bluuebunny/crossref_metadata_2025 huggingface dataset:
How I treat relapsed myeloma
Authors: Bladé Joan , Rosiñol Laura , Fernández de Larrea Carlos
Published: January 2015

Multiple myeloma (MM) is a plasma cell malignancy leading to significant life-expectancy shortening. Although the incorporation of the novel agents thalidomide, bortezomib, and lenalidomide in the front-line therapy has resulted in significant improvement, almost all patients relapse, making the treatment of relapse a real challenge. In the present article, when and how to treat relapsed MM is discussed. Treatment can be safely delayed in a subset of patients with asymptomatic relapse, whereas those with symptomatic relapse, advanced disease at diagnosis, or significant paraproteinemic increase require prompt rescue therapy. The benefit of retreatment and the use of a sequential approach for successive relapses considering drug synergism are highlighted. For patients with aggressive relapses and for those who have exhausted all available options, continued therapy until disease progression is recommended, particularly when using regimens with a long-term safety profile. Patients with a duration response to a first autologous stem cell transplantation (ASCT) longer than 2 years may benefit from a second ASCT. Patients with aggressive disease and/or poor cytogenetics at diagnosis relapsing within the first 2 years from ASCT should be considered for an allogeneic transplantation. Finally, a number of newer promising drugs are being actively investigated and the enrolment of patients in clinical trials is encouraged.
Activated factor XI increases the procoagulant activity of the extrinsic pathway by inactivating tissue factor pathway inhibitor
Authors: Puy Cristina , Tucker Erik I. , Matafonov Anton , Cheng Qiufang , Zientek Keith D. , Gailani Dave , Gruber András , McCarty Owen J. T.
Published: January 2015

Key Points

Activated factor XI binds and proteolyzes tissue factor pathway inhibitor. Activated factor XI promotes factor X activation generation and fibrin formation through the inactivation of tissue factor pathway inhibitor from platelets and on endothelial cells.
Long-term donepezil use for dementia with Lewy bodies: results from an open-label extension of Phase III trial
Authors: Mori Etsuro , Ikeda Manabu , Nagai Reiko , Matsuo Kazutaka , Nakagawa Masaki , Kosaka Kenji
Published: January 2015

Introduction

The long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial.

Methods

This 52-week study consisted of 16-week randomized placebo-controlled (RCT) and 36-week open-label extension phases. Of 142 DLB patients enrolled in the RCT phase (three arms: placebo, 5 mg, and 10 mg), 110 entered the extension phase. The placebo group of the RCT phase initiated active treatment at week 16, and the active groups maintained allocated treatment and dosages until week 24. After week 24, all patients received 10 mg. Dose reduction to 5 mg for safety concerns was allowed. Efficacy measures included Mini-Mental State Examination (MMSE) for cognitive function and Neuropsychiatric Inventory (NPI) for behavioral symptoms. Safety evaluations included adverse events (AEs) and the unified Parkinson disease rating scale.

Results

In total, 100 subjects completed the study. Cognitive function improvement was sustained for 52 weeks (MMSE at week 52 in 10 mg: 2.8 ± 3.5 (mean ± standard deviation); P <0.001, Student paired t test)). Those who received placebo in the RCT phase showed an improvement after starting active treatment. NPI improved in all the groups throughout the study, including the placebo period. In the subgroup of the 5 mg group without remarkable cognitive or behavioral improvement at week 24, further improvement was observed after a dose increase to 10 mg. After week 24, 21 patients experienced dose reduction. The incidence of any AEs did not increase over time.

Conclusions

The long-term administration of donepezil at 10 mg/day improved cognitive function for up to 52 weeks in patients with DLB without increasing the risk of clinically significant safety events.

Trial registration

NCT01278407. Trial registration date: January 14, 2011.
The monoaminergic footprint of depression and psychosis in dementia with Lewy bodies compared to Alzheimer’s disease
Authors: Vermeiren Yannick , Van Dam Debby , Aerts Tony , Engelborghs Sebastiaan , Martin Jean-Jacques , De Deyn Peter P
Published: January 2015

Introduction

Depression and psychosis are two of the most severe neuropsychiatric symptoms (NPS) in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). Both NPS have negative effects on cognitive performance and life expectancy. The current study aimed to investigate and compare monoaminergic etiologies between both neurodegenerative conditions, given the lack of an efficient pharmacological treatment until present.

Methods

Eleven behaviorally relevant brain regions of the left frozen hemisphere of 10 neuropathologically confirmed AD patients with/without depression (AD + D/-D; 5 were psychotic within AD + D), 10 confirmed DLB patients, all of whom were depressed (DLB + D; 5 psychotic patients), and, finally, 10 confirmed control subjects were regionally dissected. All patients were retrospectively assessed before death using the Behavioral Pathology in Alzheimer’s Disease Rating Scale (Behave-AD) and Cornell Scale for Depression in Dementia amongst others. The concentrations of dopamine (DA), serotonin (5-HT), (nor)adrenaline and respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA), and, 3-methoxy-4-hydroxyphenylglycol (MHPG), were determined using reversed-phase high-performance liquid chromatography with electrochemical detection.

Results

DLB subjects had the overall lowest monoamine and metabolite concentrations regarding 33 out of 41 significant monoaminergic group alterations. Moreover, MHPG levels were significantly decreased in almost 8 out of 11 brain regions of DLB- compared to AD patients. We also observed the lowest 5-HT and 5-HIAA levels, and 5-HIAA/5-HT turnover ratios in DLB + D compared to AD + D subjects. Additionally, a 4- and 7-fold increase of DOPAC/DA and HVA/DA turnover ratios, and, a 10-fold decrease of thalamic DA levels in DLB + D compared to AD + D patients and control subjects was noticed. Regarding psychosis, hippocampal DA levels in the overall DLB group significantly correlated with Behave-AD AB scores. In the total AD group, DA levels and HVA/DA ratios in the amygdala significantly correlated with Behave-AD AB scores instead.

Conclusions

Monoaminergic neurotransmitter alterations contribute differently to the pathophysiology of depression and psychosis in DLB as opposed to AD, with a severely decreased serotonergic neurotransmission as the main monoaminergic etiology of depression in DLB. Similarly, psychosis in DLB might, in part, be etiologically explained by dopaminergic alterations in the hippocampus, whereas in AD, the amygdala might be involved.
Linear complementarity problem: A novel approach to design finite-impulse response wavefield extrapolation filters
Authors: Naseer Muhammad Muzammal , Mousa Wail A.
Published: January 2015

In this paper, the problem of complex valued finite impulse response (FIR) wavefield extrapolation filter design was considered as a linear complementarity problem (LCP). LCP is not an optimization technique because there is no objective function to optimize; however, quadratic programming, one of the applications of LCP, can be used to find an optimal solution for the 1D FIR wavefield extrapolation filter. Quadratic programs are an extremely important source of applications of LCP; in fact, several algorithms for quadratic programs are based on LCP. We found that FIR wavefield extrapolation filter design problem can be written as a quadratic program and then, finally, to an equivalent LCP. There are two families of algorithms available to solve for LCP: (1) direct (pivoting-based) algorithms and (2) indirect (iterative) algorithms. In this study, the LCP has been solved using direct and indirect algorithms. To show the effectiveness of the proposed method, the SEG/EAGE salt velocity model data have been extrapolated via wavefield extrapolation FIR filters designed by our LCP approach, which resulted with practically stable seismic images.
Pitfalls in structural seismic interpretation due to subsalt multiples
Authors: Abriel William L.
Published: January 2015

A false structural interpretation can result from mapping coherent seismic events that are not primary reflections, but instead are multiples. It is well understood that mapping seismic events for structure is a process of tracking strong, coherent, and continuous seismic events. However, this is not a sufficient procedure for structural seismic interpretation because there can be significant coherent noise including converted waves, head waves, and multiples. These can appear strong, coherent, and continuous and so can be confused for true primaries as well as produce erroneous structural results. Subsalt multiples are an especially prevalent danger because the salt-sediment impedance contrast causes many unwanted reverberations. The pitfall of falsely mapping multiples as true structural events can be avoided using the following procedures: (1) understanding if the mapped events are structurally reasonable, (2) reviewing the geometry of stacked unmigrated time seismic sections, and (3) investigating the moveout of migrated prestack gathers.
Women With Hyperandrogenism in Elite Sports: Scientific and Ethical Rationales for Regulating
Authors: Bermon Stéphane , Vilain Eric , Fénichel Patrick , Ritzén Martin
Published: January 2015

The recent implementation by some major sports-governing bodies of policies governing eligibility of females with hyperandrogenism to compete in women’s sports has raised a lot of attention and is still a controversial issue. This short article addresses two main subjects of controversy: the existing scientific basis supporting performance enhancing of high blood T levels in elite female athletes, and the ethical rationale and considerations about these policies. Given the recently published data about both innate and acquired hyperandrogenic conditions and their prevalence in elite female sports, we claim that the high level of androgens are per se performance enhancing. Regulating women with clinical and biological hyperandrogenism is an invitation to criticism because biological parameters of sex are not neatly divided into only two categories in the real world. It is, however, the responsibility of the sports-governing bodies to do their best to guarantee a level playing field to all athletes. In order not cloud the discussions about the policies on hyperandrogenism in sports, issues of sports eligibility and therapeutic options should always be considered and explained separately, even if they may overlap. Finally, some proposals for refining the existing policies are made in the present article.
Biomass production of coppiced grey alder and the effect of fertilization
Authors: Hytönen Jyrki , Saarsalmi Anna
Published: January 2015

We studied biomass production of two naturally originated grey alder ( (L.) Moench) stands having a mixture of birch and willow located in central Finland. One of the stands was growing on a peatland site (Muhos) and the other on a mineral soil site (Juuka). The stands were clear-cut and fertilization experiments were laid out with several treatments. At Muhos, the treatments included nitrogen fertilisation with different amounts of wood ash and an unfertilized control. At Juuka, the treatments included nitrogen fertilisation either with ash or with PK, and ash and PK treatments alone and an unfertilized control. The sprouts at Muhos were grown for 17 years and at Juuka for 20 years. At Juuka the stand was clear-cut second time at the age of 20 years and grown for 8 years. The stands were measured several times and foliar samples were taken twice during the study period. Clear-cutting increased stem number manifold. The stand density of new coppiced forests after the clear-cutting decreased from 67â000â89â000 stems ha at the age of 3â6 years to 10â000â12â000 stems ha at the age of 17â20 years. On neither site fertilization affected biomass production of alders during the study period. Leafless above-ground biomass was 52â57 Mg ha after 17â20 years. Mean annual leafless above-ground biomass production (MAI) increased with increase of rotation time. At the age of 17â20 years the MAI was 2.8â3.0 Mg ha a. At Muhos, ash increased foliar P and Ca concentrations, but decreased those of Mn.Alnus incanaâ1â1â1â1
Extremal cross-polytopes and Gaussian vectors
Authors: Ambrus Gergely
Published: January 2015

For n ≥ 1, let ξ1, ..., ξn be independent, identically distributed standard normal variables. Among nonnegative real vectors u = (u1, . . . , un) of Euclidean norm 1, the quantity E∥(u1ξ1,..., unξn∥∞ is maximised when u has at most two non-zero entries, and it is minimised when u is proportional to (1,...,1). Further generalisations of this result are also discussed. As a corollary, a lower bound on the mean width of a general convex body K is derived in terms of the successive inner radii of K.
Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points
Authors: Fedosov Sergey N. , Brito Alex , Miller Joshua W. , Green Ralph , Allen Lindsay H.
Published: January 2015

A novel approach to determine vitamin B

We used a database with all four markers (n=5211) plus folate measurements (n=972). A biomarker

The predictive functions

We provide equations that combine two, three or four biomarkers into one diagnostic indicator, thereby rescaling unmatched data into the same coordinate system. Adjustment of this indicator is required if serum folate is <10 nmol/L and tHcy is measured. Revised cut-points and guidelines for using this approach are provided.
Effects of Yttrium Addition on Microstructure and Mechanical Properties of AZ80–2Sn Magnesium Alloys
Authors: Xue Hansong , Yang Gang , Li Di , Xing Zhihui , Pan Fusheng
Published: January 2015

The effects of Y on microstructure and mechanical properties of as-cast AZ80–2Sn magnesium alloys were investigated by optical microscopy, scanning electron microscopy and X-ray diffraction. Y addition not only changes the as-cast microstructure but also influences the mechanical properties of AZ80–2Sn alloy. Unmodified AZ80–2Sn alloys under casting state show that Mg17Al12 eutectic phase is semicontinuous and reticulated shape and distributes mainly at grain boundaries. Moreover, there are numerous Mg2Sn precipitate particles dispersing in Mg17Al12 eutectic phases. Y addition to as-cast AZ80–2Sn alloys has an important influence on the precipitation phase. But there has no obvious effect on grain refinement with Y addition. The results show that the AZ80–2Sn alloys with variable Y contents all contain Al2Y phase. By adding Y, the amount of Mg17Al12 is decreased and the dimension of that is reduced. Mg17Al12 eutectic phase turns to discontinuous, and the more disperse phases occur with the increase of Y content. The tensile tests indicate that a minor addition of Y can contribute to the formation of the dispersed small polygonal Al2Y particles and the improvement in the room-temperature strength. However, excessive Y addition leads to the coarsening of Al2Y phases, and thus results in the decline of strength and ductility.
Effect of Ga Addition on Morphology and Recovery of Primary Si During Al–Si Alloy Solidification Refining
Authors: Li Jingwei , Bai Xiaolong , Li Yanlei , Ban Boyuan , Chen Jian
Published: January 2015

The effect of Ga addition on alloy macrostructure, morphology and recovery rate of primary Si during the Al–Si–Ga alloy solvent refining process of silicon was studied in this work. The addition of Ga to Al–Si alloy could change the morphology of the primary Si. The average plate thickness of the primary Si increases with increase of Ga content. With the increase of Ga content, the average plate length of the primary Si crystals becomes larger when the Ga content is less than 5% in the Al–30%Si–xGa alloy, but becomes smaller when the Ga content exceeds 5%. Al–Si–Ga alloys consist of three types, primary Si, Ga
x
Al1–x
, (α-Al+Si+β-Ga) eutectic. (111) is the preferred growth surface of the plate-like primary Si. The recovery rate of the primary Si increases with the increase of Ga content. When the Ga content increased to 20% in Al–30%Si–xGa alloy, the relative recovery rate of the primary Si increased to 50.41% than that in Al–30%Si alloy.
Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques
Authors: Romero Roberto , Miranda Jezid , Kusanovic Juan P. , Chaiworapongsa Tinnakorn , Chaemsaithong Piya , Martinez Alicia , Gotsch Francesca , Dong Zhong , Ahmed Ahmed I. , Shaman Majid , Lannaman Kia , Yoon Bo Hyun , Hassan Sonia S. , Kim Chong J. , Korzeniewski Steven J. , Yeo Lami , Kim Yeon Mee
Published: January 2015

The objectives of this study were: 1) to determine the amniotic fluid (AF) microbiology of patients with the diagnosis of clinical chorioamnionitis at term using both cultivation and molecular techniques; and 2) to examine the relationship between intra-amniotic inflammation with and without microorganisms and placental lesions consistent with acute AF infection.

The AF samples obtained by transabdominal amniocentesis from 46 women with clinical signs of chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anerobic bacteria as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation [defined as an AF interleukin 6 (IL-6) concentration ≥2.6 ng/mL], and placental lesions consistent with acute AF infection (acute histologic chorioamnionitis and/or acute funisitis) were examined according to the results of AF cultivation and PCR/ESI-MS as well as AF IL-6 concentrations.

1) Culture identified bacteria in AF from 46% (21/46) of the participants, whereas PCR/ESI-MS was positive for microorganisms in 59% (27/46) – combining these two tests, microorganisms were detected in 61% (28/46) of patients with clinical chorioamnionitis at term. Eight patients had discordant test results; one had a positive culture and negative PCR/ESI-MS result, whereas seven patients had positive PCR/ESI-MS results and negative cultures. 2)

Microorganisms in the AF were identified in 61% of patients with clinical chorioamnionitis at term; 54% had microbial-associated intra-amniotic inflammation, whereas 24% had intra-amniotic inflammation without detectable microorganisms.
Early and Persistent Abnormal Decoding by Glial Cells at the Neuromuscular Junction in an ALS Model
Authors: Arbour Danielle , Tremblay Elsa , Martineau Éric , Julien Jean-Pierre , Robitaille Richard
Published: January 2015

Amyotrophic lateral sclerosis (ALS) is a late-onset neuromuscular disease characterized by progressive loss of motor neurons (MNs) preceded by neuromuscular junction (NMJ) denervation. Despite the importance of NMJ denervation in ALS, the mechanisms involved remain unexplored and ill defined. The contribution of glial cells in the disease has been highlighted, including axonal Schwann cell activation that precedes the decline of motor function and the onset of hindlimb paralysis. Because NMJ denervation occurs early in the process and that perisynaptic Schwann cells (PSCs), glial cells at the NMJ, regulate morphological stability, integrity, and repair of the NMJ, one could predict that PSC functions would be altered even before denervation, contributing to NMJ malfunctions. We tested this possibility using a slowly progressive model of ALS (SOD1G37Rmice). We observed a normal NMJ organization at a presymptomatic stage of ALS (120 d), but PSC detection of endogenous synaptic activity revealed by intracellular Ca2+changes was enhanced compared with their wild-type littermates. This inappropriate PSC decoding ability was associated with an increased level of neurotransmitter release and dependent on intrinsic glial properties related to enhanced muscarinic receptor activation. The alteration of PSC muscarinic receptor functions also persists during the preonset stage of the disease and became dependent on MN vulnerability with age. Together, these results suggest that PSC properties are altered in the disease process in a manner that would be detrimental for NMJ repair. The impairments of PSC functions may contribute to NMJ dysfunction and ALS pathogenesis.
Leptin Receptor Signaling in the Hypothalamus Regulates Hepatic Autonomic Nerve Activity via Phosphatidylinositol 3-Kinase and AMP-Activated Protein Kinase
Authors: Tanida Mamoru , Yamamoto Naoki , Morgan Donald A. , Kurata Yasutaka , Shibamoto Toshishige , Rahmouni Kamal
Published: January 2015

Leptin action in the brain has emerged as an important regulator of liver function independently from its effects on food intake and body weight. The autonomic nervous system plays a key role in the regulation of physiological processes by leptin. Here, we used direct recording of nerve activity from sympathetic or vagal nerves subserving the liver to investigate how brain action of leptin controls hepatic autonomic nerve activity. Intracerebroventricular (ICV) administration of leptin activated hepatic sympathetic traffic in rats and mice in dose- and receptor-dependent manners. The hepatic sympatho-excitatory effects of leptin were also observed when leptin was microinjected directly into the arcuate nucleus (ARC), but not into the ventromedial hypothalamus (VMH). Moreover, using pharmacological and genetic approaches, we show that leptin-induced increase in hepatic sympathetic outflow depends on PI3K but not AMP-activated protein kinase (AMPK), STAT3, or ERK1/2. Interestingly, ICV leptin also increased hepatic vagal nerve activity in rats. We show that this response is reproduced by intra-ARC, but not intra-VMH, leptin administration and requires PI3K and AMPK. We conclude that central leptin signaling conveys the information to the liver through the sympathetic and parasympathetic branches of the autonomic nervous system. Our data also provide important insight into the molecular events underlying leptin's control of hepatic autonomic nerve activity by implicating PI3K and AMPK pathways.
DAMP Signaling is a Key Pathway Inducing Immune Modulation after Brain Injury
Authors: Liesz Arthur , Dalpke Alexander , Mracsko Eva , Roth Stefan , Zhou Wei , Yang Huan , Na Shin-Young , Akhisaroglu Mustafa , Fleming Thomas , Eigenbrod Tatjana , Nawroth Peter P. , Tracey Kevin J. , Veltkamp Roland
Published: January 2015

Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We investigated the inflammatory potency of HMGB1 and its signaling pathways by immunologicalin vivoandin vitrotechniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, was studied in various transgenic animal models and by pharmacological blockade. Our results indicate that HMGB1 was released from the ischemic brain in the hyperacute phase of stroke in mice and patients. Cytokines secreted in the periphery in response to brain injury induced sickness behavior, which could be abrogated by inhibition of the HMGB1-RAGE pathway or direct cytokine neutralization. Subsequently, HMGB1-release induced bone marrow egress and splenic proliferation of bone marrow-derived suppressor cells, inhibiting the adaptive immune responsesin vivoand vitro. Furthermore, HMGB1-RAGE signaling resulted in functional exhaustion of mature monocytes and lymphopenia, the hallmarks of immune suppression after extensive ischemia. This study introduces the HMGB1-RAGE-mediated pathway as a key mechanism explaining the complex postischemic brain-immune interactions.
Appraisal of Brain Connectivity in Radiologically Isolated Syndrome by Modeling Imaging Measures
Authors: Giorgio Antonio , Stromillo Maria Laura , De Leucio Alessandro , Rossi Francesca , Brandes Imke , Hakiki Bahia , Portaccio Emilio , Amato Maria Pia , De Stefano Nicola
Published: January 2015

We hypothesized that appraisal of brain connectivity may shed light on the substrate of the radiologically isolated syndrome (RIS), a term applied to asymptomatic subjects with brain MRI abnormalities highly suggestive of multiple sclerosis. We thus used a multimodal MRI approach on the human brain by modeling measures of microstructural integrity of white matter (WM) tracts with those of functional connectivity (FC) at the level of resting state networks in RIS subjects, demographically matched normal controls (NC), and relapsing-remitting (RR) MS patients, also matched with RIS for brain macrostructural damage (i.e., lesions and atrophy). Compared with NC, in both RIS subjects and MS patients altered integrity of WM tracts was present. However, RIS subjects showed, at a less conservative threshold, lower diffusivities than RRMS patients in distinct cerebral associative, commissural, projection, and cerebellar WM tracts, suggesting a relatively better anatomical connectivity. FC was similar in NC and RIS subjects, even in the presence of important risk factors for MS (spinal cord lesions, oligoclonal bands, and dissemination in time on MRI) and increased in RRMS patients in two clinically relevant networks subserving “processing” (sensorimotor) and “control” (working memory) functions. In RIS, the lack of functional reorganization in key brain networks may represent a model of “functional reserve,” which may become upregulated, with an adaptive or maladaptive role, only at a later stage in case of occurrence of clinical deficit.
Necessary, Yet Dissociable Contributions of the Insular and Ventromedial Prefrontal Cortices to Norm Adaptation: Computational and Lesion Evidence in Humans
Authors: Gu Xiaosi , Wang Xingchao , Hula Andreas , Wang Shiwei , Xu Shuai , Lohrenz Terry M. , Knight Robert T. , Gao Zhixian , Dayan Peter , Montague P. Read
Published: January 2015

Social norms and their enforcement are fundamental to human societies. The ability to detect deviations from norms and to adapt to norms in a changing environment is therefore important to individuals' normal social functioning. Previous neuroimaging studies have highlighted the involvement of the insular and ventromedial prefrontal (vmPFC) cortices in representing norms. However, the necessity and dissociability of their involvement remain unclear. Using model-based computational modeling and neuropsychological lesion approaches, we examined the contributions of the insula and vmPFC to norm adaptation in seven human patients with focal insula lesions and six patients with focal vmPFC lesions, in comparison with forty neurologically intact controls and six brain-damaged controls. There were three computational signals of interest as participants played a fairness game (ultimatum game): sensitivity to the fairness of offers, sensitivity to deviations from expected norms, and the speed at which people adapt to norms. Significant group differences were assessed using bootstrapping methods. Patients with insula lesions displayed abnormally low adaptation speed to norms, yet detected norm violations with greater sensitivity than controls. Patients with vmPFC lesions did not have such abnormalities, but displayed reduced sensitivity to fairness and were more likely to accept the most unfair offers. These findings provide compelling computational and lesion evidence supporting the necessary, yet dissociable roles of the insula and vmPFC in norm adaptation in humans: the insula is critical for learning to adapt when reality deviates from norm expectations, and that the vmPFC is important for valuation of fairness during social exchange.
Task-Induced Modulation of Intrinsic Functional Connectivity Networks in the Behaving Rat
Authors: Li Jennifer , Martin Sarah , Tricklebank Mark D. , Schwarz Adam J. , Gilmour Gary
Published: January 2015

While resting-state functional magnetic resonance imaging can probe intrinsic network connectivity in both human and rodent brain, behavioral modulation of these connectivity patterns has not yet been demonstrated in the rodent due to the requirements of immobilization or anesthesia for MRI scanning. To enable the effects of behavioral tasks on functional connectivity to be measured in freely moving, awake rats, implanted carbon paste electrodes (CPEs) were used to monitor low-frequency fluctuations of tissue oxygenation. Rats were implanted with CPEs in two nodes of the default mode network (DMN) and two nodes in a lateral cortical network, revealing amperometric oxygen correlation patterns consistent with imaging studies. Using a block design study where rats alternated between sustained periods of instrumental response and unscheduled spontaneous behavior, task-induced decreases in functional connectivity were observed between the DMN node pair, but not in the distinct lateral cortical network, demonstrating network-specific modulation of functional connectivity.
The Causal Role of the Occipital Face Area (OFA) and Lateral Occipital (LO) Cortex in Symmetry Perception
Authors: Bona Silvia , Cattaneo Zaira , Silvanto Juha
Published: January 2015

Symmetry is an important cue in face and object perception. Here we used fMRI-guided transcranial magnetic stimulation (TMS) to shed light on the role of the occipital face area (OFA), a key region in face processing, and the lateral occipital (LO) cortex, a key area in object processing, in symmetry detection. In the first experiment, we applied TMS over the rightOFA, its left homolog (leftOFA), rightLO, and vertex (baseline) while participants were discriminating between symmetric and asymmetric dot patterns. Stimulation of rightOFA and rightLO impaired performance, causally implicating these two regions in detection of symmetry in low-level dot configurations. TMS over rightLO but not rightOFA also significantly impaired detection of nonsymmetric shapes defined by collinear Gabor patches, demonstrating that rightOFA responds to symmetry but not to all cues mediating figure-ground segregation. The second experiment showed a causal role for rightOFA but not rightLO in facial symmetry detection. Overall, our results demonstrate that both the rightOFA and rightLO are sensitive to symmetry in dot patterns, whereas only rightOFA is causally involved in facial symmetry detection.
Distinguishing the Central Drive to Tremor in Parkinson's Disease and Essential Tremor
Authors: Brittain John-Stuart , Cagnan Hayriye , Mehta Arpan R. , Saifee Tabish A. , Edwards Mark J. , Brown Peter
Published: January 2015

Parkinson's disease (PD) and essential tremor (ET) are the two most common movement disorders. Both have been associated with similar patterns of network activation leading to the suggestion that they may result from similar network dysfunction, specifically involving the cerebellum. Here, we demonstrate that parkinsonian tremors and ETs result from distinct patterns of interactions between neural oscillators. These patterns are reflected in the tremors' derived frequency tolerance, a novel measure readily attainable from bedside accelerometry. Frequency tolerance characterizes the temporal evolution of tremor by quantifying the range of frequencies over which the tremor may be considered stable. We found that patients with PD (N= 24) and ET (N= 21) were separable based on their frequency tolerance, with PD associated with a broad range of stable frequencies whereas ET displayed characteristics consistent with a more finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by transcranial alternating current stimulation applied over cerebellum. Narrow frequency tolerances predicted stronger entrainment of tremor by stimulation, providing good evidence that the cerebellum plays an important role in pacing those tremors. The different patterns of frequency tolerance could be captured with a simple model based on a broadly coupled set of neural oscillators for PD, but a more finely tuned set of oscillators in ET. Together, these results reveal a potential organizational principle of the human motor system, whose disruption in PD and ET dictates how patients respond to empirical, and potentially therapeutic, interventions that interact with their underlying pathophysiology.
5α-Reduced Neurosteroids Sex-Dependently Reverse Central Prenatal Programming of Neuroendocrine Stress Responses in Rats
Authors: Brunton Paula J. , Donadio Marcio V. , Yao Song T. , Greenwood Mike , Seckl Jonathan R. , Murphy David , Russell John A.
Published: January 2015

Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA axis responses to a physical stressor (systemic interleukin-1β; IL-1β) in adulthood, compared with controls. IL-1β acts via a noradrenergic relay from the nucleus tractus solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone and 3β-androstanediol (3β-diol; 5α-reduced metabolites of progesterone and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to seek reversal of the “programmed” hyper-responsive HPA phenotype. Allopregnanolone attenuated ACTH responses to IL-1β (500 ng/kg, i.v.) in PNS females, but not in PNS males. However, 3β-diol normalized HPA axis responses to IL-1β in PNS males. Impaired testosterone and progesterone metabolism or increased secretion in PNS rats was indicated by greater plasma testosterone and progesterone concentrations in male and female PNS rats, respectively. Deficits in central neurosteroid production were indicated by reduced 5α-reductase mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in males. In PNS females, adenovirus-mediated gene transfer was used to upregulate expression of 5α-reductase and 3α-hydroxysteroid dehydrogenase mRNAs in the NTS, and this normalized hyperactive HPA axis responses to IL-1β. Thus, downregulation of neurosteroid production in the brain may underlie HPA axis hyper-responsiveness in prenatally programmed offspring, and administration of 5α-reduced steroids acutely to PNS rats overrides programming of hyperactive HPA axis responses to immune challenge in a sex-dependent manner.
Relationship between Nadir Hematocrit during Cardiopulmonary Bypass and Postoperative Hyperglycemia in Nondiabetic Patients
Authors: Sevuk Utkan , Cakil Nevzat , Altindag Rojhat , Baysal Erkan , Altintas Bernas , Yaylak Baris , Adiyaman Mehmet Sahin , Bahadir Mehmet Veysi
Published: January 2015

Background: Hyperglycemia is common after cardiac surgery in both diabetic and nondiabetic patients and is associated with increased morbidity and mortality. Association between nadir hematocrit levels on cardiopulmonary bypass (CPB) and postoperative hyperglycemia is not clear. This study was carried out to determine the relationship between nadir hematocrit during CPB and postoperative hyperglycemia in nondiabetic patients.

Methods: Records of 200 nondiabetic patients undergoing coronary artery bypass grafting operation were retrospectively reviewed. In the first analysis, patients were divided into two subgroups according to the presence or absence of hyperglycemia. Further analysis was made after dividing the patients into 3 subgroups according to nadir hematocrit levels on CPB (less than 20%; 20% to 25%; greater than or equal to 25%).

Results: Compared to patients without hyperglycemia, patients with postoperative hyperglycemia had significantly lower preoperative hematocrit levels (p = 0.004) and were associated with lower nadir hematocrit levels during CPB (p= 0.002). Peak intensive care unit blood glucose levels and number of blood transfusions were significantly higher in patients with nadir hematocrit levels less than 20. (p<0.001 and p<0.001 respectively). Logistic regression analysis demonstrated that nadir hematocrit levels less than 20% (OR 2.9, p=0.009) and allogenic blood transfusion (OR 1.5, p=0.003) were independently associated with postoperative hyperglycemia.

Conclusions: Nadir hematocrit levels on CPB less than 20% and allogenic blood transfusions were independently associated with postoperative hyperglycemia in nondiabetic patients. Patients with a nadir hematocrit levels less than 20 % during CPB should be closely monitored for hyperglycemia in the perioperative period.
Study of Mexican Colonial Mural Paintings: An In-situ Non-Invasive Approach
Authors: Ruvalcaba-Sil José Luis , Wong-Rueda Malinalli , Garcia-Bucio Maria Angelica , Casanova-Gonzalez Edgar , Manrique-Ortega Mayra Dafne , Aguilar-Melo Valentina , Claes Pieterjan , Aguilar-Tellez Dulce Maria
Published: January 2015

Colonial mural painting developed in Mexico in XVI century after the conquest of the pre-Hispanic cultures following the evangelization process little information exists about the chronology of the paintings and workshops, the painters, the pictorial techniques or the materiality of this art work.

In this work, we present the non-invasive methodology of study of the pigments and other components of nine mural paintings in three colonial Augustinian ex-convents located in Epazoyucan, Actopan and Ixmiquilpan, in the state of Hidalgo, central Mexico. These places were selected not only because of the inherent value and iconographic characteristics of the paintings, which date to the XVI and XVII century, but also because they are in the same region and are well preserved and in good condition. Then it is possible to compare their materiality and get new information to answer to some of questions related to these paintings.

X-ray Fluorescence (XRF) and Raman spectroscopy were conducted using portable equipment on scaffolds after a global examination under ultraviolet light. We were able to distinguish between different pigments used for different colors such as vermillion, orpiment, and a copper pigment, for the bright red, gold yellow, and green, respectively. These pigments are characteristic of the known Mexican Colonial color palette. Apart from this, we also found the presence of indigo in the blues, minium, and cochineal. A first comparison among the mural paintings of the three sites indicates different palettes and painting periods.
Adjuvant Therapy-Related Shortening of Survival (ATRESS): An Underrated Phenomenon
Authors: Fink Michael K. , Kleeberg Ulrich R. , Bartels Stefan
Published: January 2015

Shortening of survival after dissemination following adjuvant treatment is not understood well enough and is difficult to search for in public databases because of the lack of specific search terms. We suggest using the acronym ATRESS, for “adjuvant therapy-related shortening of survival,” in future literature concerning this issue.
Altitudinal assisted migration of Mexican pines as an adaptation to climate change
Authors: Castellanos-Acuña D. , Lindig-Cisneros R. , Sáenz-Romero C.
Published: January 2015

Since shifts in altitudinal range are expected in response to climate change, we explored the effect on survivorship and growth of moving populations of three Mexican pine species (Pinus devoniana, P. leiophyllaandP. pseudostrobus) to higher altitude, aiming to realign the populations to projected future climates in an experimental assisted migration. Twelve populations were collected across an altitudinal gradient (1650–2520 m above sea level [asl]) in a mountainous zone in the central‐west region of the Mexican Trans‐Volcanic Belt, and were planted in common garden tests at three forest sites of different altitudes (low: 2110, medium: 2422 and upper: 2746 m asl). Climate was estimated using a spline climatic model at the seed source and test sites and also measured using in situ data loggers. Survivorship and seedling height were evaluated in the field during the second and third growing seasons. Results were analyzed using mixed models to include the effect of climatic transfer distances (difference in climate between seed source and test site). Significant differences were found in seedling growth amongPinus devoniana,P. pseudostrobusandP. leiophylla, and among populations within the former two species. These were associated primarily with climatic transfer distances of extreme temperatures (minimum temperature in the coldest month and mean temperature in the warmest month). There was a significant decrease in growth inP. devonianawhen the transfer exceeded 650 m of upward altitudinal shift or a reduction of 1.5°C with transfer to colder sites. There was also a decrease of growth inP. pseudostrobuswhen transfer exceeded 400 m of upward altitudinal shift or 1.5°C, with a significant decrease in survivorship.Pinus leiophylla, however, exhibited similar growth at all altitudes tested, probably due to phenotypic plasticity. Although further research is required with field tests using commercial spacing and trees of older ages, the results suggest that an assisted upwards migration of 300 m in altitude, in order to approach a realignment of the populations to the climate projected for the decade centered around the year 2030, appears to be a viable strategy with which to accommodate the effects of climate change.
Design and Operating Features of the SEDCO 135-F Floating Drilling Vessel
Authors: Pounds W.G. , Zaruby W.S.
Published: January 2015

This paper describes the design of one of the largest semi-submersible drilling vessels ever constructed. The arrangement and operating features of the drilling machinery and auxiliary underwater drilling equipment are also reviewed. The SEDCO 135-F is presently under construction at Victoria Machinery Depot in Victoria, B.C. Sister vessels have been completed and are in operation in the Gulf of Mexico, off Borneo, in the North Sea and off Nigeria.

The physical layout of the vessel is presented in terms of its unusual shape, size and arrangement of equipment and accommodations. The diesel-electric power plant provides D.C. power for the heavy machinery and A.C. power for miscellaneous ship service. Electrically driven deep-well pumps are used to deballast the vessel and to move water and fuel from the lower compartments to the operating deck level. Other mechanical features include three large cranes, pneumatic storage tanks and other special equipment required to handle the underwater drilling equipment.

Due to the severe oceanographic conditions off the west coast of Canada, a special mooring system was designed to secure the rig under adverse conditions. The design criteria, hardware and operation of this system are reviewed.

The vessel will be equipped with specialized underwater equipment to enable it to drill exploratory wells in water depths of up to 800 feet. The hydraulically operated well control equipment is situated on the ocean floor during normal operations. This "diverless" equipment is described, along with its handling and operating procedures.
The Relationship of the Westerose D-3 Pool to Other Pools on the Common Aquifer
Authors: Hnatiuk John , Martinelli J.W.
Published: January 2015

A study of a 70-mile chain of prolific Leduc D-3 reef pools situated on a common aquifer is presented. The primary objective of the study was the prediction of the future performance of the centrally located Westerose D-3 Pool, as influenced by other pools in the trend. A two-dimensional mathematical model of the Acheson-Homeglen Rimbey Leduc D-3 reef chain was developed. Values of resistance and capacitance, characterizing reservoir parameters, were assigned to the grid points in the reservoir simulator. These were adjusted until a satisfactory match with twenty years of performance history was obtained. The future pressure performance and water influx or efflux under many combinations of producing rates were predicted for a ten-year period. The study indicated unusual trends in pressure and water influx behaviour resulting from interference effects. Further movement of Westerose oil into the underlying aquifer was predicted with continued injection of produced solution gas. These results were instrumental in the recent termination of gas injection into the Westerose D-3 Pool. The study also predicted the withdrawal rates necessary from the Westerose D-3 Pool to maintain the oil-water interface at its current position and to control its further movement.
Carbonate Scale Formation on Steel Surfaces
Authors: Diebes E.F. , Jessen F.W.
Published: January 2015

This study was concerned with scale deposition on heated steel disks under controlled laboratory conditions. Produced brines from fields in South and West Texas were used as the scaling solutions. These brines exhibited a wide range of salt concentration. A laboratory testing apparatus was developed. The main feature of the new apparatus is its ability to measure the skin temperature (i.e., the temperature at the brine-steel interface). A series of tests were made covering a temperature range of from 120 to 190°F. This temperature range represents a variety of field conditions, from surface to downhole. A quantitative measurement of calcium carbonate deposition vs temperature was obtained. Thirteen selected chemicals were tested for possible use as scale inhibitors. The selection was based on the properties that might affect scale deposition, such as dispersion, sequestration, interionic action, film formation ... etc. The inhibition of scale by the various chemicals used was found to vary considerably. Film-forming compounds in the presence of crude oil proved highly effective. The nature of the scale crystals and the influence of the additives on crystal habit modification was studied through microscopic examination and photomicrographs. X-ray studies were used to indicate the chemical nature of the scale. The experimental procedure and conditions under which scale is deposited were found to be of great importance. In view of the encouraging results, the field application of film-forming compounds as scale inhibitors is highly recommended.
A Computer-Oriented Method of Pressure Build-Up Analysis
Authors: Knutson G.C.
Published: January 2015

A method of estimating reservoir pressure from pressure build-up information has been developed which utilizes a mathematical analysis of the measured pressures to determine that portion of the pressure build-up history to be employed in the bottom-hole pressure extrapolation. The reservoir pressure is then determined by a linear regression analysis of those data to be included. As only the shut-in time and the measured pressures are required, the results do not depend on correct estimates of additional reservoir factors. The method does, however, yield information on the basis of which estimates of reservoir transmissibility can be made. The method can best be employed utilizing a digital computer because of the large number of calculations required. The technique is particularly useful in the routine analysis of pressure build-up information, because the calculations can be carried out with a minimum of engineering time.