Alexander des Grossen feldzüge in Turkestan; kommentar zu den geschichtswerken des Flavius Arrianus und Q. Curtius Rufus auf grund vieljähriger reisen im russischen Turkestan und den angrenzenden ländern.

Mode of access: Internet.

The apology of an officer, for withdrawing from the profession of arms : contained in a letter addressed to the King : and a series of letters to a friend on the causes and evils of war, its unlawfulness, &c.

"The Series of letters was published in three parts, and at different times. The 'Letter to the King' was published some time before them."--Preface p. ix.

Alexanders fest, oder Die Gewalt der Musik. Eine grosse Cantate aus dem Englischen des Dryden übersetzt von C. W. Ramler. Mit neuer Bearbeitung von W. A. Mozart.

Mode of access: Internet.

Life and letters of Alexander Goodman More, with selections from his zoological and botanical writings;

Mode of access: Internet.

J.B. Longacre print after Thomas Sully painting of Alexander Macomb [original ptg West Point Museum Art Collection, U.S. Military Academy]

Scanned to edge of engraving plate mark - NOT to edge of sheet

Impact of salinity and growth phase on alkenone distributions in coastal haptophytes

Batch cultures of Isochrysis galbana (strain CCMP 1323) and Chrysotila lamellosa (strain CCMP 1307) were grown at salinity ca. 10 to ca. 35 and the alkenone distributions determined for different growth phases. UK'37 values decreased slightly with salinity for C. lamellosa but were largely unaffected for I. galbana except during the decline phase. The values decreased with incubation time in both species. The proportion of C37:4, used as proxy for salinity, increased in both species at 0.16-0.20% per salinity unit, except during the stationary phase for I. galbana. C37:4 was much more abundant in C. lamellosa (30-44%) than in I. galbana (4-12%). Although our results suggest that salinity has a direct effect on alkenone distributions, growth phase and species composition will also have a marked impact, complicating the use of alkenone distributions as a proxy for salinity in the marine environment.

Alkyl radical geometry controls geminate cage recombination in alkylcobalamins

Abstract: The radical pair that results from photolysis of adenosylcob(II1)alamin (AdoCbl"') undergoes primary geminate recombination with a first-order rate constant of 1 x lo9 s-l. In contrast, methylcob(II1)alamin (CH3Cbl"') and aristeromicylcob(II1)alamin (AriCblII', the carbocyclic analogue of AdoCbl"' in which the ribofuranose ring oxygen has been replaced with a methylene group) does not undergo primary geminate recombination. The ribofwanose group enables a high rate of geminate recombination in the [Ado' Cbl"'] radical pair. This may be due to a stereoelectronic (p-anomeric) effect that maintains a pyramidal geometry at the 5'-carbon of the 5'-deoxyadenosyl radical, or it may be due to hindered rotation about the C4t-C5, bond such that /?-elimination to the olefin is prevented. Recombination in the geminate singlet radical pair is in competition with diffusive escape to form a solvent-separated radical pair. Hyperfine coupling from Co" promotes intersystem crossing to the triplet radical pair (Chagovetz, A. M.; Grissom, C. B. J. Am. Chem. SOC. 1993, 115, 12152). Recombination of the [CH3' Cbl"] radical pair is not prevented by a lack of intersystem crossing, as neither unlabeled or I3C-labeled CH3Cbl"' undergoes geminate recombination. There is only a small difference in the rate of diffusive recombination in the solvent cage for AdoCbl"', AriCbl"', and CH3Cbl"' following photolysis: 2.01 x 10" s-l, 2.20 x lo4 s-l, and 1.16 x lo4 s-l. The rate of diffusive recombination is limited by productive collisions and not by radical geometry or intersystem crossing. The CF3' radical that results from photolysis of (trifluoromethyl)cob(III)alamin (CF3Cbl"') maintains its pyramidal geometry and undergoes faster diffusive recombination in the solvent cage at 51 x lo4 s-l. The C-Co bond dissociation enthalpy in AriCbl"' is 37 f 1.4 kcaymol. The profound difference in geminate recombination rates for AdoCbl"' and CH3Cbl"' is consistent with their different biological roles as enzymatic cofactors: AdoCbl"' is an initiator of radical chain chemistry in the active site, whereas CH3Cbl"' is a methyl group donor in an S~2-type process.

Fragmentation pathways of 2,3-dimethyl-2,3-dinitrobutane cations in the gas phase

2,3-Dimethyl-2,3-dinitrobutane (DMNB) is an explosive taggant added to plastic explosives during manufacture making them more susceptible to vapour-phase detection systems. In this study, the formation and detection of gas-phase \[M+H](+), \[M+Li](+), \[M+NH(4)](+) and \[M+Na](+) adducts of DMNB was achieved using electrospray ionisation on a triple quadrupole mass spectrometer. The \[M+H](+) ion abundance was found to have a strong dependence on ion source temperature, decreasing markedly at source temperatures above 50 degrees C. In contrast, the \[M+Na](+) ion demonstrated increasing ion abundance at source temperatures up to 105 degrees C. The relative susceptibility of DMNB adduct ions toward dissociation was investigated by collision-induced dissociation. Probable structures of product ions and mechanisms for unimolecular dissociation have been inferred based on fragmentation patterns from tandem mass (MS/MS) spectra of source-formed ions of normal and isotopically labelled DMNB, and quantum chemical calculations. Both thermal and collisional activation studies suggest that the \[M+Na](+) adduct ions are significantly more stable toward dissociation than their protonated analogues and, as a consequence, the former provide attractive targets for detection by contemporary rapid screening methods such as desorption electrospray ionisation mass spectrometry. Copyright (C) 2009 Commonwealth of Australia. Published by John Wiley & Sons, Ltd.

Faecal incontinence in childhood : a multidisciplinary approach including biofeedback

One hundred and seven children with faecal incontinence were evaluated and managed over a 3 year period by a multidisciplinary team. After initial clinical assessment, evaluation of defaecatory mechanisms (using a balloon model) and assessment of personal-social development and self-concept were undertaken. Management was based on initial bowel evacuation, short-term laxatives, and habit training involving systematic use of positive reinforcement; 69 children received biofeedback conditioning. Idiopathic megacolon with constipation and soiling was the most common finding (98 cases). Other diagnoses included previously undiagnosed neurogenic bowel (three cases), post-surgical anal anomalies (four cases), and psychogenic encopresis (two cases). Idiopathic megacolon was characterized by decreased rectal sensation, increased threshold for external sphincter relaxation and an inability to evacuate. Faecal incontinence was associated with an undesirably low social self-concept (70% of the 40 evaluated), but was not related to a delay in development (mean general developmental quotient = 105 ± 8, for the 35 tested). Family psychopathology warranting referral for family therapy was found in 14 children (13%). The management programme yielded a short-term (3 months) cure rate of 68% and a long-term (12 months) cure rate of 90%, with 10% having continued soiling which varied from occasional to several incidents/week. No significant improvement in self-concept was observed overall, although marked improvements were observed in some children. We conclude that disordered defaecatory dynamics are a major determinant of faecal incontinence in children. Undesirably low social self-concepts but normal developmental ability accompany this condition. Management is facilitated by a multidisciplinary approach, acknowledging the role of both behavioural and physiological components of the problem. This approach is effective in eradicating soiling in the majority of cases, comparing favourably with other published data.

Genome-wide meta-analysis identifies new susceptibility loci for migraine

Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P<5x10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

Correlation of TACC3, FGFR3, MMSET and p21 expression with the t(4;14)(p16.3;q32) in multiple myeloma

The t(4;14)(p16;q32) translocation seen in c. 18% of newly diagnosed multiple myeloma (MM) cases, results in FGFR3 activation and creation of an IGH/MMSET fusion transcript. We have recently shown that FGFR3 is activated in only 75% of t(4;14)(+) cases, suggesting that alternative genes near the breakpoint may be involved in the transforming event. The gene, TACC3, located just 50 kb telomeric of FGFR3, with transforming capacity, therefore represented a candidate gene. Using a real-time quantitative polymerase chain reaction-based approach on a cohort of 54 patients, we found a statistically significant, twofold increase in TACC3 expression in t(4;14)(+) cases. TACC3, MMSET and p21 values were positively correlated in all cases and, of particular interest, six patient samples [three t(4;14)(-), three t(4;14)(+)] samples showed a joint up-regulation of TACC3, MMSET and p21. Although a poor prognosis is linked with elevated MMSET expression, an extended follow-up period will be required to evaluate the significance of elevated TACC3 and p21 expression in this subgroup of MM.

Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis

We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P <5 × 10(-8)), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r(2) > 0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r(2) > 0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.

Changes in natural killer cells, the CD57CD8 subset, and related cytokines in healthy aging

Aging has been shown to be accompanied by various changes in the lymphocyte subset distribution in the elderly. We have investigated more fully, and in a large number of subjects, age-related changes within several subpopulations bearing natural killer (NK) cell-associated surface antigens and changes in several cytokines involved in NK cell expansion. A total of 229 healthy subjects from all decades of life from 20 to 98 years of age was included in this cross-sectional study. A significant increase with age was found in both the absolute counts and the proportions of CD3-CD(16+56)+, CD3+CD(16+56)+, CD57+CD8+, CD57+CD8(low)+, and CD57+CD8- cells, whereas the CD57+CD8(high)+ subset, which may represent the cytolytic T cell population more precisely, showed less change with age. Some evidence is also provided to suggest that these expanded NK cell populations are in an activated state. Soluble IL-2 receptor levels were also found to increase significantly with age and correlated with certain NK cell subsets. Although the functions of some of these subsets remain to be elucidated, their expansion in the elderly may represent a remodeling of the immune system with increasing age, with an increase in non-MHC-restricted cells perhaps compensating for the previously reported decline in T and B cells in the elderly. Alternatively, increased numbers of these cells may be a direct result of cytokine dysregulation or increased antigenic or neoplastic cell challenge.

Preoperative radial artery volume flow is predictive of arteriovenous fistula outcomes

Objective: Guidelines recommend the creation of a wrist radiocephalic arteriovenous fistula (RAVF) as initial hemodialysis vascular access. This study explored the potential of preoperative ultrasound vessel measurements to predict AVF failure to mature (FTM) in a cohort of patients with end-stage renal disease in Northern Ireland

.Methods: A retrospective analysis was performed of all patients who had preoperative ultrasound mapping of upper limb blood vessels carried out from August 2011 to December 2014 and whose AVF reached a functional outcome by March 2015.

Results: There were 152 patients (97% white) who had ultrasound mapping andan AVF functional outcome recorded; 80 (54%) had an upper arm AVF created, and 69 (46%) had a RAVF formed. Logistic regression revealed that female gender (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.12-5.55; P = .025), minimum venous diameter (OR, 0.6; 95% CI, 0.39-0.95; P = .029), and RAVF (OR, 0.4; 95% CI, 0.18-0.89; P = .026) were associated with FTM. On subgroup analysis of the RAVF group, RAVFs with an arterial volume flow <50 mL/min were seven times as likely to fail as RAVFs with higher volume flows (OR, 7.0; 95% CI, 2.35-20.87; P < .001).

Conclusions: In this cohort, a radial artery flow rate <50 mL/min was associated with a sevenfold increased risk of FTM in RAVF, which to our knowledge has not been previously reported in the literature. Preoperative ultrasound mapping adds objective assessment in the clinical prediction of AVF FTM.

El rechazo entre iguales y la comprensión infantil de los estados mentales.

Analizar cómo las experiencias sociales dentro del sistema de iguales se relacionan con la comprensión de los estados mentales infantiles, adoptando un punto de vista teórico socio-cultural. En concreto: explorar la influencia de ciertas variables control (personales y familiares) en la comprensión de la mente por parte del sujeto. Examinar la posición del grupo sociométrico de rechazados respecto a las variables de control. Analizar la naturaleza de la comprensión de la mente en un grupo sociométrico que presenta una interacción inadecuada con los iguales: los rechazados. Comprobar qué factores pueden estar afectando a la comprensión de la mente del grupo de los sujetos rechazados. De 310 alumnos de 15 clases de P4, P5 y primero de primaria de la provincia de Castellón se escogieron 105, de los cuales, 35 eran rechazados, 34 populares y 36 medios. Al año siguiente se volvieron a pasar las tareas a la misma muestra, ahora de P5, 1õ y 2õ de primaria. De 307 sujetos (hubo mortalidad de tres sujetos respecto al año anterior por que cambiaron de colegio) se escogieron 95, de los cuales, 27 eran rechazados, 26 populares y 42 medios. Primero se pasa el cuestionario sociométrico a los 310 alumnos, para asignarlos a las distintas categorías sociométricas (rechazado, popular y medio, variables dependientes), y se comprueba que cumplen los requisitos cognitivos básicos. Después se equiparan los grupos en inteligencia general y verbal, y luego se administran las tareas experimentales (cuyos resultados son las variables independientes), individualmente y en horario escolar, bajo consentimiento previo de los padres. Al cabo de un año se vuelve a administrar el cuestionario sociométrico a la misma muestra (307 sujetos) para volver a agruparlos en categorías y administrar las tareas experimentales. Las tareas de comprensión de la mente que se administraron son: la tarea de la creencia falsa de primer orden y la de segundo orden; tarea de engaño; historias extrañas y la tarea emocional. También se administra el Pupil Evaluation Inventory, en versión abreviada. Se utilizan: el test de Tukey para los análisis post-hoc, el índice de concordancia kappa para conocer la estabilidad de los grupos sociométricos, el análisis de frecuencia de aparición de sesgos interpretativos en la tareas de historias extrañas y la prueba T para hacer una comparación entre las tareas. Los sujetos rechazados no parecen tener una peor actuación que el resto de grupos sociométricos al entender los estados mentales de los demás (tarea de la falsa creencia), pero sí empeora a la hora de manipular estos estados mentales de los demás para conseguir sus deseos (tarea de engaño). Parecen comprender peor cuál es la intención del hablante, sobre todo si resulta contradictoria con otro tipo de mensajes, como la expresión facial o el contexto. El nivel de comprensión de las emociones y sus causas no arroja ninguna diferencia entre los sujetos rechazados y los populares o medios. Por lo que se refiere a las variables de control se encuentra gran influencia de las variables edad cronológica, autoconcepto y cociente intelectual. La variable género presenta conexiones con algunas tareas, siempre a favor del género femenino. No se encontró un efecto facilitador del número de hermanos en la comprensión de la mente, pero se encontraron efectos indirectos que acentuaban el carácter negativo de convivir únicamente con 2-3 personas en la casa. Por otro lado, los sujetos rechazados presentaron una probabilidad mayor de pertenecer a familias numerosas y de encontrarse en los últimos lugares de nacimiento, pero sólo apareció en los sujetos mayores de 6 años. El tipo de interacción que presentan los sujetos rechazados parece condicionar su comprensión de determinadas habilidades mentalistas, como por ejemplo el engaño o los aspectos intencionales de la comunicación.