Elevated circulating sclerostin concentrations in individuals with high bone mass, with and without LRP5 mutations

CONTEXT: The role and importance of circulating sclerostin is poorly understood. High bone mass (HBM) caused by activating LRP5 mutations has been reported to be associated with increased plasma sclerostin concentrations; whether the same applies to HBM due to other causes is unknown. OBJECTIVE: Our objective was to determine circulating sclerostin concentrations in HBM. DESIGN AND PARTICIPANTS: In this case-control study, 406 HBM index cases were identified by screening dual-energy x-ray absorptiometry (DXA) databases from 4 United Kingdom centers (n = 219 088), excluding significant osteoarthritis/artifact. Controls comprised unaffected relatives and spouses. MAIN MEASURES: Plasma sclerostin; lumbar spine L1, total hip, and total body DXA; and radial and tibial peripheral quantitative computed tomography (subgroup only) were evaluated. RESULTS: Sclerostin concentrations were significantly higher in both LRP5 HBM and non-LRP5 HBM cases compared with controls: mean (SD) 130.1 (61.7) and 88.0 (39.3) vs 66.4 (32.3) pmol/L (both P < .001, which persisted after adjustment for a priori confounders). In combined adjusted analyses of cases and controls, sclerostin concentrations were positively related to all bone parameters found to be increased in HBM cases (ie, L1, total hip, and total body DXA bone mineral density and radial/tibial cortical area, cortical bone mineral density, and trabecular density). Although these relationships were broadly equivalent in HBM cases and controls, there was some evidence that associations between sclerostin and trabecular phenotypes were stronger in HBM cases, particularly for radial trabecular density (interaction P < .01). CONCLUSIONS: Circulating plasma sclerostin concentrations are increased in both LRP5 and non-LRP5 HBM compared with controls. In addition to the general positive relationship between sclerostin and DXA/peripheral quantitative computed tomography parameters, genetic factors predisposing to HBM may contribute to increased sclerostin levels.

Improving diagnosis of tumor-induced osteomalacia with gallium-68 DOTATATE PET/CT

Context: Tumor-induced osteomalacia (TIO) is a rarely diagnosed disorder presenting with bone pain, fractures, muscle weakness, and moderate-to-severe hypophosphatemia resulting from fibroblast growth factor 23-mediated renal phosphate wasting. Tumors secreting fibroblast growth factor 23 are often small and difficult to find with conventional imaging. Objective: We studied the utility of 68Ga-DOTA-octreotate (DOTATATE) somatostatin receptor positron emission tomography (PET)/computed tomography (CT) imaging in the diagnosis of TIO. Design and Setting: A multicenter case series was conducted at tertiary referral hospitals. Patients and Methods: Six patients with TIO diagnosed between 2003 and 2012 in Australia were referred for DOTATATE PET imaging. We reviewed the clinical history, biochemistry, imaging characteristics, histopathology, and clinical outcome of each patient. Results: Each case demonstrated delayed diagnosis despite severe symptoms. DOTATATE PET/CT imaging demonstrated high uptake and localized the tumor with confidence in each case. After surgical excision, there was resolution of clinical symptoms and serum phosphate, except in one patient who demonstrated residual disease on PET/CT. All tumors demonstrated high somatostatin receptor subtype 2 cell surface receptor expression using immunohistochemistry. Conclusions: In patients with TIO, DOTATATE PET/CT can successfully localize phosphaturic mesenchymal tumors and may be a practical first step in functional imaging for this disorder. Serum phosphate should be measured routinely in patients with unexplained muscle weakness, bone pain, or stress fractures to allow earlier diagnosis of TIO. - See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2012-3642#sthash.eXD0CopL.dpuf

Pheo-type: A diagnostic gene-expression assay for the classification of pheochromocytoma and paraganglioma

Context: Pheochromocytomas and paragangliomas (PPGLs) are heritable neoplasms that can be classified into gene-expression subtypes corresponding to their underlying specific genetic drivers. Objective: This study aimed to develop a diagnostic and research tool (Pheo-type) capable of classifying PPGL tumors into gene-expression subtypes that could be used to guide and interpret genetic testing, determine surveillance programs, and aid in elucidation of PPGL biology. Design: A compendium of published microarray data representing 205 PPGL tumors was used for the selection of subtype-specific genes that were then translated to the Nanostring gene-expression platform. A support vector machine was trained on the microarray dataset and then tested on an independent Nanostring dataset representing 38 familial and sporadic cases of PPGL of known genotype (RET, NF1, TMEM127, MAX, HRAS, VHL, and SDHx). Different classifier models involving between three and six subtypes were compared for their discrimination potential. Results: A gene set of 46 genes and six endogenous controls was selected representing six known PPGL subtypes; RTK1–3 (RET, NF1, TMEM127, and HRAS), MAX-like, VHL, and SDHx. Of 38 test cases, 34 (90%) were correctly predicted to six subtypes based on the known genotype to gene-expression subtype association. Removal of the RTK2 subtype from training, characterized by an admixture of tumor and normal adrenal cortex, improved the classification accuracy (35/38). Consolidation of RTK and pseudohypoxic PPGL subtypes to four- and then three-class architectures improved the classification accuracy for clinical application. Conclusions: The Pheo-type gene-expression assay is a reliable method for predicting PPGL genotype using routine diagnostic tumor samples.

Predictors of violent reconvictions and mortality among impulsive alcoholic violent offenders: A prospective study

Acts of violence lays a great burden on humankind. The negative effects of violence could be relieved by accurate prediction of violent recidivism. However, prediction of violence has been considered an inexact science hampered by scare knowledge of its causes. The study at hand examines risk factors of violent reconvictions and mortality among 242 Finnish male violent offenders exhibiting severe alcoholism and severe externalizing personality disorders. The violent offenders were recruited during a court-ordered 2-month inpatient mental status examination between 1990—1998. Controls were 1210 individuals matched by sex-, age-, and place of birth. After a 9-year non-incarcerated follow-up criminal register and mortality data were obtained from national registers. Risk analyses were applied to estimate odds and relative risk for recidivism and mortality. Risk variables that were included in the analyses were antisocial personality disorder (ASPD), borderline personality disorder (BPD), a comorbidity of ASPD and BPD, childhood adversities, alcohol consumption, age, and monoamine oxidase A (MAOA) genotype. In addition to risk analyses, temperament dimensions (Tridimensional Personality Questionnaire [TPQ]) were assessed. The prevalence of recidivistic acts of violence (32%) and mortality (16%) was high among the offenders. Severe personality disorders and childhood adversities increased the risk for recidivism and mortality both among offenders (OR 2.0–10.4) and in comparison between offenders and controls (RR 4.3–53.0). Offenders having BPD and a history of childhood maltreatment emerged as a group with a particularly poor prognosis. MAOA altered the effects of alcohol consumption and ageing. Alcohol consumption (+2.3%) and age (–7.3%) showed significant effects on the risk for violent reconvictions among the high activity MAOA (MAOA-H) offenders, but not among the low activity MAOA (MAOA-L) offenders. The offenders featured temperament dimensions of high novelty seeking, high harm avoidance, and low reward dependence matching Cloninger’s definition of explosive personality. The fact that the risk for recidivistic acts of violence and mortality accumulated into clearly defined subgroups supports future efforts to provide for evidence based violence prevention and risk assessments among violent offenders.

The Raman spectrum of cyclohexanol

The Raman spectrum of cyclohexanol has been studied in detail in the liquid state at 30° C. and at about 68° C. and in the solid state at about 13° C. The O-H stretching frequency of cyclohexanol has been found to extend from 3106-3571 cm.-1 in the liquid state at 30° C. and from 3204-3652 cm.-1 at 68° C. The 38 lines recorded in the present investigation have been following frequency shifts: 342, 408, 458, 478, 555, 653, 789, 834, 843, 863, 887, 920, 966, 978, 1024, 1047, 1070, 1139, 1173, 1184, 1210, 1235, 1252, 1301, 1329, 1346, 1362, 1438, 1448, 1464, 2660, 2684, 2710, 2854, 2896, 2925, 2940, 3106 to 3511 (band). Those lines which are italicized are the additional lines observed for the first time. The Raman lines at 966 cm.-1 and 1070 cm.-1 have been assigned to C-OH stretching vibrations of the axial and equatorial isomers. The ratio of the integrated intensity of the 1070 cm.-1 line to the 966 cm.-1 gave the equilibrium constant K as 2·896 at 30° C. and as 2·66 at 68° C. Knowing K, the free energy different Δ F was calculated and it was found to be 0·64 Kcal./mole at 30° C. and 0·66 Kcal./mole at about 68° C. Reasonable assignment has been made for most of the observed Raman lines.

An online-implementable differential evolution tuned all-aspect guidance law

This paper proposes a differential evolution based method of improving the performance of conventional guidance laws at high heading errors, without resorting to techniques from optimal control theory, which are complicated and suffer from several limitations. The basic guidance law is augmented with a term that is a polynomial function of the heading error. The values of the coefficients of the polynomial are found by applying the differential evolution algorithm. The results are compared with the basic guidance law, and the all-aspect proportional navigation laws in the literature. A scheme for online implementation of the proposed law for application in practice is also given. (c) 2010 Elsevier Ltd. All rights reserved.

A Comparative Study of Electrical Switching Behavior of Certain Tellurium based Chalcogenide Thin Films for Phase Change Memory (PCM) Applications

This work describes the electrical switching behavior of three telluride based amorphous chalcogenide thin film samples, Al-Te, Ge-Se-Te and Ge-Te-Si. These amorphous thin films are made using bulk glassy ingots, prepared by conventional melt quenching technique, using flash evaporation technique; while Al-Te sample has been coated in coplanar electrode geometry, Ge-Se-Te and Ge-Te-Si samples have been deposited with sandwich electrodes. It is observed that all the three samples studied, exhibit memory switching behavior in thin film form, with Ge-Te-Si sample exhibiting a faster switching characteristic. The difference seen in the switching voltages of the three samples studied has been understood on the basis of difference in device geometry and thickness. Scanning electron microscopic image of switched region of a representative Ge15Te81Si4 sample shows a structural change and formation of crystallites in the electrode region, which is responsible for making a conducting channel between the two electrodes during switching.

Potentiometric determination of the gibbs energies of formation of SrZrO3 and BaZrO3

The Gibbs free energies of formation of strontium and barium zirconates have been determined in the temperature range 960 to 1210 K using electrochemical cells incorporating the respective alkaline-earth fluoride single crystals as solid electrolytes. Pure strontium and barium monoxides were used in the reference electrodes. During measurements on barium zirconate, the oxygen partial pressure in the gas phase over the electrodes was maintained at a low value of 18.7 Pa to minimize the solubility of barium peroxide in the monoxide phase. Strontium zirconate was found to undergo a phase transition from orthorhombic perovskite to) with space group Cmcm; D-2h(17) to tetragonal perovskite (t) having the space group 14/mcm; D-4h(18) at 1123 (+/- 10) K. Barium zirconate does not appear to undergo a phase transition in the temperature range of measurement. It has the cubic perovskite (c) structure. The standard free energies of formation of the zirconates from their component binary oxides AO (A = Sr, Ba) with rock salt (rs) and ZrO2 with monoclinic (m) structures can be expressed by the following relations:SrO (rs) + ZrO2 (m) --> SrZrO3 (o) Delta G degrees = -74,880 - 14.2T (+/-200) J mol(-1) SrO (rs) + ZrO2 (m) --> SrZrO3 (t) Delta G degrees = -73,645 - 15.3T (+/-200) J mol(-1) BaO (rs) + ZrO2 (m) --> BaZrO4 (c) Delta G degrees = -127,760 - 1.79T (+/-250) J mol(-1) The results of this study are in reasonable agreement with calorimetric measurements reported in the literature. Systematic trends in the stability of alkaline-earth zirconates having the stoichiometry AZrO(3) are discussed.

Climatic variability in Central Indian Himalaya during the last similar to 1800 years: Evidence from a high resolution speleothem record

Stable isotopes from a U/Th dated aragonite stalagmite from the Central Kumaun Himalaya provide evidence of variation in climatic conditions in the last similar to 1800 years. The delta O-18 and delta C-13 values vary from -4.3 parts per thousand to -7.6 parts per thousand and -3.4 parts per thousand to -9.1 parts per thousand respectively, although the stalagmite was not grown in isotopic equilibrium with cave drip water, a clear palaeoclimatic signal in stalagmite delta O-18 values is evident based on the regional climate data. The stalagmite showed a rapid growth rate during 830-910 AD, most likely the lower part of Medieval Warm Period (MWP), and 1600-1640 AD, the middle part of Little Ice Age (LIA). Two distinct phases of reduced precipitation are marked by a 2 parts per thousand shift in 8180 values towards the end of MWP (similar to 1080-1160 AD) and after its termination from similar to 1210 to 1440 AD. The LIA (similar to 1440-1880 AD) is represented by sub-tropical climate similar to modern conditions, whereas the post-LIA was comparatively drier. The Inter Tropical Convergence Zone (ITCZ) was located over the cave location during wetter/warmer conditions. When it shifted southward, precipitation over the study area decreased. A prominent drop in delta O-18 and delta C-13 values during the post-LIA period may also have been additionally influenced by anthropogenic activity in the area. (C) 2013 Elsevier Ltd and INQUA. All rights reserved.

Construction of Block Orthogonal STBCs and Reducing Their Sphere Decoding Complexity

Construction of high rate Space Time Block Codes (STBCs) with low decoding complexity has been studied widely using techniques such as sphere decoding and non Maximum-Likelihood (ML) decoders such as the QR decomposition decoder with M paths (QRDM decoder). Recently Ren et al., presented a new class of STBCs known as the block orthogonal STBCs (BOSTBCs), which could be exploited by the QRDM decoders to achieve significant decoding complexity reduction without performance loss. The block orthogonal property of the codes constructed was however only shown via simulations. In this paper, we give analytical proofs for the block orthogonal structure of various existing codes in literature including the codes constructed in the paper by Ren et al. We show that codes formed as the sum of Clifford Unitary Weight Designs (CUWDs) or Coordinate Interleaved Orthogonal Designs (CIODs) exhibit block orthogonal structure. We also provide new construction of block orthogonal codes from Cyclic Division Algebras (CDAs) and Crossed-Product Algebras (CPAs). In addition, we show how the block orthogonal property of the STBCs can be exploited to reduce the decoding complexity of a sphere decoder using a depth first search approach. Simulation results of the decoding complexity show a 30% reduction in the number of floating point operations (FLOPS) of BOSTBCs as compared to STBCs without the block orthogonal structure.

爆炸应力波在各向同性损伤岩石中的衰减规律研究

通过对一维应力波在Hopkinson压杆之间的试件内的衰减及折反射关系分析，导出了衰减率 的表达式，然后对含损伤的岩石试件进行冲击实验，得到了衰减率与初始损伤的关系式，从而提供了一种测定衰减率的实验方法。通过应力等效模拟，得到了球面与柱面爆炸应力波的衰减规律。

Caracterización de la finca Santa Rosa en el Municipio de Tola, Rivas, Nicaragua

Con el propósito de caracterizar una finca que posee uno de los pocos núcleos existentes de ganado Reyna, se escogió la Finca Sta. Rosa del municipio de Tola. La información se recogió mediante un diagnóstico estático en el que se realizaron encuestas, en la finca Santa Rosa así como en las fincas ganaderas aledañas, comprendiendo los componentes suelo, pasto, animal y climáticos. Un diagnóstico dinámico en la finca Sta. Rosa durante el periodo Mayo 91 - Enero 92 el cual comprendía la recopilación de información financiera, productiva y reproductiva del hato, incluyendo estimaciones mensuales de la calidad y disponibilidad del pasto, dos días antes del las mediciones de leche, a través del método 'Doble muestreo', Los resultados indican que la unidad de producción sta Rosa y demás fincas ganaderas del municipio de Tola poseen poco movimiento de capital, su sistema de explotación es extensivo de doble propósito. Los principales grupos raciales son cruces de Brahmán con los genotipos siguientes; Pardo Suizo, Holstein y Reyna, predominando la sangre Brahmán. La zona de vida es trópico seco premontano. Los principales índices zootécnicos encontrados el núcleo de ganado Reyna y demás fincas aledañas son similares, encontrándose ambos por debajo del nivel establecido por el en explotaciones de este tipo, afectando negativamente asi la rentabilidad de éstas. Los promedios de las variables PL305, LARLA, e IPP encontrados en el Núcleo Reyna son estadísticamente similares para los factores número y época de parto. Obteniéndose promedios mínimo cuadráticos de: 1181.6+- 30.9 Kg, 291.7+- 4.4 días, 478.23+-9,4 días respectivamente, y promedio de PLD de 4.24 +- 0.02 Kg. La calidad de los pastos es baja, llegando en 2 de los meses cri ticos de la época seca a encontrarse PB% de 3.27 y PLD promedio de 3.86 Kg. Los promedios para MS, PB y disponibilidad de los pastos muestreados fueron 24.63%, 7.35% y 7172.78 Kg MS/potrero respectivamente del d:l.a de muestreo. Los resultados de análisis del suelo mostraron bajos porcentajes de materia seca, bajos valores de macroelementos (N, P), un pH ligeramente ácido (6.2.), y una textura franco arcilloso concluyendo que los factores limitantes son periodo seco acentuado, baja fertilidad de los suelos, baja calidad de los pastos y un manejo del hato inadecuado.

Adaptacion de cuatro lineas de alfalfa forrajera (Medicago sativa L.) a las condiciones climaticas de la Hacienda Las Mercedes, campo y vivero

Con el objeto de evaluar el comportamiento adaptativo de cuatro líneas de alfalfa (Medicago sativa L.) en condiciones de campo y de vivero, se realizó un estudio en la Hacienda Las Mercedes, propiedad de la Universidad Nacional Agraria, ubicada en la ciudad de Managua Km 11 carretera norte, , entrada al CARNIC 2 km al lago. Teniendo su ubicación geográfica en un cuadrante con las siguientes coordenadas: 12°10'14"a 12"08'05" en latitud Norte y 86.10'22" a 86"09'44" longitud Oeste. El estudio se realizó en dos fuses 1) de campo y 2) en vivero. En ambos se determinó el grado de adaptación de cuatro líneas de alfalfa (Medicago sativa L.), tres procedentes de Texas-EE UU (8L418, 105916 y 9818) y una de Sébaco-Nicaragua (l3-A50) donde se ha establecido por más de tres años. El ensayo de campo se estableció en un área que anteriormente fue utilizada para la siembra de sorgo forrajero y el de vivero se realizó en el vivero de la UNA, en la misma finca. Se consideró cada una de las líneas como tratamiento. El Diseño experimental usado para ambas fases fue de bloques completos al azar (BCA), con 4 repeticiones. En campo con parcelas experimentales fueron de 4 m2 (2 m x 2 m), para un área total de 120m2 Se sembraron 6 surcos a una distancia de 30 cm entre surco y 14 plantas por surcos distanciados a 15 cm. Se realizó análisis de varianza utilizando programa SAS versión 99, cuando se encontró diferencias significativas o altamente significativas para tratamientos se realizaron pruebas de medias según Duncan. El terreno se preparó de forma convencional, con una chapea inicial, un paso de arado y gradeo de forma mecanizada, posteriormente se realizó la estructuración del diseño de campo. Las variables evaluadas según las condiciones de campo fueron: germinación, altura de la plantas, daños por plaga y enfermedades y ramificación, en las condiciones de vivero fueron: germinación, sobrevivencia, altura (cm), daños por plagas y enfermedades. Como resultado se obtuvo que 3 de las líneas presentaron buena germinación en condiciones de campo y vivero siendo la de mejor comportamiento la línea 13A-50 con un promedio del 97%. Para altura la línea 9818 presentó el mejor comportamiento en condiciones de campo con rangos de 48cm - 58 cm manteniendo superioridad durante el estudio en comparación con el resto de las líneas evaluadas. En daños por plagas la línea 8L418 la de menor afectación, y la más afectada fue la línea l3A-50. En daños por enfermedades la línea 9818 obtuvo los mayores daños en los niveles de moderado a muy grave y la línea l3A-50 fue la de menor incidencia. Todas las líneas presentaron una ramificación media de 30%, siendo la línea 105916 la de mejor comportamiento. En vivero la línea l3A-50 presentó la mejor altura. La línea 9818 fue la de mejor adaptabilidad en condiciones de campo, seguida de la línea BA-50. Pero en condiciones de vivero la línea 13A-50 fue la de mejor adaptabilidad, seguida de la línea 8L418.en resumen la línea l3A-50 fue la de mejor comportamiento adaptativo.