positive correlations were found between particular language tests, i.e. (1) Token Test and PDT; (2) Token Test and VOT Test; and (3) PDT and VOT Test, as well as between PDT and both attentional tasks.

Conclusions & Implications

These results provide further clinical evidence supporting the thesis that TIP constitutes the core process incorporated in both language and attentional resources. The novel value of the present study is the indication for the first time in Slavic language users a clear coexistence of the ‘timing–auditory comprehension–attention’ relationships.
The Green Paradox and the importance of endogenous resource exploration
Authors: Österle Ines
Published: February 2015

It has been proposed that climate policies aimed at reducing greenhouse gas emissions from fossil fuel use may actually worsen the problem of global warming. Such a Green Paradox could occur if fossil fuel resource owners exploit their resources more rapidly due to the expectation of stricter climate policies in the future. This article shows that the emergence of the Green Paradox is less plausible if exploration activities are taken into account. An extraction model that incorporates exploration investments finds that an increasing cash flow tax is effective in dealing with climate change depending upon the specific formulation of the tax scheme. For example, the higher the initial tax level, the more effective is the tax scheme in mitigating climate change and hence a Green Paradox can be avoided. A very low growth rate is also beneficial for the climate as it leads to a small temporal redistribution of extraction to earlier periods. A very high growth rate leads to faster extraction; however, it also coincides with a significant decrease in total emissions that is inconsistent with a Green Paradox.
‘The problem here is that they want to solve everything with pills’: medication use and identity among Mainland Puerto Ricans
Authors: Adams Wallis E. , Todorova Irina L. G. , Guzzardo Mariana T. , Falcón Luis M.
Published: February 2015

Taking medications are complex symbolic acts, infused with diverse meanings regarding body and identity. This article focuses on the meanings of medications for older Puerto Ricans living on the United States mainland, a population experiencing stark health disparities. We aim to gain an understanding of the way multiple cultural and personal meanings of medications are related to and integrated in identity, and to understand how they are situated within Puerto Rican culture, history and circumstance on the US mainland. Data is drawn from thirty qualitative interviews, transcribed and translated, with older Puerto Ricans living on mainland United States. Thematic Analysis indicated four prevalent themes: embodiment of medication use; medications redefining self through the fabric of daily life; healthcare experience defined through medication; and medicine dividing the island and the mainland. While identity is impacted by experience of chronic illness, the experience of medication prescription and consumption is further related to the construction of the sense of self in distinct ways. For these individuals, medication use captures the dilemma of immigration. While cultural belonging and well‐being remains on the island of Puerto Rico, the mainland hosts both easier access to and excess reliance on medication.
Quantification of Visual Characteristics of Whipped Cream by Image Analysis and Machine Vision: Method Development
Authors: Liu Peng , Balaban Murat O.
Published: February 2015

The appearance (color, shine, surface roughness, bumpiness, view area, height) of whipped cream samples change with time. Quantitative methods based on image analysis were developed to measure these parameters in cream samples stored at 3 temperatures (room temperature, 10 °C and 2 °C) for up to 24 h. There was a small decrease in L* and a* values over time, and a significant increase in b* values. ΔE values suggest that these color changes are significant and observable (2.96 for room temperature, 9.46 for 10 °C, 12.6 for 2 °C). Difference between polarized and nonpolarized images was used to quantify shine. The length of a laser line over the cream sample was measured to quantify the change in bumpiness of the surface (33.8%, 41.78%, and 33.27% reduction in laser line length for room temperature, 10 °C, and 2 °C, respectively). For room temperature stored samples, most changes occurred during the first 5 min. For samples stored at 10 °C and 2 °C, most changes occurred during the first 30 min. Turn angles data did not provide useful information. The changes in view area depended on temperature: at room temperature the area increased over time, at 10 °C it increased first then decreased; at 2 °C the view area decreased over time. Correlation of the results of these methods with sensory evaluation can make the evaluation of the appearance of whipped cream more objective, repeatable, and quantitative.
Temporal distributions and environmental adaptations of two types of multicellular magnetotactic prokaryote in the sediments of Lake Yuehu, China
Authors: Du Hai‐jian , Chen Yi‐ran , Zhang Rui , Pan Hong‐miao , Zhang Wen‐yan , Zhou Ke , Wu Long‐fei , Xiao Tian
Published: February 2015

Two morphotypes (spherical and ellipsoidal) of multicellular magnetotactic prokaryotes (MMPs) have been reported from the sediments of Lake Yuehu, China. Here, their temporal distributions and their relationships with biogeochemical parameters are studied. Samples were collected at approximately 2‐week intervals from two sites (A and B) during the period September 2012 to December 2013. The abundance of MMPs was high in summer and autumn, but low in winter and spring. Furthermore, the peaks in the numbers of the two types of MMPs were sequential, with the highest concentration of the spherical MMPs occurring prior to that of the ellipsoidal MMPs. This may be related to different optimal growth temperatures for the two types. Although the two types of MMP coexisted at both sites, their numbers were different; at most times, spherical MMPs dominated at site A, whereas ellipsoidal MMPs dominated at site B. Geochemical analysis revealed that the environmental conditions at site A varied more than at site B. Compared with the widely distributed spherical MMPs, ellipsoidal MMPs seemed to prefer more stable habitats. This is the first report of the temporal distribution of ellipsoidal MMPs in sediments, suggesting that their environmental adaptations differ from those of spherical MMPs.
In aged mice, low surrogate light chain promotes pro‐B‐cell apoptotic resistance, compromises the PreBCR checkpoint, and favors generation of autoreactive, phosphorylcholine‐specific B cells
Authors: Ratliff Michelle , Alter Sarah , McAvoy Kelly , Frasca Daniela , Wright Jacqueline A. , Zinkel Sandra S. , Khan Wasif N. , Blomberg Bonnie B. , Riley Richard L.
Published: February 2015

In aged mice, new B‐cell development is diminished and the antibody repertoire becomes more autoreactive. Our studies suggest that (i) apoptosis contributes to reduced B lymphopoiesis in old age and preferentially eliminates those B‐cell precursors with higher levels of the surrogate light chain (SLC) proteins (λ5/VpreB) and (ii) λ5low B‐cell precursors generate new B cells which show increased reactivity to the self‐antigen/bacterial antigen phosphorylcholine (PC). Pro‐B cells in old bone marrow as well as pro‐B cells from young adult λ5‐deficient mice are resistant to cytokine‐induced apoptosis (TNFα; TGFβ), indicating that low λ5 expression in pro‐B cells is sufficient to cause increased survival. Transfer of TNFα‐producing ‘age‐associated B cells’ (ABC; CD21/35− CD23−) or follicular (FO) B cells from aged mice into RAG‐2 KO recipients led to preferential loss of λ5high pro‐B cells, but retention of λ5low, apoptosis‐resistant pro‐B cells. In old mice, there is increased reactivity to PC in both immature bone marrow B cells and mature splenic FO B cells. In young mice, absence of λ5 expression led to a similar increase in PC reactivity among bone marrow and splenic B cells. We propose that in old age, increased apoptosis, mediated in part by TNFα‐producing B cells, results in preferential loss of SLChigh pro‐B cells within the bone marrow. Further B‐cell development then occurs via an ‘SLClow’ pathway that not only impairs B‐cell generation, but promotes autoreactivity within the naïve antibody repertoires in the bone marrow and periphery.
Global analyses revealed age‐related alterations in innate immune responses after stimulation of pathogen recognition receptors
Authors: Metcalf Talibah U. , Cubas Rafael A. , Ghneim Khader , Cartwright Michael J. , Grevenynghe Julien Van , Richner Justin M. , Olagnier David P. , Wilkinson Peter A. , Cameron Mark J. , Park Byung S. , Hiscott John B. , Diamond Michael S. , Wertheimer Anne M. , Nikolich‐Zugich Janko , Haddad Elias K.
Published: February 2015

Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG‐I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro‐inflammatory and antiviral cytokines and chemokines including TNFα, IL‐6, IL‐1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up‐regulation of PD‐L1 on monocytes and T cells, and increased expression of PD‐L2 and B7‐H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR‐stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T‐cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age‐associated changes in cytokine, chemokine and interferon production, as well as co‐stimulatory protein expression could contribute to the blunted memory B‐ and T‐cell immune responses to vaccines and infections.
Association of Monocyte Chemoattractant Protein‐1 (MCP‐1)‐2518A>G Polymorphism with Susceptibility to Coronary Artery Disease: A Meta‐Analysis
Authors: Bai Xiao‐Yan , Li Shujing , Wang Miao , Qu Xinjian , Hu Gaolei , Xu Zhaowei , Chen Min , He Guo‐Wei , Wu Huijian
Published: February 2015

We attempted to systematically elucidate the association between monocyte chemoattractant protein‐1 (MCP‐1) ‐2518A>G polymorphism and risk of coronary artery disease (CAD). Eligible studies were identified through PubMed, EBSCO, and Web of Science Databases. The magnitude of MCP‐1 polymorphism effect and its possible mode of action on CAD were estimated. The odds ratio (OR) with 95% confidence intervals (CI) were pooled in a specific genetic model to assess the association. A total of 21 studies were involved. There was significant gene effect on CAD risk in the overall population (likelihood ratio test: p < 0.0001). Patients with GG and AG genotypes had 1.435 (95% CI: 1.183–1.740) and 1.087 (95% CI: 1.008–1.172) times higher risk of CAD than those with AA genotype. These gene effects suggested a recessive model to be appropriate. The pooled OR was 1.362 (95% CI: 1.137–1.631; puncorrected = 0.001, pFDR = 0.005) in the recessive model. In the ethnicity‐stratified analysis, significant association was observed in the Caucasian population (OR = 1.492; 95% CI: 1.106–2.014; puncorrected = 0.009, pFDR = 0.015), whereas no statistical significant association was detected in the Asian population (adjusted p = 0.124). The results suggested that MCP‐1 ‐2518A>G polymorphism may be associated with susceptibility to CAD, especially in Caucasians.
Theophylline Pharmacokinetics in Foetal Sheep: Maternal Metabolic Capacity is the Principal Driver
Authors: DuBois Barent , Louey Samantha , Giraud George D. , Cherala Ganesh , Jonker Sonnet S.
Published: February 2015

Understanding theophylline pharmacokinetics (PK) in the foetus is essential to prevent in utero toxicity and optimize prophylactic therapies. Previous studies in pregnancy have been obfuscated by maternal dosing and inadequate sampling in the foetus; both render modelling of foetal PK difficult. Six ewes carrying singleton foetuses received theophylline (60 mg) into the foetal jugular vein. Blood samples were drawn from the foetus and ewe over 36 hr. Serum concentrations were measured. Maternal and foetal pharmacokinetic parameters were estimated. Foetal non‐compartmental pharmacokinetic parameters were as follows: half‐life 7.37 ± 1.22 hr; volume of distribution 44.62 ± 11.45 L; area under the curve 14.82 ± 2.71 hr/(μg/mL); and clearance 4.15 ± 0.70 L/hr. Rapid theophylline distribution across the placenta was observed. Maternal non‐compartmental pharmacokinetic parameters were as follows: half‐life 6.54 ± 2.44 hr; volume of distribution 32.48 ± 9.99 L; area under the curve 16.28 ± 4.53 hr/(μg/mL); and clearance 3.69 ± 1.47 L/hr. Foetal and ewe serum concentration–time profiles were fit together into a 3‐compartment population pharmacokinetic model, and parameters were as follows: central volume 1.38 ± 0.11 L; 2nd peripheral compartment volume 3.11 ± 0.29 L; 3rd peripheral compartment volume 60.14 ± 6.02 L; elimination clearance 9.89 ± 0.90 L/hr; distribution clearance between central and 2nd compartment 30.87 ± 2.31 L/hr; and distribution clearance between 2nd and 3rd compartments 13.89 ± 1.11 L/hr. Cytochrome P4501A expression was robust in maternal liver; negligible activities were observed in placenta, foetal liver and foetal kidney. In vitro protein binding of theophylline was 30% lower in foetal serum compared to maternal serum (29.7 ± 4.4 versus 42.0 ± 3.6%‐bound). Free concentrations were lower in the foetus than in the ewe, suggesting active transport across placenta. In summary, foetal clearance of theophylline is attributable to rapid distribution into the maternal circulation across the placenta followed by greater maternal protein binding and metabolic activity.
One of few or one of many: Social identification and psychological well‐being among minority youth
Authors: Bratt Christopher
Published: February 2015

Feeling belongingness with small social groups such as the family or a group of friends predicts psychological well‐being. Acculturation research has argued for similar effects of belongingness with large social groups. In particular, a strong ethnic identity is assumed to improve psychological well‐being among members of minority groups, but this conclusion has been drawn based on cross‐sectional data. This study uses three‐wave longitudinal data collected among adolescents from ethnic minority groups (N = 705), comparing identification with small groups (the family and the school class) with identification with large groups (the ethnic in‐group and the nation) as predictors of psychological well‐being (self‐esteem, mental health problems, and life satisfaction). Analyses suggest that identification with small groups, in particular with the family, can predict developments in psychological well‐being (self‐esteem and mental health). In contrast, the data gave no support for causal effects from ethnic identity or national identity, in spite of substantial bivariate correlations with all three dimensions in psychological well‐being. The findings have implications for acculturation research. In particular, research on ethnic or national identity as predictors of psychological well‐being will benefit from adding small‐group identities as covariates and using longitudinal data.
Preschool‐Age Problem Behavior and Teacher–Child Conflict in School: Direct and Moderation Effects by Preschool Organization
Authors: Skalická Věra , Belsky Jay , Stenseng Frode , Wichstrøm Lars
Published: February 2015

The hypothesis was tested that the new open‐group Norwegian day‐care centers would more than traditionally organized centers negatively affect (a) current and (b) future teacher–child relationships, and (c) the developmental legacy of preschool problem behavior. The focus was on eight hundred and fifty 4‐year‐olds from 153 centers who were followed up in first grade. Results of this natural quasi‐experiment revealed that children from open‐group centers (a) experienced less teacher–child closeness in preschool and (b) more teacher–child conflict in first grade, and (c) that high levels of preschool problem behavior forecast especially high levels of future teacher–child conflict, but only for children from open‐group centers. Results highlight the importance of spatial and social organization of day care and their translational implications.
Defining early mycosis fungoides: validation of a diagnostic algorithm proposed by the International Society for Cutaneous Lymphomas
Authors: Vandergriff Travis , Nezafati Kaveh A. , Susa Joseph , Karai Laszlo , Sanguinetti Amy , Hynan Linda S. , Ambruzs Josephine M. , Oliver Dwight H. , Pandya Amit G.
Published: February 2015

Background

Mycosis fungoides (MF) is the most common subtype of cutaneous T‐cell lymphoma and is often difficult to diagnose. Early‐stage disease is particularly challenging and requires clinical and histopathologic correlation to make an accurate diagnosis. In order to facilitate the diagnosis of early MF, an algorithm has been proposed by the International Society for Cutaneous Lymphomas (ISCL) whereby clinical and histopathologic characteristics as well as immunohistochemistry and T‐cell receptor gene rearrangement studies may be applied to suspected cases of MF. The diagnostic utility of this algorithm has not yet been validated. We sought to determine the validity of the proposed algorithm via an investigator‐blinded, retrospective, case‐control study.

Methods

A total of 34 cases were randomly selected from the database of a clinic for cutaneous T‐cell lymphomas and included patients with MF and patients with clinicopathologic mimics. The proposed diagnostic algorithm was systematically applied to the entire cohort. Each case was assigned a composite score based on the parameters in the proposed algorithm.

Results

Among the 24 cases of MF, 21 cases achieved four or more points through application of the algorithm. Among the 10 cases of MF mimics, only four achieved four or more points. This difference was significant (Fisher's exact test, p = 0.009). The sensitivity of the 4‐point threshold for a diagnosis of MF was 87.5% and the specificity was 60%.

Conclusions

The diagnostic algorithm proposed by the ISCL is a statistically valid method for defining cases of early MF and distinguishing these cases from other benign dermatoses. However, the clinical utility of the algorithm may be limited by its low specificity. Further refinement of the algorithm may improve its accuracy.
Histologische Merkmale granulomatöser Hauterkrankungen: Teil 1: nichtinfektiöse granulomatöse Erkrankungen
Authors: Tronnier Michael , Mitteldorf Christina
Published: February 2015

Granulomatöse Hauterkrankungen gehören zu einer heterogenen Gruppe, bei denen mit Ausnahme der infektiös induzierten Granulome und der Fremdkörpergranulome über die Ätiopathogenese wenig bekannt ist. Die Kenntnis der histomorphologischen Veränderungen ist für das Verständnis des klinischen Bildes und des Krankheitsverlaufes von grofler Bedeutung.
Mindfulness‐Based Psychoeducation for Parents of Children With Attention‐Deficit/Hyperactivity Disorder: An Applied Clinical Project
Authors: Anderson Sarah B. , Guthery Ann M.
Published: February 2015

Topic

Attention‐deficit/hyperactivity disorder (ADHD) affects more than 5 million American children; the likelihood of their parents experiencing stress is high, which may lead to negative outcomes. Mindful parenting is a parent training modality that teaches compassion, listening, and creative engagement with one's child, and has been shown to be effective in decreasing levels of parental stress.

Purpose

An 8‐week evidence‐based applied clinical project (N = 7) was designed to answer the question: In parents of children with the diagnosis of ADHD, or exhibiting ADHD traits, what is the effect of providing mindful parenting psychoeducation in addition to standard of care treatment on levels of parental stress post intervention?

Sources Used

An exhaustive literature search was performed using the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, Psyc‐INFO, and PubMed.

Conclusions

Outcomes were measured using the Parenting Stress Index, Fourth Edition Short Form (PSI‐4‐SF). Scores on the Total Stress scale decreased significantly after 8 weeks (p = .018); a significant decrease also occurred across two of the three PSI‐4‐SF subscales (Parental Distress and Parent‐Child Dysfunctional Interaction). Recommendations for practice change, suggestions for future clinical inquiry, and project limitations are discussed.
Preschool irritability predicts child psychopathology, functional impairment, and service use at age nine
Authors: Dougherty Lea R. , Smith Victoria C. , Bufferd Sara J. , Kessel Ellen , Carlson Gabrielle A. , Klein Daniel N.
Published: February 2015

Background

Little is known about the predictive validity and clinical significance of chronic irritability during early childhood. This prospective, longitudinal study examined associations of preschool chronic irritability with psychiatric disorders, functional impairment, and service use at age nine in a large community sample.

Methods

Four hundred and forty‐six children were assessed at age three and again at age nine. Child psychopathology and functional impairment were assessed at age three with the Preschool Age Psychiatric Assessment (PAPA) with parents and at age nine with the Kiddie‐Schedule of Affective Disorders and Schizophrenia (K‐SADS) with parents and children. Items from the PAPA were used to create a dimensional measure of chronic irritability at age three. At age nine, mothers, fathers, and youth completed the Child Depression Inventory (CDI) and the Screen for Anxiety Related Disorders (SCARED).

Results

Chronic irritability at age three predicted any current and lifetime anxiety disorders at age nine, current and lifetime generalized anxiety disorder, and current separation anxiety, after controlling for baseline anxiety disorders. In addition, preschool irritability predicted increases in anxiety and disruptive behavior disorder symptoms on the K‐SADS, and maternal and paternal reports of depressive and anxiety symptoms on the CDI and SCARED. Lastly, preschool irritability predicted greater functional impairment and outpatient treatment use, even after controlling for all psychiatric disorders at baseline.

Conclusions

Findings underscore the central role of irritability in developmental psychopathology and support the importance of early detection and interventions targeting preschool irritability.
On the potential strength and consequences for nonrandom gene flow caused by local adaptation in flowering time
Authors: Weis A. E.
Published: February 2015

Gene flow is generally considered a random process, that is the loci under consideration have no effect on dispersal success. Edelaar and Bolnick (Trends Ecol Evol, 27, 2012 659) recently argued that nonrandom gene flow could exert a significant evolutionary force. It can, for instance, ameliorate the maladaptive effects of immigration into locally adapted populations. I examined the potential strength for nonrandom gene flow for flowering time genes, a trait frequently found to be locally adapted. The idea is that plants that successfully export pollen into a locally adapted resident population will be a genetically biased subset of their natal population – they will have resident‐like flowering times. Reciprocally, recipients will be more migrant‐like than the resident population average. I quantified the potential for biased pollen exchange among three populations along a flowering time cline in Brassica rapa from southern California. A two‐generation line cross experiment demonstrated genetic variance in flowering time, both within and among populations. Calculations based on the variation in individual flowering schedules showed that resident plants with the most migrant‐like flowering times could expect to have up to 10 times more of the their flowers pollinated by immigrant pollen than the least migrant‐like. Further, the mean flowering time of the pollen exporters that have access to resident mates differs by up to 4 weeks from the mean in the exporters’ natal population. The data from these three populations suggest that the bias in gene flow for flowering time cuts the impact on the resident population by as much as half. This implies that when selection is divergent between populations, migrants with the highest mating success tend to be resident‐like in their flowering times, and so, fewer maladaptive alleles will be introduced into the locally adapting gene pool.
Police and Military as Good Strangers
Authors: Klein Gary , Klein Helen Altman , Lande Brian , Borders Joseph , Whitacre James C.
Published: February 2015

The objective of this project was to understand why and how some police officers and military personnel are more effective than others at managing civilian encounters without creating hostility – ‘Good Strangers’ (GSs). We conducted cognitive task analysis (CTA) interviews with 17 US police officers and 24 US warfighters (Marines and Army soldiers). The interviews yielded a total of 38 incidents (17 police and 21 military), which we used to identify critical skills for functioning as GSs. These skills centred on having a sensemaking frame that established a professional identity as a GS – Someone who seeks opportunities to increase civilian trust in police/military. This frame requires skills in gaining voluntary compliance, building rapport, trading off security and other frames versus trust building, and taking the perspective of civilians.

Practitioner points

To work effectively with civilians, police and military personnel need to use a Good Stranger frame, which casts each encounter as an opportunity to build trust.

This GS frame requires skills such as trading off security to be seen as trustworthy, perspective taking, gaining rapport, gaining voluntary compliance rather than coercive compliance, and de‐escalating tense situations.

The GS frame may be surprisingly easy to acquire for some police and military; observation of role models and their effectiveness seems to be a powerful training opportunity. Other training leverage points involve peer pressure, becoming more effective at gaining civilian cooperation, and recognizing the problems created by failing to build trust.