bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and acceptability of sodium picosulphate/magnesium citrate vs low‐volume polyethylene glycol plus ascorbic acid for colon cleansing: a randomized controlled trial
Authors: Manes G. , Amato A. , Arena M. , Pallotta S. , Radaelli F. , Masci E.
Published: April 2013

Aim

The study compared the efficacy, safety and tolerability of a low‐volume picosulphate/magnesium citrate preparation with that of polyethylene glycol plus ascorbic acid (PEG + ASC) in a randomized clinical trial (RCT).

Method

A multicentre randomized, single‐blinded study was designed. Adult outpatients undergoing colonoscopy received either picosulphate/magnesium citrate (Group 1) or PEG + ASC (Group 2). Bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS) and rated as adequate if ≥ 2 in each segment. Patient acceptance, satisfaction and related symptoms were recorded.

Results

Two‐hundred and eighty‐five patients were included. Preparation was adequate in 75.7% of patients in Group 1 and in 76.5% of patients in Group 2. The mean BBPS scores for the entire colon and for the right colon were comparable between groups. In addition, 97.1% patients in Group 1 and 84.8% in Group 2 reported no or mild discomfort (P < 0.0003) and 97.8% and 83.4% expressed their willingness to repeat the preparation (P < 0.0001). Palatability was better in Group 1, whereas related symptoms occurred more frequently in Group 2. Regardless of which preparation was used, the split regimen was associated with better cleansing compared with the same‐day method (OR = 3.39; 95% CI: 1.1–10.4; P = 0.03). Other predictors of poor cleansing were comorbidity, discomfort during preparation and incomplete (< 75%) preparation.

Conclusion

Both picosulphate/magnesium citrate and PEG + ASC are effective for bowel preparation. Tolerability and palatability are better for picosulphate/magnesium citrate. A split schedule is associated with higher cleansing quality also for low‐volume regimens.
Specific analysis of KIT and PDGFR‐alpha expression and mutational status in Merkel cell carcinoma
Authors: Swick Brian L. , Srikantha Rupasree , Messingham Kelly N.
Published: April 2013

Background

The purpose of this study was to explore the immunohistochemical and mutational status of the tyrosine kinases KIT and platelet derived growth receptor‐alpha (PDGFRA) in Merkel cell carcinoma (MCC). Specifically, we examined the mutated exons in gastrointestinal stromal cell tumors that may confer a treatment response to imatinib mesylate.

Methods

We evaluated KIT and PDGFRA immunostaining in 23 examples of MCC utilizing laser capture microdissection to obtain pure samples of tumor genomic DNA from 18 of 23 examples of MCC. PCR amplification and sequencing of KIT exons 9, 11, 13 and 17, and PDGFRA exons 10, 12, 14 and 18 for mutations was performed.

Results

Fifteen of 23 tumors (65%) demonstrated CD117 expression and 22 of 23 tumors (95%) demonstrated PDGFRA expression. A single heterozygous KIT exon 11 base change resulting in an E583K mutation was discovered in 12 of 18 (66%) examples of MCC. In addition, a single nucleotide polymorphism was detected in eight of 18 tumors (44%) in exon 18 of PDGFRA (codon 824; GTC > GTT).

Conclusions

We discovered a novel somatic KIT exon 11 E583K mutation in 66% of tumors. This mutation has been previously described in a human with piebaldism and appears to represent an inactivating mutation. Therefore, despite expression of CD117 and PDGFRA, the absence of activating mutations in these tyrosine kinases makes KIT and PDGFRA unlikely candidates of MCC oncogenesis.
Cutaneous presentation of chronic lymphocytic leukemia as unique extramedullar involvement in a patient with normal peripheral blood lymphocyte count (monoclonal B‐cell lymphocytosis)
Authors: Tapia Gustavo , Mate José‐Luis , Fuente María‐José , Navarro José‐Tomás , Fernández‐Figueras Maria‐Teresa , Juncà Jordi , Ferrándiz Carlos , Ariza Aurelio
Published: April 2013

Skin infiltration by chronic lymphocytic leukemia (CLL) is very rare and almost all reported cases occur in advanced stage. We report a patient with no relevant past medical history who presented with cutaneous erythematous plaques. A punch biopsy showed typical CLL morphologic and immunophenotypic features. Subsequent studies revealed a normal lymphocyte count in peripheral blood, and there was no evidence of lymphadenopathy or organomegaly. Flow cytometry demonstrated a clonal B‐cell population both in the bone marrow and peripheral blood (1.60 × 109/l) with a CLL phenotype, but it did not fulfill required criteria for CLL diagnosis. Without cutaneous involvement, this case should be classified as monoclonal B‐cell lymphocytosis.
Atypical generalized eruptive histiocytosis clonally related to chronic myelomonocytic leukemia with loss of Y chromosome
Authors: Shon Wonwoo , Peters Margot S. , Reed Kurtis B. , Ketterling Rhett P. , Dogan Ahmet , Gibson Lawrence E.
Published: April 2013

Generalized eruptive histiocytosis, described in 1963 by Winklemann and Muller, is a reactive, self‐healing form of non‐Langerhans histiocytosis. Rare cases of atypical generalized eruptive histiocytosis have been reported in patients with hematopoietic malignancy, but the biological relationship between the two disorders is not known. We report an 84‐year‐old man with chronic myelomonocytic leukemia who presented with coalescing erythematous papules and plaques on the posterior neck, ear and lower lip, followed by development of blast crisis. Skin biopsy revealed a thick band‐like dermal infiltrate of cells that exhibited morphologic features of macrophages or histiocytes and prominent elastolytic phagocytosis. These cells demonstrated a mature immunophenotype, expressing CD14 and CD68, with partial expression of CD13 but not CD1a, CD43, CD56, CD123, Langerin, or S‐100 protein. Karyotype and fluorescence in situ hybridization analyses showed loss of the Y chromosome in bone marrow and skin specimens, providing evidence of a clonal relationship between the cutaneous eruption and the underlying chronic myelomonocytic leukemia. The presence of the same clone in skin and bone marrow specimens from our patient supports the possibility that atypical generalized eruptive histiocytosis is a marker for underlying hematopoietic malignancy. Discovery of additional cases may shed further light on the pathogenesis of this rare entity.
Primary cutaneous CD4 positive small/medium T‐cell lymphoma with high proliferation index and CD30‐positive large lymphoid cells
Authors: Zhang Ling , Shao Haipeng
Published: April 2013

Primary cutaneous CD4 positive small/medium pleomorphic T‐cell lymphoma (SMPTCL) represents a provisional subtype of primary cutaneous T‐cell lymphoma with indolent clinical course. A few aggressive fatal cases with increased proliferation rate and few infiltrating CD8 positive T‐cells have been reported. We describe a case of SMPTCL with an increased proliferation rate, admixed CD30‐positive large lymphoid cells, and few infiltrating CD8 positive T‐cells. The lymphoma cells were positive for CD3, CD4, CD2 and CD5, and negative for CD8. A subset of the lymphoma cells was positive for follicular helper T‐cell markers bcl‐6 and PD‐1. There were approximately 20% CD30‐positive large lymphoid cells, and Ki‐67 showed a moderately high proliferation rate (∼40%), mostly in the large lymphoid cells. CD8 infiltrating T‐cells were few (<5%). The patient had an indolent disease with complete response to radiation therapy. To the best of our knowledge, this is the first reported case of SMPTCL with an increased proliferation rate and large CD30+ cells that followed an indolent clinical course.
Long‐term survival in elderly patients with stable coronary disease
Authors: Ruiz Ortiz Martín , Ogayar Cristina , Romo Elías , Mesa Dolores , Delgado Mónica , Anguita Manuel , Castillo Juan C. , Arizón José M. , Suárez de Lezo José
Published: April 2013

Background

This study aimed to assess long‐term prognosis of stable coronary artery disease (sCAD) in patients aged ≥ 75 years and to identify clinical predictors of cardiovascular and overall mortality.

Materials and Methods

From February 2000 to January 2007, 391 outpatients aged ≥ 75 years (median 78 years, interquartile range [IQR] 76–81 years, 66% male) with sCAD were recruited in this prospective cohort study. Associations of baseline variables with long‐term cardiovascular and all‐cause death were investigated.

Results

After up to 11 years of follow‐up (median 4 years, IQR 2–6 years), 89 patients died (23%, 5·45%/year), 35 from cardiovascular causes (9%, 2·14%/year). Multivariate analysis identified family history of coronary disease (HR 4·28, 95% CI 1·22–15·02, P = 0·02), baseline atrial fibrillation (HR 3·18, 95% CI 1·37–7·39, P = 0·007), age (HR 1·61 per 5 year increase, 95% CI 1·04–2·50, P = 0·03), resting heart rate (HR 1·26 per 5 bpm increase, 95% CI 1·09–1·47, P = 0·003) and previous revascularization (HR 0·17, 95% CI 0·04–0·77, P = 0·02) as independent predictors of cardiovascular death, and previous acute coronary syndrome (HR 4·93, 95% CI 1·49–16·30, P = 0·009), baseline atrial fibrillation (HR 1·96, 95% CI 1·12–3·43, P = 0·02), tobacco use (HR 1·69, 95% CI 1·00–2·84, P = 0·049 for ex‐smoking and HR 6·78, 95% CI 0·89–51·47, P = 0·06 for active smoking), age (HR 1·58 per 5 year increase, 95% CI 1·18–2·11, P = 0·002), resting heart rate (HR 1·10 per 5 bpm increase, 95% CI 1·00–1·22, P = 0·05) and diastolic blood pressure (HR 0·97, 95% CI 0·94–0·99, P = 0·01) as independent predictors of overall mortality.

Conclusions

In this study, 4‐years overall mortality was 23% among elderly patients with sCAD. Simple clinical variables can identify patients at higher risk of mortality.
A review of continuing professional development for dentists in Europe*
Authors: Barnes E. , Bullock A. D. , Bailey S. E. R. , Cowpe J. G. , Karaharju‐Suvanto T.
Published: April 2013

Aim:  To summarise findings from a literature review of dentists’ engagement in continuing professional development (CPD) and its effects on improving oral health care for patients.

Method:  The search strategy used key terms in a range of databases and an academic literature search engine, complemented by hand searching and citation follow‐up.

Results:  One hundred and fourteen papers were reviewed. The majority of dentists engaged in CPD. Factors affecting participation included time since graduation, costs, work and home commitments, postgraduate qualification, interest and convenience. Learning needs identification and reflection on practice were rarely evidenced. Common modes of CPD were courses and journal reading; no one delivery method proved more effective. Few papers directly explored recommendations for topics although suggestions related to common areas of error and gaps in knowledge or skill. Studies of CPD effectiveness and impact‐on‐practice suggested that courses can result in widespread new learning and considerable self‐reported change in practice. However, significant barriers to implementing change in workplace practice were noted and included availability of materials, resources and support from colleagues.

Conclusion:  To ensure high standards of care, alongside recommending core or mandatory topics, more attention should be given to reflection on learning needs, the learner’s readiness to engage with education and training and the influence of the workplace environment.
Acquisition of t(11;14) in a patient with chronic lymphocytic leukemia carrying both t(14;19)(q32;q13.1) and +12
Authors: Nishida Yuhki , Takeuchi Kengo , Tsuda Kenji , Ugai Tomotaka , Sugihara Hiroki , Yamakura Masayuki , Takeuchi Masami , Matsue Kosei
Published: April 2013

A rare recurrent chromosomal translocation, t(14;19)(q32;q13), has been identified in a variety of B‐cell malignancies, including chronic lymphocytic leukemia (CLL). We report a unique case of CLL in a patient carrying both trisomy 12 and t(14;19) (q32;q13.1), in whom t(11;14)(q13;q32) developed at relapse. The patient was a 77‐yr‐old woman, and her lymphoma cells at presentation showed CD5+, CD10−, CD19+, CD20+(dim), CD23+, CD38+, and CD11c+. At relapse, the patient's lymphoma cells showed positive staining for cyclin D1 in addition to CD5, CD20, and CD23. Lymphoma cells in specimens at both presentation and relapse were positive for lymphoid enhancer factor 1 (LEF1) and negative for sex‐determining region Y‐box 11 (SOX11). IGH‐BCL1 FISH became positive at relapse. Split FISH assay using BCL1, BCL3, IGH, and CCND1 probes on lymph node specimens obtained at presentation and at autopsy confirmed that the translocation of BCL3 was solely detected in the lymph node at presentation and detected BCL3 and CCND1 translocations in the specimen at autopsy. These observations indicated that IGH‐BCL3 and IGH‐CCND1 had occurred in the same clone after treatment of the disease. In line with immunohistochemical and cytogenetic studies, additional PCR analysis of the FR3‐JH region showed the same sequence derived from IGHV4‐34 in specimens obtained at disease onset and relapse.
Effect of splenectomy on iron balance in patients with β‐thalassemia major: a long‐term follow‐up
Authors: Casale Maddalena , Cinque Patrizia , Ricchi Paolo , Costantini Silvia , Spasiano Anna , Prossomariti Luciano , Minelli Salvatore , Frega Valeria , Filosa Aldo
Published: April 2013

Objective

A retrospective study was performed to explore the effect of splenectomy on iron balance in thalassemia major (TM).

Methods

Twenty two TM patients treated with splenectomy were compared with a control group (non‐splenectomized patients) matched for sex, age, pretransfusional Hb, chelation therapy, and duration of follow‐up in a retrospective study to evaluate blood consumption, iron intake, and serum ferritin during an overall observation period of 6 yrs before and 10 yrs after splenectomy.

Results

Splenectomy improved parameters of iron balance, determining a significant reduction in blood consumption (P < 0.01), iron intake (P < 0.01), and serum ferritin (P < 0.01). Comparing the two groups, blood consumption and iron intake were similar in presplenectomy period (P > 0.05), but serum ferritin was significantly higher in splenectomized patients (P < 0.01). After splenectomy, blood consumption and iron intake were significantly lower (P < 0.01) in splenectomized group while serum ferritin did not differ significantly (P > 0.05) between two groups, except for the first year (P < 0.05).

Conclusion

Splenectomy determines immediate drop in blood consumption and iron intake but slow downtrend of ferritin; direct measurements of iron overload, such as magnetic resonance studies, are needed to better understand the effect of splenectomy on iron balance parameters. Tailoring chelation therapy and eventually its intensification seem more efficient measures to manage iron accumulation in TM and to lower iron level to safety threshold.
Serum hepcidin levels and muscle iron proteins in humans injected with low‐ or high‐dose erythropoietin
Authors: Robach Paul , Recalcati Stefania , Girelli Domenico , Campostrini Natascia , Kempf Tibor , Wollert Kai C. , Corbella Michela , Santambrogio Paolo , Perbellini Luigi , Brasse‐Lagnel Carole , Christensen Britt , Moutereau Stéphane , Lundby Carsten , Cairo Gaetano
Published: April 2013

Inhibition of hepcidin expression by erythropoietic signals is of great physiological importance; however, the inhibitory pathways remain poorly understood. To investigate (i) the direct effect of erythropoietin (Epo) and (ii) the contribution of putative mediators on hepcidin repression, healthy volunteers were injected with a single dose of Epo, either low (63 IU/kg, n = 8) or high (400 IU/kg, n = 6). Low‐dose Epo provoked hepcidin down‐modulation within 24 h; the effect was not immediate as hepcidin circadian variations were still present following injection. High‐dose Epo induced no additional effect on the hepcidin response, that is hepcidin diurnal fluctuations were not abolished in spite of extremely high Epo levels. We did not find significant changes in putative mediators of hepcidin repression, such as transferrin saturation, soluble transferrin receptor, or growth differentiation factor 15. Furthermore, the potential hepcidin inhibitor, soluble hemojuvelin, was found unaltered by Epo stimulation. This finding was consistent with the absence of signs of iron deficiency observed at the level of skeletal muscle tissue. Our data suggest that hepcidin repression by erythropoietic signals in humans may not be controlled directly by Epo, but mediated by a still undefined factor.
Clarifying Ethical Intuitionism
Authors: Cowan Robert
Published: April 2013

In recent years there has been a resurgence of interest inEthicalIntuitionism, whose core claim is thatnormal ethical agents can and do have non‐inferentially justified first‐order ethical beliefs. Although this is the standard formulation, there are two senses in which it is importantly incomplete. Firstly, ethical intuitionism claims that there are non‐inferentially justified ethical beliefs, but there is a worrying lack of consensus in the ethical literature as to what non‐inferentially justified belief is. Secondly, it has been overlooked that there are plausibly differenttypesof non‐inferential justification, and that accounting for the existence of a specific sort of non‐inferential justification is crucial for any adequate ethical intuitionist epistemology. In this context, it is the purpose of this paper to provide an account of non‐inferentially justified belief which is superior to extant accounts, and, to give a refined statement of the core claim of ethical intuitionism which focuses on the type of non‐inferential justification vital for a plausible intuitionist epistemology. Finally, it will be shown that the clarifications made in this paper make it far from obvious that two intuitionist accounts, which have received much recent attention, make good on intuitionism's core claim.
Tropospheric ozone reduces carbon assimilation in trees: estimates from analysis of continuous flux measurements
Authors: Fares Silvano , Vargas Rodrigo , Detto Matteo , Goldstein Allen H. , Karlik John , Paoletti Elena , Vitale Marcello
Published: April 2013

High ground‐level ozone concentrations are typical of Mediterranean climates. Plant exposure to this oxidant is known to reduce carbon assimilation. Ozone damage has been traditionally measured through manipulative experiments that do not consider long‐term exposure and propagate large uncertainty by up‐scaling leaf‐level observations to ecosystem‐level interpretations. We analyzed long‐term continuous measurements (>9 site‐years at 30 min resolution) of environmental and eco‐physiological parameters at three Mediterranean ecosystems: (i) forest site dominated by Pinus ponderosa in the Sierra Mountains in California, USA; (ii) forest site composed of a mixture of Quercus spp. and P. pinea in the Tyrrhenian sea coast near Rome, Italy; and (iii) orchard site of Citrus sinensis cultivated in the California Central Valley, USA. We hypothesized that higher levels of ozone concentration in the atmosphere result in a decrease in carbon assimilation by trees under field conditions. This hypothesis was tested using time series analysis such as wavelet coherence and spectral Granger causality, and complemented with multivariate linear and nonlinear statistical analyses. We found that reduction in carbon assimilation was more related to stomatal ozone deposition than to ozone concentration. The negative effects of ozone occurred within a day of exposure/uptake. Decoupling between carbon assimilation and stomatal aperture increased with the amount of ozone pollution. Up to 12–19% of the carbon assimilation reduction in P. ponderosa and in the Citrus plantation was explained by higher stomatal ozone deposition. In contrast, the Italian site did not show reductions in gross primary productivity either by ozone concentration or stomatal ozone deposition, mainly due to the lower ozone concentrations in the periurban site over the shorter period of investigation. These results highlight the importance of plant adaptation/sensitivity under field conditions, and the importance of continuous long‐term measurements to explain ozone damage to real‐world forests and calculate metrics for ozone‐risk assessment.
Experimental determination of CePO4 and YPO4 solubilities in H2O–NaF at 800°C and 1 GPa: implications for rare earth element transport in high‐grade metamorphic fluids
Authors: Tropper P. , Manning C. E. , Harlov D. E.
Published: April 2013

Monazite (CePO4) and xenotime (YPO4) are important accessory minerals in metasediments. They host significant rare earth elements (REE) and are useful for geochronology and geothermometry, so it is essential to understand their behavior during the metasomatic processes that attend high‐grade metamorphism. It has been proposed that F‐bearing fluids enhance solubility and mobility of REE and Y during high‐grade metamorphism. We assessed this possibility by determining the solubility of synthetic CePO4 and YPO4 crystals in H2O–NaF fluids at 800°C and 1 GPa. Experiments used hydrothermal piston‐cylinder and weight‐loss methods. Compared to the low solubilities of CePO4 and YPO4 in pure H2O (0.04 ± 0.04 and 0.25 ± 0.04 millimolal, respectively), our results indicate an enormous increase in the solubility of both phosphates with increasing NaF concentration in H2O: CePO4 solubility reaches 0.97 molal in 20 mol.% NaF, and YPO4 shows an even stronger solubility enhancement to 0.45 molal in only 10 mol.% NaF. The greatest relative solubility increases occur at the lowest NaF concentration. The solubilities of CePO4 and YPO4 show similar quadratic dependence on NaF, consistent with possible dissolution reactions of: CePO4 + 2NaF =  CeF2+ + Na2PO4− and YPO4 + 2NaF = YF2+ + Na2PO4−. Solubilities of both REE phosphates are significantly greater in NaF than in NaCl at equivalent salt concentration. A fluid with 10 mol.% NaCl and multiply saturated with fluorite, CePO4, and YPO4 would contain 1.7 millimolal Ce and 3.3 millimolal Y, values that are respectively 2.1–2.4 times greater than in NaCl‐H2O alone. The results indicate that Y, and by extension heavy rare earth elements (HREE), can be fractionated from LREE in fluorine‐bearing saline brines which may accompany granulite‐facies metamorphism. The new data support previous indications that REE/Y mobility at these conditions is enhanced by complexing with F in the aqueous phase.
Geochemical simulations to assess the fluorine origin in Sierra de Gador groundwater (SE Spain)
Authors: Daniele L. , Corbella M. , Vallejos A. , Díaz‐Puga M. , Pulido‐Bosch A.
Published: April 2013

Sierra de Gádor is a complex, Triassic age aquifer system formed by dolostones and limestones with interbedded gypsum. On top, a thick Neogene‐Quaternary series gives rise to shallow aquifers. F‐Pb‐Zn stratabound deposits are found within the Triassic carbonate formations. Their mineral paragenesis includes sphalerite, galena, pyrite, marcasite, fluorite and barite. The Sierra de Gádor groundwater is the principal water resource for this semiarid environment, and the population is potentially exposed to hazardous elements related to mining activities and wastes. In October 1966, an intensive precipitation event (190 mm day−1) broke several old tailing structures, flooding part of the Berja village with polluted sludge. Fluorine values in some boreholes and springs were found higher than 1.5 mg l−1, the maximum value permitted by Spanish regulation for human consumption. Hydrogeochemistry data, statistical tools and geochemical simulations were used in this study to assess the physicochemical processes and the fluorine sources within this carbonate aquifer. Most of the analysed water samples are close to equilibrium with respect to carbonate minerals but are undersaturated with respect to fluorite and gypsum. About 39% of the samples have fluorine concentration higher than the regulatory limit. A statistical analysis indicates that fluorine has a low correlation with other variables. Inverse and mixing models, performed with the code PHREEQC, differentiate the predominance of water–rock interaction processes within the carbonate aquifer and water mixing between the carbonate and shallow aquifers. The results indicate that some fluorite dissolution must occur in the carbonate Triassic aquifer, whereas the shallow aquifers leach fluorine from mining wastes. Both types of aquifers are interconnected, and their waters mix below the flooded area. There, the high fluorine values appear to have two sources: (i) the regional fluorine enrichment due to the mineralization; and (ii) the polluted 1966 flood that reached the deep carbonates via the shallow aquifer.
Interleukin‐33 exacerbates acute colitis via interleukin‐4 in mice
Authors: Pushparaj Peter N. , Li Dong , Komai‐Koma Mousa , Guabiraba Rodrigo , Alexander James , McSharry Charles , Xu Damo
Published: April 2013

Interleukin‐33 (IL‐33) and its receptor ST2 are over‐expressed in clinical colitis tissue. However, the significance of these observations is at present unknown. Significantly, we demonstrate here that IL33 and ST2 are the primary early genes induced in the inflamed colon of BALB/c mice following dextran sulphate sodium (DSS)‐induced experimental ulcerative colitis. Accordingly diarrhoea and DSS‐induced colon inflammation were impaired in ST2−/− BALB/c mice and exacerbated in wild‐type mice by treatment with exogenous recombinant IL‐33, associated respectively with reduced and enhanced expression of chemokines (CXCL9 and CXCL10), and inflammatory (IL‐4, IL‐13, IL‐1, IL‐6, IL‐17) and angiogenic (vascular endothelial growth factor) cytokines in vivo. The exacerbation effect of treatment with recombinant IL‐33 on DSS‐induced acute colitis was abolished in IL‐4−/− BALB/c mice. Hence, IL‐33 signalling via ST2, by inducing an IL‐4‐dependent immune response, may be a major pathogenic factor in the exacerbation of ulcerative colitis.
Indomethacin inhibits eosinophil migration to prostaglandin D2: therapeutic potential of CRTH2 desensitization for eosinophilic pustular folliculitis
Authors: Kataoka Naoko , Satoh Takahiro , Hirai Aiko , Saeki Kazumi , Yokozeki Hiroo
Published: April 2013

Indomethacin is a cyclo‐oxygenase inhibitor, and shows therapeutic potential for various eosinophilic skin diseases, particularly eosinophilic pustular folliculitis. One of the unique characteristics of indomethacin is that, unlike other non‐steroidal anti‐inflammatory drugs, it is a potent agonist of chemoattractant receptor‐homologous molecule expressed on T helper type 2 cells (CRTH2), a receptor for prostaglandin D2 (PGD2). This study investigated the pharmacological actions of indomethacin on eosinophil migration to clarify the actual mechanisms underlying the therapeutic effects of indomethacin on eosinophilic pustular folliculitis. Eosinophils exhibited chemokinetic and chemotactic responses to both PGD2 and indomethacin through CRTH2 receptors. Pre‐treatment of eosinophils with indomethacin greatly inhibited eosinophil migration to PGD2 and, to a much lesser extent, to eotaxin (CCL11); these effects could be mediated by homologous and heterologous desensitization of eosinophil CRTH2 and CCR3, respectively, by agonistic effects of indomethacin on CRTH2. Indomethacin also cancelled a priming effect of Δ12‐PGJ2, a plasma metabolite of PGD2, on eosinophil chemotaxis to eotaxin. Indomethacin down‐modulated cell surface expression of both CRTH2 and CCR3. Hair follicle epithelium and epidermal keratinocytes around eosinophilic pustules together with the eccrine apparatus of palmoplantar lesions of eosinophilic pustular folliculitis were immunohistochemically positive for lipocalin‐type PGD synthase. Indomethacin may exert therapeutic effects against eosinophilic skin diseases in which PGD2‐CRTH2 signals play major roles by reducing eosinophil responses to PGD2.
Parental Speech at 6 Months Predicts Joint Attention at 12 Months
Authors: Roberts Siwan , Fyfield Rhiannon , Baibazarova Eugenia , van Goozen Stephanie , Culling John F. , Hay Dale F.
Published: April 2013

In a prospective longitudinal study of a representative community sample (N = 264), mothers' references to infants' mental states were coded during a topic‐sharing task in the home at 6 months. Joint attention behaviour was assessed in the laboratory at 12 months. Individual joint attention skills (gaze following, gaze alternating, and declarative pointing) were significantly inter‐correlated, with a single factor accounting for 68% of the variance. Mothers' references to infants' mental states at 6 months predicted infants' joint attention at 12 months. The association was not explained by sociodemographic characteristics of the family, the mother's mental state, or by the quantity or acoustic properties of her speech. However, variability in pitch of maternal speech was an independent predictor of the infants' later joint attention skills. Taken together, these findings suggest that mothers' infant‐directed speech fosters infants' attentive participation in topic‐sharing interactions, which in turn provide an important arena in which joint attention skills develop over the first year of life.
STRATEGY GAGA
Authors: Anderson Jamie , Reckhenrich Jörg , Kupp Martin
Published: April 2013

Jamie Anderson, Jörg Reckhenrich and Martin Kupp celebrate strategy the Lady Gaga way.
TRANSFORMING THE MISSING MIDDLE
Authors: Anderson‐Macdonald Stephen
Published: April 2013

Roughly two billion people in the world live on $2 a day or less. Of these a staggering 50 per cent are estimated to be micro entrepreneurs, running a small business to make ends meet but employing only a handful of people. If just a small proportion of these entrepreneurs were encouraged to grow and invest in their business, and hire more employees, it could transform the fortunes of the developing economies, and billions of people living in poverty. But how? It is a challenge that Stephen Anderson‐Macdonald is hoping to help tackle.
THINK AGAIN: AVOIDING DECISION DEBACLES
Authors: Nutt Paul C.
Published: April 2013

When a leader decides to launch a major project that is sure to attract public scrutiny — such as opening a new amusement park or building a new international airport — the result is too often far from what was promised in the original press release. The resulting debacle often draws a great deal of attention to the decision‐maker. In this BSR article from 2001, Paul C. Nutt reveals why such debacles happen.
Perfect High‐Temperature Plasticity Realized in Multiwalled Carbon Nanotube‐Concentrated α‐Al2O3 Hybrid
Authors: Estili Mehdi , Sakka Yoshio , Wu Wen‐Wen , Nishimura Toshiyuki , Yoshida Hidehiro , Kawasaki Akira
Published: April 2013

We investigate the high‐temperature compressive deformation behavior of a novel, fully dense and structurally uniform, 20 vol% multiwalled carbon nanotube (MWCNT)–α‐Al2O3 matrix hybrid, which has a strong room‐temperature interfacial shear resistance (ISR) and a unique MWCNT‐concentrated grain‐boundary (GB) structure. We realized a perfect plastic deformation at 1400°C and a rather high initial strain rate of 10−4 s−1 by a low ~30 MPa flow stress, which is contrary to the strain hardening response of fine‐grain monolithic Al2O3. This unique performance in CNT–ceramic system in compression is explained as follows: the concentrated network of individual MWCNTs perfectly withstands the high‐temperature and shear/compressive forces, and strongly preserves the nanostructure of Al2O3 matrix by preventing the dynamic grain growth, even during a large ~44% deformation. Furthermore, the presence of large amount of radially soft/elastic, highly energy‐absorbing MWCNTs in the GB and specially multiple junction areas, and a potentially weak 1400°C‐ISR, could greatly facilitate the GB sliding process (despite the hybrid's strong room‐temperature ISR), as evidenced by the formation of some submicrometer‐scale MWCNT aggregates in GB area, the equiaxed grains and dislocation‐free nanostructure of the deformed hybrid. The results presented here could be attractive for the ceramic forming industry and could be regarded as a reference for oxide systems in which, the GB areas are occupied with soft/elastic, highly energy‐absorbing nanostructures.
Effects of education of paediatric patients undergoing elective surgical procedures on their anxiety – a systematic review
Authors: Copanitsanou Panagiota , Valkeapää Kirsi
Published: April 2013

Aims and objectives

To identify and critically appraise studies addressing the implementation of education for children aged 2–12 years undergoing elective surgical procedures and to determine whether education is associated with improvements in children's anxiety and other emotions.

Background

Children undergoing surgery often experience anxiety, which may lead to negative health outcomes, such as increased pain, feeding difficulties and sleeping problems. Education of children about their condition according to their individual needs may be correlated with reduced anxiety.

Design

Systematic review.

Methods

A database search in MEDLINE, PsycInfo, Cochrane Library and CINAHL was carried out during February 2011. Using the PICOS acronym, the query was organised into a searchable foreground question: the studies should evaluate (Objective) the effects of education (Intervention) compared with the standard preparation (Control) for children aged 2–12 years old undergoing elective surgeries (Population). The results would be based on randomised controlled studies (Study design). In total, 475 articles were yielded, from which 45 full‐text articles were assessed for eligibility, and finally, 16 studies were included in the review.

Results

In 12 of the 16 studies, children in the education groups reported lower anxiety scores. In two studies, no statistically significant effect of education was reported on anxiety. Moreover, education had an age‐related effect in two studies, by being more effective to children older than four to six years and having a negative effect on younger children's anxiety. Parents of children in the education groups experienced lower anxiety.

Conclusions

Education seems to be especially effective in the reduction in older children's anxiety and to have a negative effect on younger children's anxiety.

Relevance to clinical practice

Education can be incorporated into the care provided to children aged four to six years or older undergoing elective surgical procedures, according to their individualised needs.
Patient experience with bedpans in acute care: a cross‐sectional study
Authors: Gattinger Heidrun , Werner Birgit , Saxer Susi
Published: April 2013

Aims and objectives

To describe individual experiences of patients using the bedpan in an acute care setting.

Background

Patients describe the use of the bedpan often as uncomfortable and painful, and nurses mention difficulties using standard‐sized bedpans for obese patients or removing a bedpan without soiling the bed. Although the bedpan is still regularly used in hospitals, there are few empirical studies that confirm these experiences.

Design

A descriptive quantitative research design.

Methods

A convenience sample of 78 patients was recruited, and data were collected using a standardised questionnaire (German version of the Bedpan Ongemak Schaal). Descriptive statistics were used to analyse frequency (scale A) and extent of inconvenient experiences (scale B). Internal consistency of the scales was tested using Cronbach's alpha.

Results

A major finding of the study was that most patients felt dependent on other persons and no autonomous movement was possible on the bedpan. Patients were frequently confronted with pain, inconvenient characteristics of the bedpan (e.g. coldness, hardness), uncomfortable positions and hygiene inconveniences (e.g. wet backside, fear that urination may miss the bedpan).

Conclusion

As the bedpan is still regularly used in acute care hospitals, innovations in bedpan models are necessary to address the problems. But there are also several courses of action nurses should consider when caring for patients who are dependent on the bedpan.

Relevance for clinical practice

The discomfort of the bedpan, the feeling of dependency and embarrassment could lead to undesirable patient reactions, such as avoidance of fluid intake or leaving the bed. If nurses know the reasons for this behaviour, they could meet these problems with empathetic understanding.
Wittgenstein, Religious “Passion,” and Fundamentalism
Authors: Plant Bob
Published: April 2013

Notwithstanding his own spiritual inadequacies, Wittgenstein has a profound respect for those capable of living a genuinely religious life; namely, those whose “passionate,” “loving” faith demands unconditional existential commitment. In contrast, he disapproves of those who see religious belief as hypothetical, reasonable, or dependent on empirical evidence. Drawing primarily on Culture and Value, “Lectures on Religious Belief,” and On Certainty, in this essay I defend two claims: (1) that there is an unresolved tension between Wittgenstein's later descriptive‐therapeutic approach and the implicit normativity of his conception of genuine/passionate religious belief; and (2) that the demarcation between the latter and its pseudo‐religious counterpart is itself problematic. To illustrate these claims I argue that apocalyptic Christian fundamentalism presents a significant challenge to Wittgenstein's taxonomy. Despite these shortcomings, however, I conclude by suggesting that his characterization of religious belief as a “passion” or “love” remains valuable.
Medical Manichaeism
Authors: Campbell Austin L.
Published: April 2013

Medical discourse in the contemporary United States is rife with military metaphors. These metaphors have come under vigorous criticism over the last few decades but to no avail; the militaristic tendency has proven tenacious. This essay suggests that its tenacity stems, at least in part, from a dualistic understanding of medicine unaddressed by prior criticisms. For an alternative, this essay turns to Augustine of Hippo, balancing close readings of works that deal explicitly with medical themes—The Catholic Way of Life and the Manichean Way of Life (De moribus) and The Nature of the Good (De natura boni)—with a constructive approach. By adapting Augustine's privative account of evil, we can understand disease as a condition of loss and treatment as a task of restoration. This reconfiguration shifts the focus of our interpretive discourses from malicious invaders to a fuller affirmation of the lived experiences of those who are ill.
Re‐embedding Moral Agency
Authors: Steck Christopher
Published: April 2013

The connection between ethics and theological vision has become increasingly important for ethics as we better appreciate how the moral agent is embedded in a framework that affectively and intellectually shapes her moral reasoning. Moral reasoning is always reasoning within (that is, within a moral framework, a religious worldview, and/or a set of ideological commitments). A similar framing occurs in literature, which I refer to as its “horizon.” A literary text's horizon comprises the theological and metaphysical commitments that are implied by the text and that the reader relies on to make sense of it. I suggest that there is a parallel between how moral frameworks and literary horizons operate in that both shape moral judgment. I argue that in using literature as a resource for ethics, the same contemporary currents that have led us to appreciate the embeddedness of moral reasoning should also encourage us to give more careful attention to the theological or metaphysical vision implied by a text. Such a “theo‐ethical” reading of literature provides a richer understanding of particular moral goods and the interplay between those goods and ethical themes like agency, hope, and redemption. I substantiate this claim with a reading of William Blake's Jerusalem: The Emanation of the Giant Albion.
Effects of incremental amounts of fish oil on trans fatty acids and Butyrivibrio bacteria in continuous culture fermenters
Authors: AbuGhazaleh A. A. , Ishlak A.
Published: April 2013

Previous studies have shown that adding fish oil (FO) to ruminant animal diets increased vaccenic acid (VA; t11 C18:1) accumulation in the rumen. Therefore, the objective of this study was to evaluate the effect of dietary FO amounts on selected strains of rumen bacteria involved in biohydrogenation. A single‐flow continuous culture system consisting of four fermenters was used in a 4 × 4 Latin square design with four 9 days consecutive periods. Treatment diets were as follows: (i) control diet (53:47 forage to concentrate; CON), (ii) control plus FO at 0.5% (DM basis; FOL), (iii) control plus FO at 2% (DM basis; FOM) and (iv) control plus FO at 3.5% (DM basis; FOH). Fermenters were fed treatment diets three times daily at 120 g/day. Samples were collected from each fermenter on day 9 of each period at 1.5, 3 and 6 h post‐morning feeding and then composited into one sample per fermenter. Increasing dietary FO amounts resulted in a linear decrease in acetate and isobutyrate concentrations and a linear decrease in acetate‐to‐propionate ratio. Propionate, butyrate, valerate and isovalerate concentrations were not affected by FO supplementation. Concentrations of C18:0 in fermenters linearly decreased, while concentrations of t10 C18:1 and VA linearly increased as dietary FO amounts increased. The concentrations of c9t11 and t10c12 conjugated linoleic acid were not affected by FO supplementation. The DNA abundance for Butyrivibrio fibrisolvens, Butyrivibrio vaccenic acid subgroup, Butyrivibrio stearic acid subgroup and Butyrivibrio proteoclasticus linearly decreased as dietary FO amounts increased. In conclusion, FO effects on trans fatty acid accumulation in the rumen may be explained in part by FO influence on Butyrivibrio group.
The effect of orally administered epigallocatechin‐3‐gallate on ligature‐induced periodontitis in rats
Authors: Cho A.‐R. , Kim J.‐H. , Lee D.‐E. , Lee J.‐S. , Jung U.‐W. , Bak E.‐J. , Yoo Y.‐J. , Chung W.‐G. , Choi S.‐H.
Published: April 2013

Background and Objective

Epigallocatechin‐3‐gallate (EGCG) is known for its beneficial properties, including anti‐inflammatory and anti‐oxidative activities. Recently, reports have suggested that EGCG plays a pivotal role in regulating cytokine expression and osteoclastic activity. In the present study, we investigated whether orally administered EGCG has a therapeutic effect on ligature‐induced periodontitis.

Materials and Methods

Forty‐eight Sprague–Dawley rats were treated with EGCG or phosphate‐buffered saline. Periodontitis was induced by tying a ligature for 7 d. After removing ligation, EGCG (200 mg/kg) or phosphate‐buffered saline was administered via oral gavage on a daily basis. Rats were killed after 1, 2 and 4 wk of administration. Histologic and histomorphometric analyses, tartrate resistant acid phosphatase staining and immunohistochemistry were carried out.

Results

In the control group, bone loss did not recover even after the causative factor of periodontitis was eliminated. On the other hand, distance from cemento‐enamel junction to alveolar bone crest, long junctional epithelium and collagen destruction were reduced in the EGCG group. Decreased interleukin (IL)‐6 expression was shown from the early stage of EGCG administration, followed by reduced tumor necrosis factor (TNF) expression at week 4 EGCG group. The CT area showed a higher decrease of IL‐6 expression between the control and EGCG group than alveolar bone area. Downregulation of TNF and IL‐6 expression led to a decrease in osteoclast number and activity, which resulted in reduced bone loss.

Conclusions

Systemic administration of EGCG could have a therapeutic effect on damaged periodontal tissue. Inhibited cytokine expression, including TNF and IL‐6 is responsible for the reduction in osteoclast formation, osteoclastic activity and collagen destruction.
An autopsy case of preclinical multiple system atrophy (MSA‐C)
Authors: Kon Tomoya , Mori Fumiaki , Tanji Kunikazu , Miki Yasuo , Wakabayashi Koichi
Published: April 2013

Multiple system atrophy (MSA) is divided into two clinical subtypes: MSA with predominant parkinsonian features (MSA‐P) and MSA with predominant cerebellar dysfunction (MSA‐C). We report a 71‐year‐old Japanese man without clinical signs of MSA, in whom post mortem examination revealed only slight gliosis in the pontine base and widespread occurrence of glial cytoplasmic inclusions in the central nervous system, with the greatest abundance in the pontine base and cerebellar white matter. Neuronal cytoplasmic inclusions (NCIs) and neuronal nuclear inclusions (NNIs) were almost restricted to the pontine and inferior olivary nuclei. It was noteworthy that most NCIs were located in the perinuclear area, and the majority of NNIs were observed adjacent to the inner surface of the nuclear membrane. To our knowledge, only four autopsy cases of preclinical MSA have been reported previously, in which neuronal loss was almost entirely restricted to the substantia nigra and/or putamen. Therefore, the present autopsy case of preclinical MSA‐C is considered to be the first of its kind to have been reported. The histopathological features observed in preclinical MSA may represent the early pattern of MSA pathology.
Expression of an Arabidopsis molybdenum cofactor sulphurase gene in soybean enhances drought tolerance and increases yield under field conditions
Authors: Li Yajun , Zhang Jiachang , Zhang Juan , Hao Ling , Hua Jinping , Duan Liusheng , Zhang Mingcai , Li Zhaohu
Published: April 2013

LOS5/ABA3 gene encoding molybdenum cofactor sulphurase is involved in aldehyde oxidase (AO) activity in Arabidopsis, which indirectly regulates ABA biosynthesis and increased stress tolerance. Here, we used a constitutive super promoter to drive LOS5/ABA3 overexpression in soybean (Glycine max L.) to enhance drought tolerance in growth chamber and field conditions. Expression of LOS5/ABA3 was up‐regulated by drought stress, which led to increasing AO activity and then a notable increase in ABA accumulation. Transgenic soybean under drought stress had reduced water loss by decreased stomatal aperture size and transpiration rate, which alleviated leaf wilting and maintained higher relative water content. Exposed to drought stress, transgenic soybean exhibited reduced cell membrane damage by reducing electrolyte leakage and production of malondialdehyde and promoting proline accumulation and antioxidant enzyme activities. Also, overexpression of LOS5/ABA3 enhanced expression of stress‐up‐regulated genes. Furthermore, the seed yield of transgenic plants is at least 21% higher than that of wide‐type plants under drought stress conditions in the field. These data suggest that overexpression of LOS5/ABA3 could improve drought tolerance in transgenic soybean via enhanced ABA accumulation, which could activate expression of stress‐up‐regulated genes and cause a series of physiological and biochemical resistant responses.
Genetic modulation of the iris transillumination defect: a systems genetics analysis using the expanded family of BXD glaucoma strains
Authors: Swaminathan Shankar , Lu Hong , Williams Robert W. , Lu Lu , Jablonski Monica M.
Published: April 2013

We investigated the contributions of Tyrp1 and Gpnmb to the iris transillumination defect (TID) in five age cohorts of BXD mice. Using systems genetics, we also evaluated the role of other known pigmentation genes (PGs). Mapping studies indicate that Tyrp1 contributes to the phenotype at all ages, yet the TID maps to Gpnmb only in the oldest cohort. Composite interval mapping reveals secondary loci viz. Oca2, Myo5a, Prkcz, and Zbtb20 that modulate the phenotype in the age groups up to 10–13 months. The contributions of Tyrp1 and Gpnmb were highly significant in all age cohorts. Moreover, in young mice, all six gene candidates had substantial interactions in our model. Our model accounted for 71–88% of the explained variance of the TID phenotype across the age bins. These results demonstrate that along with Tyrp1 and Gpnmb, Oca2, Myo5a, Prkcz, and Zbtb20 modulate the TID in an age‐dependent manner.