bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionic strength- and pH-dependence of calcium binding by terrestrial humic acids
Authors: Christl Iso
Published: February 2012

Environmental contextIn terrestrial environments, humic substances act as major sorbents for calcium, which is an essential nutrient for organisms. This study shows that calcium binding by terrestrial humic acids is strongly dependent on pH and ionic strength. The results indicate that calcium binding by humic acids is primarily controlled by electrostatic forces and specific binding to carboxylic groups.
AbstractCalcium binding by two terrestrial humic acids was investigated at 25 °C as a function of pH, ionic strength and Ca2+ activity with calcium titration experiments. A Ca2+-selective electrode was used for Ca2+ measurements to cover a wide range of Ca2+ activities (10–8.5–10–2.5). Experimental data were quantitatively described with the NICA–Donnan model accounting for electrostatic and specific calcium binding. The results showed that calcium binding as a function of Ca2+ activity was strongly affected by variations of pH and ionic strength indicating that electrostatic binding is an important mechanism for calcium binding by humic acids. Data modelling providing a good description of experimental data for both humic acids suggested that electrostatic binding was the dominant calcium binding mechanisms at high Ca2+ activities often observed in terrestrial environments. Specific calcium binding being quantitatively predominant only at low Ca2+ activities was exclusively attributed to binding sites exhibiting a weak affinity for protons considered to represent mainly carboxylic groups. Since the negative charge of the humic acids being prerequisite for electrostatic calcium binding was found to be mainly due to deprotonation of carboxylic groups except under alkaline conditions, carboxylic groups were identified to primarily control calcium binding of humic acids.
A core erythroid transcriptional network is repressed by a master regulator of myelo-lymphoid differentiation
Authors: Wontakal Sandeep N. , Guo Xingyi , Smith Cameron , MacCarthy Thomas , Bresnick Emery H. , Bergman Aviv , Snyder Michael P. , Weissman Sherman M. , Zheng Deyou , Skoultchi Arthur I.
Published: February 2012

Two mechanisms that play important roles in cell fate decisions are control of a “core transcriptional network” and repression of alternative transcriptional programs by antagonizing transcription factors. Whether these two mechanisms operate together is not known. Here we report that GATA-1, SCL, and Klf1 form an erythroid core transcriptional network by co-occupying >300 genes. Importantly, we find that PU.1, a negative regulator of terminal erythroid differentiation, is a highly integrated component of this network. GATA-1, SCL, and Klf1 act to promote, whereas PU.1 represses expression of many of the core network genes. PU.1 also represses the genes encoding GATA-1, SCL, Klf1, and important GATA-1 cofactors. Conversely, in addition to repressing PU.1 expression, GATA-1 also binds to and represses >100 PU.1 myelo-lymphoid gene targets in erythroid progenitors. Mathematical modeling further supports that this dual mechanism of repressing both the opposing upstream activator and its downstream targets provides a synergistic, robust mechanism for lineage specification. Taken together, these results amalgamate two key developmental principles, namely, regulation of a core transcriptional network and repression of an alternative transcriptional program, thereby enhancing our understanding of the mechanisms that establish cellular identity.
Corrigendum: Analysis of damping rate measurements of toroidal Alfvén eigenmodes as a function of n: part II
Authors: Panis T. , Fasoli A. , Testa D. , Contributors JET-EFDA
Published: February 2012

The authors would like to correct an error in the title of their paper (2012Nucl. Fusion52023014). The full title of the work should read: ‘Analysis of damping rate measurements of toroidal Alfvén eigenmodes on JET as a function ofn: part II’.
Molecular basis for phosphospecific recognition of histone H3 tails by Survivin paralogues at inner centromeres
Authors: Niedzialkowska Ewa , Wang Fangwei , Porebski Przemyslaw J. , Minor Wladek , Higgins Jonathan M. G. , Stukenberg P. Todd
Published: February 2012

Survivin, a subunit of the chromosome passenger complex (CPC), binds the N-terminal tail of histone H3, which is phosphorylated on T3 by Haspin kinase, and localizes the complex to the inner centromeres. We used x-ray crystallography to determine the residues of Survivin that are important in binding phosphomodified histone H3. Mutation of amino acids that interact with the histone N-terminus lowered in vitro tail binding affinity and reduced CPC recruitment to the inner centromere in cells, validating our solved structures. Phylogenetic analysis shows that nonmammalian vertebrates have two Survivin paralogues, which we name class A and B. A distinguishing feature of these paralogues is an H-to-R change in an amino acid that interacts with the histone T3 phosphate. The binding to histone tails of the human class A paralogue, which has a histidine at this position, is sensitive to changes around physiological pH, whereas Xenopus Survivin class B is less so. Our data demonstrate that Survivin paralogues have different characteristics of phosphospecific binding to threonine-3 of histone H3, providing new insight into the biology of the inner centromere.
Phosphorylation of threonine 1736 in the C-terminal tail of integrin β4 contributes to hemidesmosome disassembly
Authors: Frijns Evelyne , Kuikman Ingrid , Litjens Sandy , Raspe Marcel , Jalink Kees , Ports Michael , Wilhelmsen Kevin , Sonnenberg Arnoud
Published: February 2012

During wound healing, hemidesmome disassembly enables keratinocyte migration and proliferation. Hemidesmosome dynamics are altered downstream of epidermal growth factor (EGF) receptor activation, following the phosphorylation of integrin β4 residues S1356 and S1364, which reduces the interaction with plectin; however, this event is insufficient to drive complete hemidesmome disassembly. In the studies reported here, we used a fluorescence resonance energy transfer–based assay to demonstrate that the connecting segment and carboxy-terminal tail of the β4 cytoplasmic domain interact, which facilitates the formation of a binding platform for plectin. In addition, analysis of a β4 mutant containing a phosphomimicking aspartic acid residue at T1736 in the C-tail suggests that phosphorylation of this residue regulates the interaction with the plectin plakin domain. The aspartic acid mutation of β4 T1736 impaired hemidesmosome formation in junctional epidermolysis associated with pyloric atresia/β4 keratinocytes. Furthermore, we show that T1736 is phosphorylated downstream of protein kinase C and EGF receptor activation and is a substrate for protein kinase D1 in vitro and in cells, which requires its translocation to the plasma membrane and subsequent activation. In conclusion, we identify T1736 as a novel phosphorylation site that contributes to the regulation of hemidesmome disassembly, a dynamically regulated process involving the concerted phosphorylation of multiple β4 residues.
The Effects of Farm Commodity and Retail Food Policies on Obesity and Economic Welfare in the United States
Authors: Okrent Abigail M. , Alston Julian M.
Published: February 2012

Many commentators claim that farm subsidies have contributed significantly to the “obesity epidemic” by making fattening foods relatively cheap and abundant and, symmetrically, that taxing “unhealthy” commodities or subsidizing “healthy” commodities would contribute to reducing obesity rates. In this article we use an equilibrium displacement model to estimate and compare the economic welfare effects from a range of hypothetical farm commodity and retail food policies as alternative mechanisms for encouraging consumption of healthy food or discouraging consumption of unhealthy food, or both. We find that, compared with retail taxes on fat, sugar, or all food, or subsidies on fruits and vegetables at the farm or retail levels, a tax on calories would be the most efficient obesity policy. A tax on calories would have the lowest deadweight loss per pound of fat reduction in average adult weight, and would yield a net social gain once the impact on public health care expenditures is considered.
A brain-derived metric for preferred kinetic stimuli
Authors: Zeki Semir , Stutters Jonathan
Published: February 2012

We here address the question of whether there is any correlation between subjective preference for simple configurations within a specific visual domain such as motion and strength of activity in visual areas in which that domain is emphasized. We prepared several distinctive patterns of dots in motion with various characteristics and asked humans to rate them according to their preference, before and while scanning the activity in their brains with functional magnetic resonance imaging. For simplicity, we restricted ourselves to motion in the fronto-parallel plane. Moving patterns produced activity in areas V1, V2, the V3 complex (V3, V3A, V3B) and V5, but only in areas V5, V3A/B and parietal cortex did the preferred kinetic patterns produce stronger activity when compared with the non-preferred ones. In addition, preferred patterns produced activity within field A1 of medial orbito-frontal cortex (mOFC), which is not otherwise activated by kinetic stimuli. Hence, for these areas, stronger neural activity correlated with subjective preference. We conclude that configurations of kinetic stimuli that are subjectively preferred correlate with stronger activity within early visual areas and within mOFC. This opens up the possibility of more detailed studies to relate subjective preferences to strength of activity in early visual areas and to relate activity in them to areas whose activity correlates with the subjective experience of beauty.
Nine closely related tetrahydro-1,4-epoxy-1-benzazepines carrying pendant heterocyclic substituents: hydrogen-bonded supramolecular assembly in zero, one and two dimensions
Authors: Blanco Maria C. , Palma Alirio , Cobo Justo , Glidewell Christopher
Published: February 2012

The structures are reported of nine closely related tetrahydro-1,4-epoxy-1-benzazepines carrying pendant heterocyclic substituents, namely: 2-exo-(5-nitrofuran-2-yl)-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C14H12N2O4, (I), 7-fluoro-2-exo-(1-methyl-1H-pyrrol-2-yl)-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C15H15FN2O, (II), 7-fluoro-2-exo-(5-methylfuran-2-yl)-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C15H14FNO2, (III), 7-fluoro-2-exo-(3-methylthiophen-2-yl)-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C15H14FNOS, (IV), 7-fluoro-2-exo-(5-methylthiophen-2-yl)-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C15H14FNOS, (V), 7-chloro-2-exo-(5-methylfuran-2-yl)-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C15H14ClNO2, (VI), 2-exo-(5-methylfuran-2-yl)-7-trifluoromethoxy-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C16H14F3NO3, (VII), 2-exo-(3-methylthiophen-2-yl)-7-trifluoromethoxy-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C16H14F3NO2S, (VIII), and 2-exo-(5-nitrofuran-2-yl)-7-trifluoromethoxy-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C15H11F3N2O5, (IX). All nine compounds crystallize in centrosymmetric space groups as racemic mixtures with configuration (2RS,4SR). There are no direction-specific interactions between the molecules in (V). The molecules in (III), (IV), (VI) and (VII) are linked into simple chains, by means of a single C—H...O hydrogen bond in each of (III), (VI) and (VII), and by means of a single C—H...π(arene) hydrogen bond in (IV), while the molecules in (VIII) are linked into a chain of rings. In each of (I) and (II), a combination of one C—H...O hydrogen bond and one C—H...π(arene) hydrogen bond links the molecules into sheets, albeit of completely different construction in the two compounds. In (IX), the sheet structure is built from a combination of four independent C—H...O hydrogen bonds and one C—H...π(arene) hydrogen bond. Comparisons are made with some related compounds.
1-[(1-Ethoxypropylidene)amino]-2-ethyl-4-(4-hydroxybenzyl)imidazol-5(4H)-one
Authors: Ejsmont Krzysztof , Kudelko Agnieszka , Zieliński Wojciech
Published: February 2012

The racemic title compound, C17H23N3O3, isolated from the reaction of L-(−)-tyrosine hydrazide with triethyl orthopropionate in the presence of a catalytic quantity ofp-toluenesulfonic acid (p-TsOH), crystallizes withZ′ = 1 in a centrosymmetric monoclinic unit cell. The molecule contains two planar fragments,viz.the benzene and imidazole rings, linked by two C—C single bonds. The dihedral angle between the two planes is 59.54 (5)° and the molecule adopts a synclinal conformation. The HOMA (harmonic oscillator model of aromaticity) index, calculated for the benzene ring, demonstrates no substantial interaction between the two π-electron delocalization regions in the molecule. In the crystal structure, there is an O—H...N hydrogen bond that links the molecules along thecaxis.
Gymnotus capanema, a new species of electric knife fish (Gymnotiformes, Gymnotidae) from eastern Amazonia, with comments on an unusual karyotype
Authors: Milhomem S. S. R. , Crampton W. G. R. , Pieczarka J. C. , Shetka G. H. , Silva D. S. , Nagamachi C. Y.
Published: February 2012

Gymnotus capanema n. sp. is described on the basis of cytogenetic, morphometric, meristic and osteological data from nine specimens (one male and eight females) from the municipality of Capanema, Pará, in the eastern Amazon of Brazil. Later, three additional specimens were found in museums and regarded as nontypes (not cytogenetically analysed). Gymnotus capanema, which occurs in sympatry with Gymnotus cf. carapo cytotype 2n = 42 (30m/sm + 12st/a) exhibits a novel karyotype for the genus, with 2n = 34 (20m/sm + 14st/a). Gymnotus capanema can be unambiguously diagnosed from all congeners on the basis of a combination of characters from external anatomy, pigmentation and osteology. The constitutive heterochromatin, rich in adenine‐thymine (A‐T) base pairs [4′,6 diamidino‐2‐phenylindole dihydrochloride (DAPI) positive], occurs in the centromeric region of all of the chromosomes, and in the pericentromeric and the entire short arm of some chromosomes. The nucleolar organizing region (NOR), stained by silver nitrate, chromomycin A3 (CMA3) and 18S ribosomal (r)DNA fluorescence in situ hybridization (FISH), occurs in the short arm of pair 15. FISH, with telomeric probes did not show interstitial telomeric sequences (ITS), despite the reduced 2n in comparison to the karyotypes of other species of Gymnotus. The karyotype of G. capanema, with a reduced 2n, is strikingly different from all other previously studied congeners.
Variation in gene expression along a salinity gradient in wild populations of the euryhaline black‐chinned tilapia Sarotherodon melanotheron
Authors: Tine M. , Guinand B. , Durand J.‐D.
Published: February 2012

This study evaluated variation in expression of 11 genes within and among six wild populations of the black‐chinned tilapia Sarotherodon melanotheron distributed along a salinity gradient from 0 to 100. Previous laboratory studies had shown that expression of these genes was sensitive to water salinity; the current study confirmed that a number of them also varied in expression in wild populations along the salinity gradient. Principal component analysis (PCA) first distinguished two, not mutually exclusive, sets of genes: trade‐off genes that were highly expressed at one or other extreme of the salinity gradient and stress genes that were up‐regulated at the two salinity extremes (i.e. a U‐shaped expression pattern). The PCA clearly partitioned the populations into three groups based on their gene expression patterns and their position along the salinity gradient: a freshwater (GL; 0) population, four brackish and seawater (GB, HB, SM, SF; ranging from 20 to 50) populations and a hypersaline (SK, 100) population. Individual variation in gene expression was significantly greater within the populations at the extreme compared to intermediate salinities. These results reveal phenotypically plastic regulation of gene expression in S. melanotheron, and greater osmoregulatory and plasticity costs at extreme salinities, where fitness‐related traits are known to be altered.
Early life migration patterns of Baltic Sea pike Esox lucius
Authors: Rohtla M. , Vetemaa M. , Urtson K. , Soesoo A.
Published: February 2012

This study investigated the movement patterns of Baltic Sea pike Esox lucius in Matsalu Bay, Estonia, using otolith microchemistry. Migration patterns of E. lucius were remarkably diverse, but distinct groups were evident. Of the E. lucius analysed (n = 28), 82% hatched in fresh water and 74% of them left this biotope during the first growth season.
Audit Expectation‐Performance Gap Revisited: Evidence from New Zealand and the United Kingdom. Part 2: Changes in the Gap in New Zealand 1989–2008 and in the United Kingdom 1999–2008
Authors: Porter Brenda , hÓgartaigh Ciaran Ó , Baskerville Rachel
Published: February 2012

Investigation of changes in the audit expectation‐performance gap in New Zealand (NZ) and the United Kingdom (UK) revealed that, between 1989 and 1999, in both countries the reasonableness gap widened as developments in auditing's external environment stimulated an increase in society's unreasonable expectations of auditors but the deficient performance gap narrowed as monitoring of auditors' performance resulted in societal perception of improved performance. Between 1999 and 2008, in the UK, widespread discussion of the environmental developments and related audit issues, along with more stringent monitoring of auditors' performance, resulted in a narrowing of the reasonableness and deficient performance gaps. In NZ, lacking these factors, these gaps widened. Additionally, changes to auditing standards resulted in some ‘reasonably expected’ responsibilities becoming actual responsibilities of auditors and, in both countries, the deficient standards gap narrowed. The research findings illuminate the means by which the audit expectation‐performance gap might be narrowed.
Immunosuppressive activity of CD14+ HLA‐DR− cells in squamous cell carcinoma of the head and neck
Authors: Chikamatsu Kazuaki , Sakakura Koichi , Toyoda Minoru , Takahashi Katsumasa , Yamamoto Takanori , Masuyama Keisuke
Published: February 2012

Myeloid‐derived suppressor cells (MDSC) represent a heterogeneous population and have the potential to suppress immune responses via diverse mechanisms. In recent studies, a new subset of MDSC was identified by the markers CD14+ and HLA‐DR− in the peripheral blood from cancer patients. In this study, we investigated the proportions and characteristics of CD14+ HLA‐DR− cells in patients with squamous cell carcinoma of the head and neck (SCCHN). As expected, the percentage of CD14+ HLA‐DR− cells was significantly elevated in patients relative to healthy donors and the sorted CD14+ HLA‐DR− cells were able to suppress effectively both the proliferation and IFN‐γ production of anti‐CD3/anti‐CD28 stimulated T cells, suggesting that CD14+ HLA‐DR− cells in patients with SCCHN contribute to the immune suppressive status. Furthermore, CD14+ HLA‐DR− cells revealed a higher level of CD86 and PD‐L1 expression and transforming growth factor (TGF)‐β production than CD14+ HLA‐DR+ cells. Addition of anti‐CD86 mAb, anti‐PD‐L1 mAb and anti‐TGF‐β mAb partially restored T‐cell proliferation and IFN‐γ production, respectively, indicating that the suppressive effects of CD14+ HLA‐DR− cells appear to be mediated by various molecules, including coinhibitory molecules and cytokines. Our data suggest that CD14+ HLA‐DR− cells act as potent immunosuppressive cells and particularly contribute to tumor escape from the host immune system in patients with SCCHN. (Cancer Sci 2012; 103: 976–983)
Androgen deprivation causes truncation of the C‐terminal region of androgen receptor in human prostate cancer LNCaP cells
Authors: Harada Naoki , Inoue Kaoru , Yamaji Ryoichi , Nakano Yoshihisa , Inui Hiroshi
Published: February 2012

The androgen receptor (AR) acts as a ligand‐dependent transcription factor, whereas mutant AR lacking the C‐terminal ligand‐binding domain functions in a ligand‐independent manner. In the present study we report that the C‐terminal truncated AR, which we named AR‐NH1 (the N‐terminal fragment of AR cleaved in the neighborhood of helix 1 of the ligand‐binding domain), is produced in LNCaP prostatic carcinoma cells. The AR‐NH1 of ~90 kDa was observed in an androgen‐independent LNCaP subline and was further accumulated by the proteasome inhibitor MG132. MG132 treatment caused the accumulation of AR‐NH1 even in parent LNCaP cells. AR‐NH1 was produced in the absence of ligand or in the presence of the AR antagonist bicalutamide, whereas AR agonists suppressed its production. AR‐NH1 was detected with different AR antibodies recognizing amino acid residues 1–20 and 300–316 and was also generated from exogenous AR. Both siRNA‐mediated AR knockdown and treatment with a serine protease inhibitor (4‐(2‐aminoethyl)‐benzenesulfonyl fluoride) reduced AR‐NH1 levels. According to the predicted cleavage site (between amino acid residues 660–685) and its nuclear localization, it is assumed that AR‐NH1 functions as a constitutively active transcription factor. These data suggest that AR‐NH1 is produced under hormone therapy and contributes to the development of castration‐resistant prostate cancer due to its ligand‐independent transcriptional activity. (Cancer Sci 2012; 103: 1022–1027)
Aggressive natural killer cell leukemia: Therapeutic potential of l‐asparaginase and allogeneic hematopoietic stem cell transplantation
Authors: Ishida Fumihiro , Ko Young Hyeh , Kim Won Seog , Suzumiya Junji , Isobe Yasushi , Oshimi Kazuo , Nakamura Shigeo , Suzuki Ritsuro
Published: February 2012

We conducted a retrospective Japan–Korea multicenter study to better elucidate the clinicopathologic features and therapeutic modalities for aggressive natural killer cell leukemia (ANKL). A total of 34 patients were analyzed. The median age of the patients was 40 years. Among the patients in the study, four had a history of Epstein–Barr virus‐related disorders. Three types of ANKL cells were categorized according to their morphological features. Leukemic cells were below 20% in both peripheral blood and bone marrow of 11 patients. The clinical characteristics and prognoses of these 11 patients did not differ significantly from those of the others. As an initial therapy, l‐asparaginase chemotherapy resulted in a better response. A total of six patients received allogeneic hematopoietic stem cell transplantation (HSCT) and two received autologous HSCT, with all in non‐complete remission (CR). After HSCT, four with allogeneic and one with autologous HSCT reached CR. Median survival of all patients was 51 days. Median survival for the patients with and without HSCT were 266 and 36 days, respectively. A total of two patients with allogeneic HSCT were alive and in CR. All patients without HSCT died of ANKL. The use of l‐asparaginase was indicated as a factor for longer survival (HR 0.33, 95% confidence interval; 0.13–0.83, P = 0.02). Early diagnosis of ANKL, l‐asparaginase‐based chemotherapy and allogeneic HSCT might lead to improved patient outcomes. (Cancer Sci 2012; 103: 1079–1083)
Predictors of severe outcomes associated with Clostridium difficile infection in patients with inflammatory bowel disease
Authors: Ananthakrishnan A. N. , Guzman‐Perez R. , Gainer V. , Cai T. , Churchill S. , Kohane I. , Plenge R. M. , Murphy S.
Published: February 2012

Background

The increasing incidence of Clostridium difficile (C. difficile) infection (CDI) among patients with inflammatory bowel disease is well recognised. However, most studies have focused on demonstrating that CDI is associated with adverse outcomes in IBD patients. Few have attempted to identify predictors of severe outcomes associated with CDI among IBD patients.

Aim

To identify clinical and laboratory factors that predict severe outcomes associated with CDI in IBD patients.

Methods

From a multi‐institution EMR database, we identified all hospitalised patients with at least one diagnosis code for C. difficile from among those with a diagnosis of Crohn's disease or ulcerative colitis. Our primary outcome was time to total colectomy or death with follow‐up censored at 180 days after CDI. Cox proportional hazards models were used to identify predictors of the primary outcome from among demographic, disease‐related, laboratory and medication variables.

Results

A total of 294 patients with CDI‐IBD were included in our study. Of these, 58 patients (20%) met our primary outcome (45 deaths, 13 colectomy) at a median of 31 days. On multivariate analysis, serum albumin <3 g/dL (HR 5.75, 95% CI 1.34–24.56), haemoglobin below 9 g/dL (HR 5.29, 95% CI 1.58–17.69) and creatinine above 1.5 mg/dL (HR 1.98, 95% CI 1.04–3.79) were independent predictors of our primary outcome. Examining laboratory parameters as continuous variables or shortening our primary outcome to include events within 90 days yielded similar results.

Conclusion

Serum albumin below 3 g/dL, haemoglobin below 9 g/dL and serum creatinine above 1.5 mg/dL were independent predictors of severe outcomes in hospitalised IBD patients with Clostridium difficile infection.
An agenda for UK clinical pharmacology: Developing and delivering clinical pharmacology in the UK National Health Service
Authors: Routledge Philip A.
Published: February 2012

Clinical pharmacologists are active in the delivery of general and specialist medical services across the UK. They also make major contributions, both locally and nationally, to medicines management and appraisal in the National Health Service. Most are also heavily involved in the organization and delivery of teaching and training of a range of healthcare professionals, both undergraduates and postgraduates. In the past, these contributions may not have been fully recognized, perhaps in part because the discipline is small. However, the British Pharmacological Society, particularly through its Clinical Section, is committed to initiatives to ensure that all clinical pharmacologists (whatever their background, training or subsequent working environment) can work together to improve patient care, nationally and internationally. Effective engagement with universities, the National Health Service and pharmaceutical companies will be vital if these initiatives are to have sustained benefits and improve health outcomes for patients.
An agenda for UK clinical pharmacology: How should teaching of undergraduates in clinical pharmacology and therapeutics be delivered and assessed?
Authors: Maxwell Simon R. J.
Published: February 2012

Clinical pharmacology and therapeutics is the academic discipline that informs rational prescribing of medicines. There is accumulating evidence that a significant minority of prescriptions in the UK National Health Service contain errors. This comes at a time when the approach to and success of undergraduate education in this area has been called into question. Various stakeholders are now in agreement that this challenging area of undergraduate education needs to be strengthened. The principles that should form the basis of future educational strategy include greater visibility of clinical pharmacology and therapeutics in the curriculum, clear learning outcomes that are consistent with national guidance, strong and enthusiastic leadership, a student formulary, opportunities to practice prescribing, a robust assessment of prescribing competencies and external quality control. Important new developments in the UK are Prescribe, a repository of e‐learning materials to support education in clinical pharmacology and prescribing, and the Prescribing Skills Assessment, a national online assessment designed to allow medical students to demonstrate that they have achieved the core competencies required to begin postgraduate training.
Finding a VOICE for UK clinical pharmacology
Authors: Aronson Jeffrey K.
Published: February 2012

At a James Black Conference held in Oxford on 20–22 June 2011, a group of senior clinical pharmacologists and their junior colleagues, other medical specialists, and pharmacists discussed an agenda for UK clinical pharmacology for the next 5 years, addressing the following broad questions. How should UK clinical pharmacology be further developed and delivered as a discipline in universities, the NHS, pharmaceutical companies, and regulatory authorities? How should teaching and training in UK clinical pharmacology and therapeutics be delivered and assessed? What topics should be priorities for research in UK academic clinical pharmacology? How should clinical pharmacology contribute to UK drugs policy? How should pharmacology and clinical pharmacology be further integrated, to the benefit of both? Numerous recommendations emerged, under the collective acronym VOICE, standing for Visibility, Outreach, Integration, Coverage and Emissaries.

Visibility
The visibility of the discipline needs to be increased. This could be done, for example, by increased activities in acute general medicine/toxicology, through activities of Medicines and Therapeutics Committees, participation in grand rounds, teaching and training, and monitoring therapeutic interventions, and by offering bolt‐on training for other specialists (for example, short courses, MSc courses, and training programmes).

Outreach
Methods of increasing outreach include roadshows in schools/medical schools, national special study modules, public education, press coverage, and social marketing.

Integration
Closer collaborations with pharmacologists, clinical pharmacists, other prescribers, and pharmaceutical companies (e.g. through joint training programmes) are desirable.

Coverage
Attention to neglected areas, such as general practice, paediatrics, obstetrics, geriatrics, anaesthetics, cancer, and immunology.

Emissaries
Trainees to spread the word.
An agenda for UK clinical pharmacology: Research priorities in biomarkers and surrogate end‐points
Authors: Aronson Jeffrey K.
Published: February 2012

Ideal tests of the effects of therapeutic interventions measure the desired outcomes; however, the desired outcomes are not always easily measured or may be long‐term objectives. Biomarkers and surrogate end‐points are often cheaper and easier to measure and can be measured over a shorter time span. They can be used in screening, diagnosing, staging, and monitoring diseases, in monitoring responses to interventions, and in various aspects of drug discovery and development. They can be extrinsic to the body or intrinsic, and can relate to any point in the pharmacological chain, at the molecular, cellular, tissue, or organ level. Problems arise when the relation between the pathophysiology of the disease and the mechanism of action of the intervention is not properly understood; when adverse effects obviate therapeutic effects; when confounding factors, such as other drugs, alter the surrogate independently of the final end‐point; when a biomarker persists after resolution of the disease; and when the concentration–effect curves for the effects of an intervention on the primary outcome and the surrogate are different. Use of biomarkers may also be hindered by poor reproducibility of measurement techniques. Challenges for clinical pharmacologists are to devise biomarker tests that are reliable, reproducible, sensitive, and specific, and surrogate end‐points that are associated with the clinical outcomes of concern and useful. A robust taxonomy is needed of the relations that link the pathophysiology of disease, the mechanisms of action of interventions and their adverse effects, the desired clinical outcomes, and the surrogate end‐points that predict them.
An agenda for UK clinical pharmacology: Adverse drug reactions
Authors: Loke Yoon K.
Published: February 2012

Our ability to understand fully the characteristics of clinically important adverse drug reactions is hindered by a lack of emphasis on biological mechanisms, patient susceptibility factors and long‐term outcomes. Assessment of drug safety needs to move beyond industry and regulatory perspectives, towards a greater focus on evidence‐based preventive and management strategies that will allow patients and physicians to deal with adverse drug reactions at the bedside. This would ideally involve close collaboration between clinical pharmacologists and pharmacoepidemiologists skilled at interrogating the increasingly sophisticated electronic healthcare databases. In light of the myriad safety scares that are constantly emerging, patients and physicians would be best served by a centrally funded independent network of rapid‐response drug safety researchers who can use techniques of teleoanalysis to describe fully the magnitude of risk, the potential biological mechanisms and patients' susceptibility factors.
An agenda for UK clinical pharmacology: The potential of the internet
Authors: Coleman Jamie J. , McDowell Sarah E.
Published: February 2012

The internet and the World Wide Web have changed the ways that we function. As technologies grow and adapt, there is a huge potential for the internet to affect drug research and development, as well as many other aspects of clinical pharmacology. We review some of the areas of interest to date and discuss some of the potential areas in which internet‐based technology can be exploited.

Information retrieval from the web by health‐care professionals is common, and bringing evidence‐based medicine to the bedside affects the care of patients.

As a primary research tool the web can provide a vast array of information in generating new ideas or exploring previous research findings. This has facilitated systematic reviewing, for example. The content of the web has become a subject of research in its own right.

The web is also widely used as a research facilitator, including enhancement of communication between collaborators, provision of online research tools (such as questionnaires, management of large scale multicentre trials, registration of clinical trials) and distribution of information.

Problems include information overload, ignorance of early data that are not indexed in databases, difficulties in keeping web sites up to date and assessing the validity of information retrieved. Some web‐based activities are viewed with suspicion, including analysis by pharmaceutical companies of drug information to facilitate direct‐to‐consumer advertising of novel pharmaceuticals.

Use of these technologies will continue to expand in often unexpected ways. Clinical pharmacologists must embrace internet technology and include it as a key priority in their research agenda.
An agenda for UK clinical pharmacology: Pharmacovigilance
Authors: Edwards I. Ralph
Published: February 2012

Adverse drug reactions are the fifth most frequent cause of deaths in developed countries, effectively a global epidemic. However, progress in ameliorating the problem has been slow. Pharmacovigilance currently operates without clear objectives in relation to individual decisions, with no protocol (although risk management plans are a great step forward), with obscure materials and methods used for making decisions, with very limited reasoning and discussion, and little or no follow up and audit of the results. Problems include under‐reporting, poor quality reports, underuse of the latest communications technology and suboptimal individual feedback to reporters. Assessment of causality is poor, impeding decision‐making. After signal detection, more active measures to assess the risk to public health are needed. Other essential factors include precision about the ways in which data are prepared and transformed into databases, the recognition of secondary effects, which may be more obvious than the primary effect, but not so easy to link causally, and cognisance of all kinds of interactions. Areas that should be developed include pharmacoepidemiology, knowledge finding (through data mining), and communication and systems technology. The general way forward seems clear: a rigorous way of documenting all the steps, from getting reports of harms into regulatory databases to assessing their effects on public health, is essential and should be publicly reviewed for weaknesses. In turn, matters would be much improved by input on benefit/harm perceptions from patient groups, influencing decisions about what should be the true targets for regulatory and pharmacovigilance activities, avoiding second guessing by regulators.
Comparing empirical models for sediment and phosphorus transfer from soils to water at field and catchment scale under data uncertainty
Authors: Krueger T. , Quinton J. N. , Freer J. , Macleod C. J. A. , Bilotta G. S. , Brazier R. E. , Hawkins J. M. B. , Haygarth P. M.
Published: February 2012

Soils are important sources of sediment and phosphorus in rural catchments, necessitating the development of mathematical models for impact assessment. In this paper, multiple empirical models are tested on an event basis at four nested locations in an intensively managed grassland headwater catchment while accounting for parameter and data uncertainties using extended Generalized Likelihood Uncertainty Estimation (GLUE). The study provides the first template of model comparison under data uncertainty in soil erosion and phosphorus transfer modelling as well as hypotheses of soil and water processes in the study catchment. A fodder field, yielding large sediment and phosphorus concentrations in runoff, is characterized by inter‐event variation in sediment‐discharge relationship, mild intra‐event hysteretic behaviour and seemingly random erosion incidents. Sediment‐discharge variation is partly formalized by parameter variation as a function of antecedent soil moisture, indicative of a gradual shift from transport‐ to source‐limited behaviour, decreasing soil erodibility and/or decreasing initial flow erosivity and transport capacity with increasing antecedent wetness. The catchment outlet appears to be source‐limited while converging flows with different sediment concentrations, variable erosion processes and/or sporadic entrainment of near‐ or in‐stream sediments gain importance. Phosphorus dynamics are strongly linked to those of sediment. Non‐linearities can be explained by preferential transfer of phosphorus‐rich organic matter at small flows while there is no significant evidence of preferential transfer of phosphorus‐rich mineral fines. Iterating between collecting data, constraining uncertainties and rejecting and improving models is suggested as a consistent framework for understanding soil erosion and phosphorus movement.
Obtaining consensus about patient‐centred professionalism in community nursing: nominal group work activity with professionals and the public
Authors: Hutchings Hayley , Rapport Frances , Wright Sarah , Doel Marcus , Jones Aled
Published: February 2012

hutchings h., rapport f., wright s., doel m. & jones a. (2012) Obtaining consensus about patient‐centred professionalism in community nursing: nominal group work activity with professionals and the public. Journal of Advanced Nursing68(11), 2429–2442.

Aim.  To report on the development of a ranked thematic list encompassing the positive and challenging exemplars of patient‐centred professionalism in community nursing.

Background.  There has been little research exploring what ‘patient‐centred professionalism’ means to those working within the healthcare settings. Consensus methods, such as those developed through Nominal Group Work, can help establish the extent of agreement on a particular issue whilst overcoming some of the problems associated with group decision‐making.

Design.  Mixed methods studying through consultation workshops.

Method.  The study took place in South‐west Wales, UK between October 2009–September 2010. Thirty‐four participants consisting of community nurses (9), newly qualifying nurses (13), nursing stakeholders (6) and members of the public (6) took part in the study. An adapted Nominal Group Work approach was used in five individual consultation workshops: two with community nurses, one with newly qualifying nurses, one with stakeholders and one with members of the public followed by a mixed‐group Forum event.

Results.  Each of the five workshops resulted in the production of approximately ten positive and ten challenging exemplars of patient‐centred professionalism. The thematization of these exemplars allowed the development of eight broad themes. The Forum event then provided a mechanism for ranking the importance of these themes. The patient, community nurse as a person and nursing ethos were ranked as the most important themes by study participants.

Conclusions.  The adapted Nominal Group Work approach was a useful method to allow the development of a ranked thematic list that illustrated the important positive and challenging exemplars of patient‐centred professionalism in community nursing.
Health, lifestyle, belief and knowledge differences between two ethnic groups with specific reference to tobacco, diet and physical activity
Authors: Anthony Denis , Baggott Rob , Tanner Judith , Jones Kathryn , Evans Hala , Perkins Gill , Palmer Hilary ,   on behalf of the Community Interventions for Health (CIH) collaboration
Published: February 2012

anthony d., baggott r., tanner j., jones k., evans h., perkins g. & palmer h. (2012) Health, lifestyle, belief and knowledge differences between two ethnic groups with specific reference to tobacco, diet and physical activity. Journal of Advanced Nursing68(11), 2496–2503.

Aims.  To compare physical activity levels, body mass index, habitual diet, tobacco use and prevalence of non‐communicable disease between the two ethnic groups and to identify predictors for differences between groups.

Background.  Tobacco use, poor diet and physical inactivity are major lifestyle risk factors for chronic cardiovascular diseases, certain cancers, diabetes and chronic lung diseases. There are higher risk and incidence of these diseases in some ethnic groups, for example Asians have higher incidence of diabetes.

Design.  Cross sectional survey.

Methods.  Cross sectional survey of Asians of Indian descent and white British adults conducted between October–December 2009. Main outcome variables were lifestyle behaviours and BMI. Self‐reported disease diagnosis was also collected. In a regression analysis, predictors of outcome variables were demographic variables and beliefs/attitudes/knowledge towards lifestyle behaviours.

Results/Findings.  Body mass index, tobacco use and non‐communicable disease (except diabetes) were lower in Indians. Indians reported lower physical activity levels and greater salt use than Whites. Tobacco use was higher in Whites, but knowledge, attitudes and beliefs were similar between Whites and Indians.

Conclusion.  Health risk behaviour and morbidity are different between the two ethnic groups. Gender, age, educational level, beliefs, attitudes and knowledge do not explain these differences. Health promotion that aims to improve knowledge will probably not work and innovative methods are needed to improve health in high risk groups.
Nutrition and prevalence of undernutrition assessed by different diagnostic criteria in nursing homes for elderly people
Authors: López‐Contreras M.‐J. , Torralba C. , Zamora S. , Pérez‐Llamas F.
Published: February 2012

How to cite this article: López‐Contreras M.‐J., Torralba C., Zamora S. & Pérez‐Llamas F. (2012) Nutrition and prevalence of undernutrition assesed by different diagnostic criteria in nursing homes for elderly people. J Hum Nutr Diet. 25, 239–246

Background:  Undernutrition is the state produced by the intake of insufficient energy, macronutrients or micronutrients. The present study aimed to assess the prevalence of undernutrition using 10 different diagnostic criteria described in the literature and to assess its association with energy intake in an institutionalised elderly population.

Methods:  The cross‐sectional study included 213 subjects, aged 65–96 years (135 women and 78 men), who lived in seven nursing homes in the province of Murcia, on the Mediterranean coast of Spain. Dietary intake and anthropometric and biochemical parameters were assessed, and 10 different diagnostic criteria, taken from studies of elderly subjects similar to our population, were applied.

Results:  The mean dietary intakes appeared to cover the recommended dietary intake for a Spanish elderly population. However, only 58.2% of the studied subjects consumed 100% of the recommended dietary intake and 15.5% of the subjects had an energy intake below 80% of the recommended dietary intake. Depending on the criteria used for the diagnosis, the proportion of patients with undernutrition varied between 2% and 57%. When the relationship between undernourishment, as defined by the different methods and intake deficiency, was assessed, a statistically significant relationship was only found for five of the 10 diagnostic criteria assessed.

Conclusions:  Research needs to focus on the development and evaluation of specific nutritional assessment tools for application to older people aiming to improve the detection of those suffering (or who are at risk of suffering) undernutrition.
Clustering and stability of functional lower gastrointestinal symptom after enteric infection
Authors: Thabane M. , Simunovic M. , Akhtar‐Danesh N. , Garg A. X. , Clark W. F. , Marshall J. K.
Published: February 2012

Background  Current diagnostic criteria for functional gut disorder are based on symptom clusters observed after sporadic onset. It remains unclear whether symptoms group similarly in functional disorders of postinfectious etiology. We utilized observational data from the Walkerton Health Study (WHS) to: (i) determine groupings of functional gastrointestinal symptoms among patients exposed to acute gastroenteritis (GE), and (ii) assess the stability of these symptoms grouping over time.

Methods  WHS participants 16 years of age and older at the time of the outbreak were included, if they had completed a modified Talley’s Bowel Disease Questionnaire (BDQ) and responded ‘yes’ to a screening question as to whether they had experienced abdominal pain in the last 2 weeks. Exploratory factor analysis (EFA) using tetrachoric correlations was undertaken to identify symptom constructs. Hierarchical cluster analysis using the k‐means method was used to create cluster groupings of patients based on these factors. Confirmatory factors analysis using responses to BDQ questionnaire administered at 4, 6, and 8 years after the outbreak was performed to assess stability of symptom domains over time.

Key Results  A total of 773 participants were eligible for inclusion [62.2% female, mean age 43.1 years (SD = 16.9)]. Eighty‐four percent were exposed to acute GE during the outbreak. Two symptom groupings of abdominal pain with either diarrhea or constipation together explained 85.7% of the total variance. Cluster analysis identified four patients groupings based on these factors. These clusters could be qualitatively described as diarrhea‐ and constipation‐predominant, mixed bowel pattern, and no predominance of bowel movements abnormalities. Results of the confirmatory factor analysis validating symptom domains identified in Year 1 showed that the baseline model was acceptable at 4 and 6 years after the outbreak and approached acceptability at 8 years. Values of root mean square error of approximation were 0.071 (90% CI: 0.053, 0.089) at 4 and 0.071 (90% CI: 0.049, 0.092) at 6 years and 0.089 (90% CI: 0.065, 0.114) at 8 years.

Conclusions & Inferences  The majority of subjects with postinfectious functional bowel disorders belong to groups with symptoms of abdominal pain and either diarrhea or constipation. These symptom groupings were stable across time.