bluuebunny/crossref_metadata_2025 huggingface dataset:
How I treat patients with massive hemorrhage
Authors: Johansson Pär I. , Stensballe Jakob , Oliveri Roberto , Wade Charles E. , Ostrowski Sisse R. , Holcomb John B.
Published: October 2014

Massive hemorrhage is associated with coagulopathy and high mortality. The transfusion guidelines up to 2006 recommended that resuscitation of massive hemorrhage should occur in successive steps using crystalloids, colloids, and red blood cells (RBCs) in the early phase and plasma and platelets in the late phase. With the introduction of the cell-based model of hemostasis in the mid-1990s, our understanding of the hemostatic process and of coagulopathy has improved. This has contributed to a change in resuscitation strategy and transfusion therapy of massive hemorrhage along with an acceptance of the adequacy of whole blood hemostatic tests to monitor these patients. Thus, in 2005, a strategy aiming at avoiding coagulopathy by proactive resuscitation with blood products in a balanced ratio of RBC:plasma:platelets was introduced, and this has been reported to be associated with reduced mortality in observational studies. Concurrently, whole blood viscoelastic hemostatic assays have gained acceptance by allowing a rapid and timely identification of coagulopathy along with enabling an individualized, goal-directed transfusion therapy. These strategies joined together seem beneficial for patient outcome, although final evidence on outcome from randomized controlled trials are lacking. We present how we in Copenhagen and Houston, today, manage patients with massive hemorrhage.
CD4+ invariant natural killer T cells protect from murine GVHD lethality through expansion of donor CD4+CD25+FoxP3+ regulatory T cells
Authors: Schneidawind Dominik , Pierini Antonio , Alvarez Maite , Pan Yuqiong , Baker Jeanette , Buechele Corina , Luong Richard H. , Meyer Everett H. , Negrin Robert S.
Published: October 2014

Key Points

Low doses of adoptively transferred donor CD4+ iNKT cells protect from GVHD while preserving graft-versus-tumor effects. Donor CD4+ iNKT cells inhibit proliferation of alloreactive T cells and promote robust expansion of donor Tregs.
Brentuximab vedotin
Authors: Ansell Stephen M.
Published: October 2014

Brentuximab vedotin is an anti-CD30 antibody-drug conjugate with proven efficacy in patients with CD30+ malignancies, including classical Hodgkin lymphoma and anaplastic large cell lymphoma. Promising activity has also been seen in other lymphomas that express CD30. Because of its acceptable toxicity profile and significant clinical efficacy, single-agent brentuximab vedotin is an approved treatment for relapsed patients with these diseases. Brentuximab vedotin has safely been combined with chemotherapy and is now being compared with standard treatments in randomized trials.
Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients
Authors: Khellaf Mehdi , Charles-Nelson Anaïs , Fain Olivier , Terriou Louis , Viallard Jean-François , Cheze Stéphane , Graveleau Julie , Slama Borhane , Audia Sylvain , Ebbo Mikael , Le Guenno Guillaume , Cliquennois Manuel , Salles Gilles , Bonmati Caroline , Teillet France , Galicier Lionel , Hot Arnaud , Lambotte Olivier , Lefrère François , Sacko Salimatou , Kengue Dieudonné Kilendo , Bierling Philippe , Roudot-Thoraval Françoise , Michel Marc , Godeau Bertrand
Published: October 2014

Key Points

Tolerance of rituximab is acceptable in ITP, and with its benefit/risk ratio may remain a valid option for treating ITP in adults.
Prevalence of active foot disease and foot disease risk factors in a subacute inpatient rehabilitation facility: a cross‐sectional prevalence study
Authors: Earl Brenton J , Lazzarini Peter A , Kinnear Ewan M , Cornwell Petrea L
Published: October 2014

Background

Australian subacute inpatient rehabilitation facilities face significant challenges from the ageing population and the increasing burden of chronic disease. Foot disease complications are a negative consequence of many chronic diseases. With the rapid expansion of subacute rehabilitation inpatient services, it seems imperative to investigate the prevalence of foot disease and foot disease risk factors in this population. The primary aim of this cross‐sectional study was to determine the prevalence of active foot disease and foot disease risk factors in a subacute inpatient rehabilitation facility.

Methods

Eligible participants were all adults admitted at least overnight into a large Australian subacute inpatient rehabilitation facility over two different four week periods. Consenting participants underwent a short non‐invasive foot examination by a podiatrist utilising the validated Queensland Health High Risk Foot Form to collect data on age, sex, medical co‐morbidity history, foot disease risk factor history and clinically diagnosed foot disease complications and foot disease risk factors. Descriptive statistics were used to determine the prevalence of clinically diagnosed foot disease complications, foot disease risk factors and groups of foot disease risk factors. Logistic regression analyses were used to investigate any associations between defined explanatory variables and appropriate foot disease outcome variables.

Results

Overall, 85 (88%) of 97 people admitted to the facility during the study periods consented; mean age 80 (±9) years and 71% were female. The prevalence (95% confidence interval) of participants with active foot disease was 11.8% (6.3 – 20.5), 32.9% (23.9 – 43.5) had multiple foot disease risk factors, and overall, 56.5% (45.9 – 66.5) had at least one foot disease risk factor. A self‐reported history of peripheral neuropathy diagnosis was independently associated with having multiple foot disease risk factors (OR 13.504, p = 0.001).

Conclusion

This study highlights the potential significance of the burden of foot disease in subacute inpatient rehabilitation facilities. One in eight subacute inpatients were admitted with active foot disease and one in two with at least one foot disease risk factor in this study. It is recommended that further multi‐site studies and management guidelines are required to address the foot disease burden in subacute inpatient rehabilitation facilities.
Decentralized group formation
Authors: Chmielowiec Anna , Voulgaris Spyros , Steen Maarten van
Published: October 2014

Imagine a network of entities, being it replica servers aiming to minimize the probability of data loss, players of online team-based games and tournaments, or companies that look into co-branding opportunities. The objective of each entity in any of these scenarios is to find a few suitable partners to help them achieve a shared goal: replication of the data for fault tolerance, winning the game, successful marketing campaign. All information attainable by the entities is limited to the profiles of other entities that can be used to assess the pairwise fitness. How can they create teams without help of any centralized component and without going into each other’s way? We propose a decentralized algorithm that helps nodes in the network to form groups of a specific size. The protocol works by finding an approximation of a weighted k-clique matching of the underlying graph of assessments. We discuss the basic version of the protocol, and explain how dissemination via gossiping helps in improving its scalability. We evaluate its performance through extensive simulations.
Analysis of microsatellites in the vulnerable orchid Gastrodia flavilabella: the development of microsatellite markers, and cross-species amplification in Gastrodia
Authors: Tsai Chi-Chu , Wu Pei-Yin , Kuo Chia-Chi , Huang Min-Chun , Yu Sheng-Kun , Hsu Tsai-Wen , Chiang Tzen-Yuh , Chiang Yu-Chung
Published: October 2014

Background

Gastrodia flabilabella is a mycoheterotrophic orchid that obtains carbohydrates and nutrients from its symbiotic mycorrhizal fungi. The species is an endemic and vulnerable species enlisted in the “A Preliminary Red List of Taiwanese Vascular Plants” according to the IUCN Red List Categories and Criteria Version 3.1. G. flabilabella dwells the underground of broadleaf and coniferous forest with richness litter. Based on herbarium records, this species is distributed in central Taiwan. Twenty eight microsatellite loci were developed in G. flabilabella and were tested for cross-species amplification in additional taxa of G. confusoides, G. elata, and G. javanica. We estimated the genetic variation that is valuable for conservation management and the development of the molecular identification system for G. elata, a traditional Chinese medicine herb.

Results

Microsatellite primer sets were developed from G. flabilabella using the modified AFLP and magnetic bead enrichment method. In total, 257 microsatellite loci were obtained from a magnetic bead enrichment SSR library. Of the 28 microsatellite loci, 16 were polymorphic, in which the number of alleles ranged from 2 to 15, with the observed heterozygosity ranging from 0.02 to 1.00. In total, 15, 13, and 7 of the loci were found to be interspecifically amplifiable to G. confusoides, G. elata, and G. javanica, respectively.

Conclusions

Amplifiable and transferable microsatellite loci are potentially useful for future studies in investigating intraspecific genetic variation, reconstructing phylogeographic patterns among closely related species, and establishing the standard operating system of molecular identification in Gastrodia.
Use of a National Continuing Medical Education Meeting to Provide Simulation-Based Training in Temporary Hemodialysis Catheter Insertion Skills: A Pre-Test Post-Test Study
Authors: Clark Edward G , Paparello James J , Wayne Diane B , Edwards Cedric , Hoar Stephanie , McQuillan Rory , Schachter Michael E , Barsuk Jeffrey H
Published: October 2014

Background:

Simulation-based-mastery-learning (SBML) is an effective method to train nephrology fellows to competently insert temporary, non-tunneled hemodialysis catheters (NTHCs). Previous studies of SBML for NTHC-insertion have been conducted at a local level.

Objectives:

Determine if SBML for NTHC-insertion can be effective when provided at a national continuing medical education (CME) meeting. Describe the correlation of demographic factors, prior experience with NTHC-insertion and procedural self-confidence with simulated performance of the procedure.

Design:

Pre-test – post-test study.

Setting:

2014 Canadian Society of Nephrology annual meeting.

Participants:

Nephrology fellows, internal medicine residents and medical students.

Measurements:

Participants were surveyed regarding demographics, prior NTHC-insertion experience, procedural self-confidence and attitudes regarding the training they received. NTHC-insertion skills were assessed using a 28-item checklist.

Methods:

Participants underwent a pre-test of their NTHC-insertion skills at the internal jugular site using a realistic patient simulator and ultrasound machine. Participants then had a training session that included a didactic presentation and 2 hours of deliberate practice using the simulator. On the following day, trainees completed a post-test of their NTHC-insertion skills. All participants were required to meet or exceed a minimum passing score (MPS) previously set at 79%. Trainees who did not reach the MPS were required to perform more deliberate practice until the MPS was achieved.

Results:

Twenty-two individuals participated in SBML training. None met or exceeded the MPS at baseline with a median checklist score of 20 (IQR, 7.25 to 21). Seventeen of 22 participants (77%) completed post-testing and improved their scores to a median of 27 (IQR, 26 to 28; p < 0.001). All met or exceeded the MPS on their first attempt. There were no significant correlations between demographics, prior experience or procedural self-confidence with pre-test performance.

Limitations:

Small sample-size and self-selection of participants. Costs could limit the long-term feasibility of providing this type of training at a CME conference.

Conclusions:

Despite most participants reporting having previously inserted NTHCs in clinical practice, none met the MPS at baseline; this suggests their prior training may have been inadequate.
Monetary Policy without Interest Rates: Evidence from France’s Golden Age (1948 to 1973) Using a Narrative Approach
Authors: Monnet Eric
Published: October 2014

Central banking in France from 1948 to 1973 was a paradigmatic example of a policy that relied on quantities rather than interest rates. Standard SVAR analyses support the common view that monetary policy was ineffective during this period. However, this approach fails to identify the stance of monetary policy since it does not account for the specificity of quantitative controls on money and credit. An alternative identification strategy based on a narrative approach suggests that monetary policy shocks had strong and lasting effects in the conventional direction and accounted for nearly half of the variance in output and price levels. (JEL E43, E44, E52, E58, G21, G28, N14)
The Political Economy of the Greek Debt Crisis: A Tale of Two Bailouts
Authors: Ardagna Silvia , Caselli Francesco
Published: October 2014

We review the events that led to the May 2010 and July 2011 bailout agreements. We interpret the bailouts as outcomes of political-economy equilibria. We argue that these equilibria were likely not on the Pareto frontier, and sketch political-economy arguments for why collective policymaking in the Euro area may lead to suboptimal outcomes. (JEL E58, E62, F34, G01, H61, H63)
Numerical Simulation of Failure of Anchorage with Shifted Mechanical Anchorage Bars by 3D Discrete Model
Authors: Nagai K. , Hayashi D. , Eddy L.
Published: October 2014

Nowadays, seismic design code in Japan is becoming more stringent. To satisfy the strict requirement, larger numbers of reinforcements must be placed, resulting in increased reinforcement congestion. To reduce the reinforcement congestion, mechanical anchorage is becoming popular in use instead of conventional hook rebar. However the behavior of mechanical anchorage placed in thin cover zone is not well understood, and the use of this is still limited. In this study, the discrete element method was used to investigate the performance of mechanical anchorage placed in thin cover depth zone, and the pull-out test in previous research was simulated. To assume that anchor plates welded to bar end are difficult to place side by side due to closely-spaced reinforcements, the position of anchor plate was taken as main parameter. The result shows that the anchorage performance changed according to the transverse bars effect and the shift of the mechanical anchorage. The simulations show good agreement with experiment data in terms of the anchorage capacity, crack pattern and failure mode.
Performance of Recycled Aggregate Concrete in a Real Project
Authors: Zhang Hongru , Zhao Yuxi
Published: October 2014

Though a large amount of research has been carried out on recycled aggregate concrete (RAC) during recent years, the application cases of RAC in real structures are still very few in China. This paper reports the application of RAC in a real project. Two beams made of RAC and commercial natural aggregate concrete (NAC) respectively were cast in-situ to carry out the tests. The two beams were subjected to the similar service loading, so that the performance of the RAC beam could be compared with that of the NAC one. Compressive strength, degree of density and uniformity were tested for both types of concrete at representative ages, and concrete strain of the two target beams was monitored regularly from the age from 1 d to 420 d. The results from laboratory tests and on-site monitoring have proved the feasibility and reliability of the application of RAC in real structures though RAC is generally inferior to NAC.
Dehydrated human amnion/chorion membrane for the treatment of severe skin and tissue loss in an preterm infant: a case report
Authors: Tenenhaus M. , Greenberg M. , Potenza B.
Published: October 2014

Extreme prematurity complicated with severe congenital cutaneous candidiasis (CCC) is rare and clinically challenging. We present the case of a 615g dizygotic twin delivered at 24 weeks gestation with congenital candidiasis, who developed severe skin and tissue loss, successfully treated with dehydrated human amnion/chorion membrane (dHACM). The infant had a complicated medical course, including treatment for patent ductus arteriosus (PDA), necrotising enterocolitis (NEC), and neonatal abstinence syndrome (NAS). In the operating room after debridement, dHACM was placed over all abdominal and back areas of skin loss and covered with a non-occlusive, non-adherent silver dressing. This dressing regimen was chosen in an effort to provide not only topical antimicrobial coverage, but also to maintain a non-shear, moist wound healing environment, which was so important in the dry incubator environment of the neonatal intensive care centre. Over the next four weeks, the baby was medically managed, and the wounds healed on their own with only weekly bedside dressing changes. This case report provides the first example of successful complex management of extensive life-threatening wounds in a premature infant using dHACM.
Government policies for corporate social responsibility in Europe: a comparative analysis of institutionalisation
Authors: Knudsen Jette Steen , Moon Jeremy , Slager Rieneke
Published: October 2014

This paper analyses policies of 22 European Union member governments, designed to encourage corporate social responsibility (CSR) between 2000 and 2011. It categorises these policies by their regulatory strength and identifies the range of issues to which CSR policies are directed. The paper argues that Northern European, Scandinavian and UK governments are reconstructing their respective institutional structures to embed CSR concerns more explicitly therein. It concludes that these government CSR initiatives are converging, particularly around their increased regulatory strength and the broadening of their issue application. Policies in Mediterranean and the former communist countries do not reflect increasing institutionalisation.
Single-Tube, Highly Parallel Mutation Enrichment in Cancer Gene Panels by Use of Temperature-Tolerant COLD-PCR
Authors: Castellanos-Rizaldos Elena , Richardson Katherine , Lin Rui , Wu Grant , Makrigiorgos Mike G
Published: October 2014

BACKGROUND

Multiplexed detection of low-level mutations presents a technical challenge for many technologies, including cancer gene panels used for targeted-resequencing. Analysis of mutations below approximately 2%–5% abundance in tumors with heterogeneity, samples with stromal contamination, or biofluids is problematic owing to increased noise from sequencing errors. Technologies that reduce noise via deep sequencing unavoidably reduce throughput and increase cost. Here we provide proof of principle that coamplification at lower denaturation temperature (COLD)-PCR technology enables multiplex low-level mutation detection in cancer gene panels while retaining throughput.

METHODS

We have developed a multiplex temperature-tolerant COLD-PCR (fast-TT-COLD-PCR) approach that uses cancer gene panels developed for massively parallel sequencing. After multiplex preamplification from genomic DNA, we attach tails to all amplicons and perform fast-TT-COLD-PCR. This approach gradually increases denaturation temperatures in a step-wise fashion, such that all possible denaturation temperatures are encompassed. By introducing modified nucleotides, fast-COLD-PCR is adapted to enrich for melting temperature (Tm)-increasing mutations over all amplicons, in a single tube. Therefore, in separate reactions, both Tm-decreasing and Tm-increasing mutations are enriched.

RESULTS

Using custom-made and commercial gene panels containing 8, 50, 190, or 16 000 amplicons, we demonstrate that fast-TT-COLD-PCR enriches mutations on all examined targets simultaneously. Incorporation of deoxyinosine triphosphate (dITP)/2,6-diaminopurine triphosphate (dDTP) in place of deoxyguanosine triphosphate (dGTP)/deoxyadenosine triphosphate (dATP) enables enrichment of Tm-increasing mutations. Serial dilution experiments demonstrate a limit of detection of approximately 0.01%–0.1% mutation abundance by use of Ion-Torrent and 0.1%–0.3% by use of Sanger sequencing.

CONCLUSIONS

Fast-TT-COLD-PCR improves the limit of detection of cancer gene panels by enabling mutation enrichment in multiplex, single-tube reactions. This novel adaptation of COLD-PCR converts subclonal mutations to clonal, thereby facilitating detection and subsequent mutation sequencing.
Patron Driven Acquisition – eine Herausforderung (auch) für Verbundzentralen
Authors: Albrecht Rita
Published: October 2014

Das noch relativ junge Modell „Patron Driven Acquisition“ wird inzwischen von vielen Bibliotheken für die Erwerbung von E-Books praktiziert. Dabei wird nach einem bibliothekseigenen Profil eine Sammlung von E-Books (manchmal auch Printtitel) durch einen Anbieter zur Nutzung bereitgestellt, ein Kauf aber erst durch die Anforderung des Dokuments durch einen Bibliotheksbenutzer ausgelöst, wofür es verschiedene Modelle und Modalitäten je nach Anbieter gibt. Verbundbibliotheken erwarten von ihren Verbundzentralen auch für diese Erwerbungsform ein schnelles, umfassendes Metadatenhandling und stellen sie damit vor neue Herausforderungen. Der folgende Beitrag beschreibt exemplarisch die Metadatenpraxis im HeBIS-Verbund.
On sarcasm, social awareness, and gender
Authors: Drucker Ari , Fein Ofer , Bergerbest Dafna , Giora Rachel
Published: October 2014

Sarcastic irony, uttered in four (within and between) gender-based settings, is used here as a tool to diagnose affective attitudes toward women. The kind of sarcasm tested here is an aggressive type of humor, whereby a speaker derides another individual, turning her or him into the victim of the humorous utterance. Finding this kind of irony less or more pleasing allows indexing between- and within-group attitudes. Participants were overall nonsexist, scoring low on sexism scales, but male participants were still more sexist than female participants. Results show that, as predicted by Ariel and Giora (1998), female participants fully adopted a feminine point of view, enjoying sarcastic irony best when it was directed by women at men and least when it was directed by women at women. Being more sexist, our male participants adopted a feminine point of view only partially, enjoying sarcastic irony more when directed at men than directed at women, regardless of the speaker's gender.
A relevance-theoretic perspective on humorous irony and its failure
Authors: Piskorska Agnieszka
Published: October 2014

This paper adopts the relevance-theoretic account of irony to describe the features of humorous irony and to elucidate the nuances of its failure. In connection to the humorous potential of irony, a number of properties it shares with some types of humor are discussed, such as exploiting incongruity, being targeted at a victim, being creative, carrying an element of surprise, involving metarepresentational abilities, and establishing a bond between the speaker and hearer. It is further observed that ironic utterances produced for the purpose of generating humor and increasing rapport between interlocutors may fail to achieve this aim to various degrees and due to a number of causes. Analyses of several examples indicate that the various causes of ironic misfires can be traced to failures of the inferential processes postulated by Relevance Theory as responsible for communicating irony: identifying a dissociative propositional attitude, representing the content of the proposition echoed, and attributing it to a source. Besides, it is claimed that humorous irony is used not only to communicate an attitude but also to have it accepted by the hearer, which is why the latter's rejection of the speaker-envisaged ironic attitude counts as another type of irony failure.
Non-immune hydrops fetalis as a diagnostic and survival problems: what do we tell the parents?
Authors: Turgal Mert , Ozyuncu Ozgur , Boyraz Gokhan , Yazicioglu Aslihan , Sinan Beksac Mehmet
Published: October 2014

Objective: Nonimmune hydrops fetalis (NIHF) is one of the most difficult problems related to pregnancy. The aim of this study was to evaluate the etiological analysis as well as the fetal and neonatal outcomes of NIHF.

Methods: We reviewed the prenatal sonographic data and postnatal medical records of pregnant women diagnosed as NIHF in our hospital between January 2001 and May 2013. All cases were categorized using 12 etiological classification groups. Demographic data, diagnostic laboratory parameters, karyotyping results, sonographic and autopsy findings, postnatal final diagnoses, and perinatal mortality rates were also recorded.

Results: This study included 147 cases. The mean gestational age at the time of the initial diagnosis was 23.84±6.30 weeks. Cardiovascular causes were the most common (21.7%), followed by structural abnormalities (17.0%), chromosomal abnormalities (6.8%), and skeletal dysplasias (5.4%). Chromosomal abnormalities were detected in 12.8% of these cases. The most common karyotype abnormality was monosomy X. Postmortem autopsy was performed in 50 (34%) cases, and at least one finding was detected in 40 (80%) of these cases. The overall mortality rate was 78.2%. The gestational week at delivery, birth weight, and Apgar score (1st and 5th min) showed a statistically significant difference between exitus and surviving fetuses (P<0.05).

Conclusion: NIHF can lead to high perinatal morbidity and mortality, yet its etiopathology remains poorly understood. Early diagnosis of NIHF gives parents an opportunity to make an informed choice about the possible complications of a pregnancy.
The Schizophrenia Susceptibility GeneDysbindinRegulates Dendritic Spine Dynamics
Authors: Jia Jie-Min , Hu Zhonghua , Nordman Jacob , Li Zheng
Published: October 2014

Dysbindinis a schizophrenia susceptibility gene required for the development of dendritic spines. The expression of dysbindin proteins is decreased in the brains of schizophrenia patients, and neurons in mice carrying a deletion in thedysbindingene have fewer dendritic spines. Hence, dysbindin might contribute to the spine pathology of schizophrenia, which manifests as a decrease in the number of dendritic spines. The development of dendritic spines is a dynamic process involving formation, retraction, and transformation of dendritic protrusions. It has yet to be determined whether dysbindin regulates the dynamics of dendritic protrusions. Here we address this question using time-lapse imaging in hippocampal neurons. Our results show that dysbindin is required to stabilize dendritic protrusions. In dysbindin-null neurons, dendritic protrusions are hyperactive in formation, retraction, and conversion between different types of protrusions. We further show that CaMKIIα is required for the stabilization of mushroom/thin spines, and that the hyperactivity of dendritic protrusions in dysbindin-null neurons is attributed in part to decreased CaMKIIα activity resulting from increased inhibition of CaMKIIα by Abi1. These findings elucidate the function of dysbindin in the dynamic morphogenesis of dendritic protrusions, and reveal the essential roles of dysbindin and CaMKIIα in the stabilization of dendritic protrusions during neuronal development.
Spontaneous Microsaccades Reflect Shifts in Covert Attention
Authors: Yuval-Greenberg Shlomit , Merriam Elisha P. , Heeger David J.
Published: October 2014

Microsaccade rate during fixation is modulated by the presentation of a visual stimulus. When the stimulus is an endogenous attention cue, the ensuing microsaccades tend to be directed toward the cue. This finding has been taken as evidence that microsaccades index the locus of spatial attention. But the vast majority of microsaccades that subjects make are not triggered by visual stimuli. Under natural viewing conditions, spontaneous microsaccades occur frequently (2–3 Hz), even in the absence of a stimulus or a task. While spontaneous microsaccades may depend on low-level visual demands, such as retinal fatigue, image fading, or fixation shifts, it is unknown whether their occurrence corresponds to changes in the attentional state. We developed a protocol to measure whether spontaneous microsaccades reflect shifts in spatial attention. Human subjects fixated a cross while microsaccades were detected from streaming eye-position data. Detection of a microsaccade triggered the appearance of a peripheral ring of grating patches, which were followed by an arrow (a postcue) indicating one of them as the target. The target was either congruent or incongruent (opposite) with respect to the direction of the microsaccade (which preceded the stimulus). Subjects reported the tilt of the target (clockwise or counterclockwise relative to vertical). We found that accuracy was higher for congruent than for incongruent trials. We conclude that the direction of spontaneous microsaccades is inherently linked to shifts in spatial attention.
Working Memory Contributions to Reinforcement Learning Impairments in Schizophrenia
Authors: Collins Anne G.E. , Brown Jaime K. , Gold James M. , Waltz James A. , Frank Michael J.
Published: October 2014

Previous research has shown that patients with schizophrenia are impaired in reinforcement learning tasks. However, behavioral learning curves in such tasks originate from the interaction of multiple neural processes, including the basal ganglia- and dopamine-dependent reinforcement learning (RL) system, but also prefrontal cortex-dependent cognitive strategies involving working memory (WM). Thus, it is unclear which specific system induces impairments in schizophrenia. We recently developed a task and computational model allowing us to separately assess the roles of RL (slow, cumulative learning) mechanisms versus WM (fast but capacity-limited) mechanisms in healthy adult human subjects. Here, we used this task to assess patients' specific sources of impairments in learning. In 15 separate blocks, subjects learned to pick one of three actions for stimuli. The number of stimuli to learn in each block varied from two to six, allowing us to separate influences of capacity-limited WM from the incremental RL system. As expected, both patients (n= 49) and healthy controls (n= 36) showed effects of set size and delay between stimulus repetitions, confirming the presence of working memory effects. Patients performed significantly worse than controls overall, but computational model fits and behavioral analyses indicate that these deficits could be entirely accounted for by changes in WM parameters (capacity and reliability), whereas RL processes were spared. These results suggest that the working memory system contributes strongly to learning impairments in schizophrenia.
Alzheimer's Disease-Like Pathology Induced by Amyloid-β Oligomers in Nonhuman Primates
Authors: Forny-Germano Leticia , Lyra e Silva Natalia M. , Batista André F. , Brito-Moreira Jordano , Gralle Matthias , Boehnke Susan E. , Coe Brian C. , Lablans Ann , Marques Suelen A. , Martinez Ana Maria B. , Klein William L. , Houzel Jean-Christophe , Ferreira Sergio T. , Munoz Douglas P. , De Felice Fernanda G.
Published: October 2014

Alzheimer's disease (AD) is a devastating neurodegenerative disorder and a major medical problem. Here, we have investigated the impact of amyloid-β (Aβ) oligomers, AD-related neurotoxins, in the brains of rats and adult nonhuman primates (cynomolgus macaques). Soluble Aβ oligomers are known to accumulate in the brains of AD patients and correlate with disease-associated cognitive dysfunction. When injected into the lateral ventricle of rats and macaques, Aβ oligomers diffused into the brain and accumulated in several regions associated with memory and cognitive functions. Cardinal features of AD pathology, including synapse loss, tau hyperphosphorylation, astrocyte and microglial activation, were observed in regions of the macaque brain where Aβ oligomers were abundantly detected. Most importantly, oligomer injections induced AD-type neurofibrillary tangle formation in the macaque brain. These outcomes were specifically associated with Aβ oligomers, as fibrillar amyloid deposits were not detected in oligomer-injected brains. Human and macaque brains share significant similarities in terms of overall architecture and functional networks. Thus, generation of a macaque model of AD that links Aβ oligomers to tau and synaptic pathology has the potential to greatly advance our understanding of mechanisms centrally implicated in AD pathogenesis. Furthermore, development of disease-modifying therapeutics for AD has been hampered by the difficulty in translating therapies that work in rodents to humans. This new approach may be a highly relevant nonhuman primate model for testing therapeutic interventions for AD.
A Feedforward Inhibitory Circuit Mediates Lateral Refinement of Sensory Representation in Upper Layer 2/3 of Mouse Primary Auditory Cortex
Authors: Li Ling-yun , Ji Xu-ying , Liang Feixue , Li Ya-tang , Xiao Zhongju , Tao Huizhong W. , Zhang Li I.
Published: October 2014

Sensory information undergoes ordered and coordinated processing across cortical layers. Whereas cortical layer (L) 4 faithfully acquires thalamic information, the superficial layers appear well staged for more refined processing of L4-relayed signals to generate corticocortical outputs. However, the specific role of superficial layer processing and how it is specified by local synaptic circuits remains not well understood. Here, in the mouse primary auditory cortex, we showed that upper L2/3 circuits play a crucial role in refining functional selectivity of excitatory neurons by sharpening auditory tonal receptive fields and enhancing contrast of frequency representation. This refinement is mediated by synaptic inhibition being more broadly recruited than excitation, with the inhibition predominantly originating from interneurons in the same cortical layer. By comparing the onsets of synaptic inputs as well as of spiking responses of different types of neuron, we found that the broadly tuned, fast responding inhibition observed in excitatory cells can be primarily attributed to feedforward inhibition originating from parvalbumin (PV)-positive neurons, whereas somatostatin (SOM)-positive interneurons respond much later compared with the onset of inhibitory inputs to excitatory neurons. We propose that the feedforward circuit-mediated inhibition from PV neurons, which has an analogous function to lateral inhibition, enables upper L2/3 excitatory neurons to rapidly refine auditory representation.
Frontoparietal Correlation Dynamics Reveal Interplay between Integration and Segregation during Visual Working Memory
Authors: Dotson Nicholas M. , Salazar Rodrigo F. , Gray Charles M.
Published: October 2014

Working memory requires large-scale cooperation among widespread cortical and subcortical brain regions. Importantly, these processes must achieve an appropriate balance between functional integration and segregation, which are thought to be mediated by task-dependent spatiotemporal patterns of correlated activity. Here, we used cross-correlation analysis to estimate the incidence, magnitude, and relative phase angle of temporally correlated activity from simultaneous local field potential recordings in a network of prefrontal and posterior parietal cortical areas in monkeys performing an oculomotor, delayed match-to-sample task. We found long-range intraparietal and frontoparietal correlations that display a bimodal distribution of relative phase values, centered near 0° and 180°, suggesting a possible basis for functional segregation among distributed networks. Both short- and long-range correlations display striking task-dependent transitions in strength and relative phase, indicating that cognitive events are accompanied by robust changes in the pattern of temporal coordination across the frontoparietal network.
Cortical Activation Associated with Muscle Synergies of the Human Male Pelvic Floor
Authors: Asavasopon Skulpan , Rana Manku , Kirages Daniel J. , Yani Moheb S. , Fisher Beth E. , Hwang Darryl H. , Lohman Everett B. , Berk Lee S. , Kutch Jason J.
Published: October 2014

Human pelvic floor muscles have been shown to operate synergistically with a wide variety of muscles, which has been suggested to be an important contributor to continence and pelvic stability during functional tasks. However, the neural mechanism of pelvic floor muscle synergies remains unknown. Here, we test the hypothesis that activation in motor cortical regions associated with pelvic floor activation are part of the neural substrate for such synergies. We first use electromyographic recordings to extend previous findings and demonstrate that pelvic floor muscles activate synergistically during voluntary activation of gluteal muscles, but not during voluntary activation of finger muscles. We then show, using functional magnetic resonance imaging (fMRI), that a region of the medial wall of the precentral gyrus consistently activates during both voluntary pelvic floor muscle activation and voluntary gluteal activation, but not during voluntary finger activation. We finally confirm, using transcranial magnetic stimulation, that the fMRI-identified medial wall region is likely to generate pelvic floor muscle activation. Thus, muscle synergies of the human male pelvic floor appear to involve activation of motor cortical areas associated with pelvic floor control.
Stress Induces Pain Transition by Potentiation of AMPA Receptor Phosphorylation
Authors: Li Changsheng , Yang Ya , Liu Sufang , Fang Huaqiang , Zhang Yong , Furmanski Orion , Skinner John , Xing Ying , Johns Roger A. , Huganir Richard L. , Tao Feng
Published: October 2014

Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition.
Phasic Activation of Individual Neurons in the Locus Ceruleus/Subceruleus Complex of Monkeys Reflects Rewarded Decisions to Go But Not Stop
Authors: Kalwani Rishi M. , Joshi Siddhartha , Gold Joshua I.
Published: October 2014

Neurons in the brainstem nucleus locus ceruleus (LC) often exhibit phasic activation in the context of simple sensory-motor tasks. The functional role of this activation, which leads to the release of norepinephrine throughout the brain, is not yet understood in part because the conditions under which it occurs remain in question. Early studies focused on the relationship of LC phasic activation to salient sensory events, whereas more recent work has emphasized its timing relative to goal-directed behavioral responses, possibly representing the end of a sensory-motor decision process. To better understand the relationship between LC phasic activation and sensory, motor, and decision processing, we recorded spiking activity of neurons in the LC+ (LC and the adjacent, norepinephrine-containing subceruleus nucleus) of monkeys performing a countermanding task. The task required the monkeys to occasionally withhold planned, saccadic eye movements to a visual target. We found that many well isolated LC+ units responded to both the onset of the visual cue instructing the monkey to initiate the saccade and again after saccade onset, even when it was initiated erroneously in the presence of a stop signal. Many of these neurons did not respond to saccades made outside of the task context. In contrast, neither the appearance of the stop signal nor the successful withholding of the saccade elicited an LC+ response. Therefore, LC+ phasic activation encodes sensory and motor events related to decisions to execute, but not withhold, movements, implying a functional role in goal-directed actions, but not necessarily more covert forms of processing.
El surgimiento de la ganadería en la Ciénega de Chapala (Michoacán, México). El caso de la Hacienda Guaracha (siglos XVI-XIX)
Authors: Dávila Moreno María Elena Nancy
Published: October 2014

En México, durante la Colonia, la ganadería surgió como un instrumento para privatizar las antiguas tierras indígenas y en torno a ésta se fueron generando complejos mecanismos de articulación social, institucionales y de defensa de privilegios de grupos territoriales, lo cual no contempló las devastadoras consecuencias ecológicas que implicaba su desarrollo. El objeto de estudio es la región de la Ciénega de Chapala, Michoacán (México), con el fin de vincular los cambios institucionales con la alteración del espacio físico, así como sus efectos identificando cuáles han sido los eventos a lo largo de la historia que determinaron su actual geografía. La Ciénega de Chapala, ha experimentado un importante grado de alteración en su paisaje, derivado de la apertura a la agricultura y a la ganadería extensiva desde el siglo XVI y, el caso de la Hacienda Guaracha es un ejemplo de cómo ocurrieron estos cambios desde las primeras concentraciones de tierra y agua en el siglo XVI hasta el final del siglo XIX. Palabras clave: ganadería, cambio institucional, estancia ganadera, Ciénega de Chapala, hacienda La Guaracha. The Emergence of Livestock in the Cienega de Chapala (Michoacán, Mexico). The Case of the Hacienda Guaracha (XVI-XIX centuries) AbstractIn Mexico, during the colonial period, livestock emerged as a tool to privatize former Indian lands and around them complex social mechanisms were generated which were institutional articulated to defend the privileges of territorial groups, which did not consider the devastating consequences involving ecological development. The study object is the region of the Cienega de Chapala, Michoacan (México), in order to link institutional changes with the alteration of the physical space as well as their effects by identifying what were the events throughout history that led to its current geography. The Cienega de Chapala has experienced a significant degree of changes in its landscape, derived from the opening to agriculture and extensive livestock since the sixteenth century. The case of Hacienda Guaracha is an example of how these changes occurred from the first land and water concentrations in the sixteenth century to the late nineteenth century.  Key words: livestock, institutional change, cattle ranch, Cienega de Chapala, Hacienda (Ranch) La Guaracha.
A Retrospective 3- to 5-Year Study of the Reconstruction of Oral Function Using Implant-Supported Prostheses in Patients With Hypohidrotic Ectodermal Dysplasia
Authors: Zou Duohong , Wu Yiqun , Wang Xu Dong , Huang Wei , Zhang Zhiyong , Zhang Zhiyuan
Published: October 2014

The aim of this study was to evaluate oral function rehabilitation in patients with hypohidrotic ectodermal dysplasia (HED) using implant-supported prostheses based on bone augmentation. From September 2005 and March 2009, 25 HED patients were chosen for clinical data analysis in this study. The criteria for patient selection included the following: the display of clinical features of HED, the number of congenitally missing teeth (>5), the patient age (>16 years), the patient's willingness, and the patient's tolerance for bone graft surgery and implant placement. Follow-up evaluations were initiated from the time of implant prosthetic placement and scheduled annually for 3–5 years. The effects of oral function reconstruction were assessed based on the cumulative survival and success rates of implants, the health of the peri-implant area, and the degree of patient satisfaction. Twenty-five HED patients received 169 conventional implants and 10 zygomatic implants (179 total implants). During 3–5 years of post-loading evaluations, 5 of the 179 implants failed and 3 implants were removed. The 3-year success and cumulative survival rates were 97.2% and 98.3%, respectively. Furthermore, periodontal probing and radiographic assessments showed that the 3-year incidence of peri-implantitis was 4.5%. Finally, HED patients expressed high degrees of satisfaction with their facial contours, masticatory function, pronunciation ability, and comfort with the implant-supported prostheses. The results of this 3- to 5-year retrospective study indicate that the oral function of HED patients can be effectively reconstructed using bone augmentation and implant-supported prostheses; however, longer term results are warranted in the future.
Soft Tissue Response and Survival of Extraoral Implants: A Long-Term Follow-up
Authors: Balik Ali , Ozdemir-Karatas Meltem , Peker Kadriye , Cifter Ebru Demet , Sancakli Erkan , Gökcen-Röhlig Bilge
Published: October 2014

Maxillofacial defects may be reconstructed by plastic surgery or treated by prosthetic mean rehabilitation. In case of large defects, prosthetic rehabilitation rather than surgical reconstruction is preferred due to the insufficient esthetic results of surgical interventions. However, retention of the craniofacial prosthesis is a great problem despite the satisfactory esthetic results. With the presentation of extraoral implants, the retention of maxillofacial prostheses was improved, and osseointegrated craniofacial implants have become indispensable for retention and stability. However, there are conflicting results regarding the success rates of osseointegrated implants used at the craniofacial region. A total of 24 patients with 64 implants (30 in auricular region of 13 patients, 24 in nasal region of 8 patients, and 10 in orbital region of 3 patients) ranging in age from 16 to 83 years (mean age = 45.45 years) were evaluated. One patient among 13 patients (1/13) has lost his implants in the auricular area, 1 patient among 8 patients (1/8) lost his implants, and 1 patient among 3 patients (1/3) has lost all of her implants. Peri-implant soft tissue response was evaluated for a 60-month period and a total of 654 visits/sites recorded. Grade 0 (no irritation) was present in 72.8% (476/654) of the visits/sites. Grade 1 (slight redness) was observed for 18.8% (123/654). Grade 2 (red and slightly moist tissue) was scored in 6.9% (45/654). Grade 3 (red and slightly moist tissue with granulation) was noted in 1.5% (10/654) and grade 4 (infection) could not be found. Ossseointegrated implants provide reasonable support and show successful results when used with maxillofacial prostheses.