julilili42/papers huggingface dataset:
Malaria Chemoprophylaxis With Atovaquone‐Proguanil: Is a Shorter Regimen Fully Protective?
2014-03-01

As in any other field of medicine, how much evidence do we need in travel medicine before we change daily practice and adapt guidelines and recommendations for prophylaxis or treatment, for example regarding malaria? Leshem and colleagues, rightfully stating that adherence to antimalarial chemoprophylaxis (in this case to atovaquone‐proguanil—AP) may leave room for improvement, and that findings (evidence!) from clinical and pharmacokinetic studies informed such a bold move, put a shortened AP oral chemoprophylactic scheme to the test. Following intake of this regimen—in standard dosage, but only administered from the day before departure up to the day after return—outcomes were surveyed at 6 months post‐travel, resulting in the conclusion that cessation of drug intake straight after return may convey full protection compared to a standard +7 days post‐exposure regimen.1 Correctly taken for the purpose of chemoprophylaxis, suitable antimalarials are considered as being of high efficacy. The problem, however, often is a reduced effectiveness, to which noncompliance (the definition in my view encompassing also not even embarking on a recommended regimen) or nonadherence (not appropriately seeing through the intake of a begun regimen) is a major contributor, as pointed out by Rombo and colleagues in this issue.2 Leshem and colleagues assume a high level of adherence, although their study was not designed to assess it systematically.1 While the authors acknowledge several of the methodological shortcomings (possibly problematic choice of region with limited risk of exposure, insufficient level of evidence that the drugs were taken appropriately, possible recall bias), they suggest that travelers may discontinue AP prophylaxis 1 day after leaving endemic areas, and recommend their approach for further evaluation. In earlier days, what we would now consider as limited evidence may have led to major practice change, as exemplified by the introduction of primaquine for treatment and prophylaxis of vivax ... Corresponding Author: Professor Martin P. Grobusch, MD, PhD, Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22600 1100 DD Amsterdam, The Netherlands. E‐mail: m.p.grobusch{at}amc.uva.nl
Can quantum-chemical NMR chemical shifts be used as criterion for force-field development
2014-03-01

Fragment-based quantum chemical calculations based on our adjustable density matrix assembler (ADMA) are able to calculate NMR chemical shifts even for proteins and protein-protein complexes [1,2]. The agreement between the calculated and experimental chemical shifts in these calculations is, however, highly dependent on including conformational sampling and explicit solvent molecules. On the one hand, ensembles taken from classical MD simulations are suited for 13C and 1H chemical shift calculations if polar protons are neglected [3]. On the other hand, input structures from a Car–Parrinello MD resulted in landmark improvements over calculations based on classical MD especially for amide protons, which are predicted too high-field shifted based on the latter ensembles [4]. The better results are caused by the solute–solvents interactions forming shorter hydrogen bonds as well as by the internal degrees of freedom of the solute. With the obtained accuracy and the possibility of identifying the structural reasons for discrepancies between the experimental and calculated data, NMR chemical-shift calculations are now a perfect tool for e.g. the validation of new, improved force fields.
Thermal vacancies in close-packing solids
2014-03-01

Based on Stillinger's version of cell cluster theory, we derive an expression for the equilibrium concentration of thermal monovacancies in solids which allows for a transparent interpretation of the vacancy volume and the energetic/entropic part in the corresponding Gibbs energy of vacancy formation . For the close--packing crystals of the hard sphere and Lennard--Jones model systems very good agreement with simulation data is found. Application to metals through the embedded--atom method (EAM) reveals a strong sensitivity of the variation of with temperature to details of the EAM potential. Our truncation of the cell cluster series allows for an approximate, but direct measurement of crystal free energies and vacancy concentration in colloidal model systems using laser tweezers.
Rebuilding KEGG Maps: Algorithms and Benefits
2014-03-01

Static drawings of biological pathways are still an important research tool for biologists. Gerhard Michal created his seminal drawings of metabolic networks in the 1960s and thus defined canonical representations of some key pathways. The Kyoto Encyclopedia of Genes and Genomes (KEGG) provides the most popular static drawings of biological networks of different types, used in a huge number of publications. These drawings are so widely known that they are immediately recognizable to most biologists. This enables collaborative work and simplifies the communication of analysis results. Automatic layout of these pathway maps is complicated by the fact that the information available from KEGG does not contain the entire layout information of the reference maps. Here we present a fully automated algorithm for interactive KEGG layout construction. The algorithm conserves the original KEGG layout to the extent possible while improving readability by removing unnecessary elements (in organism-specific maps). Multiple pathway maps can be laid out simultaneously to facilitate the navigation of larger networks. The algorithm supports the hierarchical layout of sub networks and thus supports interactive exploration of large datasets.
What Makes an Oddball Odd? Evidence from a Spatially Predictable Temporal Oddball Paradigm
2014-03-01

The temporal oddball effect (Birngruber, Schröter, and Ulrich, in press; Pariyadath and Eagleman, 2007; Schindel, Rowlands, and Arnold, 2011) describes the finding that rare, deviant stimuli (oddballs) are temporally overestimated as compared to standards of equal physical duration. In a typical oddball paradigm, oddballs are presented at a random position within a stream of repeated standard stimuli. While the standards' duration is constant, oddball duration varies from trial to trial. After each trial, participants are asked to judge whether the oddball was shorter or longer in duration than the standards. In order to explain the oddball effect, it has been assumed that oddballs as compared to standards either attract more attention (Tse, Intriligator, Rivest, & Cavanagh, 2004) or increase the level of arousal (Ulrich, Nitschke, & Rammsayer, 2006). Nevertheless, it is not entirely clear which aspects make an oddball "odd". In the present study, we modified the classical paradigm in order to disentangle different factors that could drive the oddball effect. In each trial, a stream of five stimuli was presented, whereby the first four stimuli were always standards (e.g., blue disks) of a constant standard duration (800 ms) and the last stimulus was a comparison stimulus of varying duration (480-1120 ms; in nine steps). The comparison stimulus could either be another standard (e.g., another blue disk) or an oddball (e.g., a red disk). Participants' task was to judge whether the last stimulus in the stream was shorter or longer than the four preceding stimuli. In order to make counting of the stimuli unnecessary, we presented the stimuli in a spatially predictable format on the screen, that is, on an imagined clock face. Stimuli appeared in clockwise order at the 12, 3, 6, and 9 o'clock positions (standards), and again at the 12 o'clock position (comparison). In half of all trials, a standard stimulus was presented as comparison whereas in the other half of trials an oddball stimulus was presented as comparison. This allowed for a direct comparison of the subjective duration of oddballs and standards. In two separate blocks of trials, we manipulated how many different oddball colors could appear. In one block of trials, only a single oddball color was used (e.g., red) whereas in the other block of trials, four different oddball colors were used (cyan, green, magenta, and yellow) and presented equally often. Points of subjective equality (PSE) were derived from the individual psychometric functions as measures of perceived duration. Preliminary data show that even though all stimuli evoked PSEs smaller than the objective standard duration, no oddball effect was present in either block. Possible explanations for this result pattern will be discussed.
Mechanisms of Multisensory Integration in the Time Domain
2014-03-01

Information from different senses has to be combined in order to form a meaningful and coherent representation of our environment (e.g., Calvert, Spence, & Stein, 2004; Lalanne & Lorenceau, 2004). Because there is no dedicated sense organ for the perception of duration, researchers have been especially interested in understanding which mechanisms govern such a multimodal integration in the domain of time perception (e.g., Chen & Yeh, 2009; Klink, Montijn, & van Wezel, 2011; Romei, De Haas, Mok, & Driver, 2011). In a series of experiments, we investigated to what extent visual and auditory temporal information contribute to a combined temporal percept, and we show that this mutual influence is presumably determined by low-level influences on the perceptual processing stage rather than controlled, decisional processes (Bausenhart, De la Rosa, & Ulrich, in press). Furthermore, we demonstrated that incongruent audiovisual durations seem to be integrated through the occurrence of a temporal ventriloquism effect (De la Rosa & Bausenhart, 2013). In terms of the pacemaker-accumulator model of time perception, this points to an involvement of the switch component rather than to a modulation of the pacemaker rate by incongruent audiovisual information. Moreover, not only temporally incongruent, but also spatially incongruent multimodal information seems to have an influence on perceived duration. Specifically, visuo-spatial information can evoke a Kappa effect (i.e., prolonged perceived duration for intervals defined by spatially separated signals, cf. Cohen, Hansel, & Sylvester, 1953) in the perception of auditory temporal intervals. Taken together, perceived duration is affected by temporal and spatial information from different modalities, which is effectively, flexibly, and rather automatically combined, in order to deliver a coherent and stable perceptual impression.
Natural History and Morphology of the HoverflyPseudomicrodon biluminiferusand Its Parasitic Relationship with Ants Nesting in Bromeliads
2014-03-01

The syrphid subfamily Microdontinae is characterized by myrmecophily of their immature stages, i.e., they develop in ant nests. Data on natural history of microdontines are scarce, especially in the Neotropics. Based on fieldwork in southern Brazil, this study provided new data on development and ecology of the hoverfly Pseudomicrodon biluminiferus (Hull) (Diptera: Syrphidae) as well as the first morphological descriptions of male genitalia, larvae, and pupa. Immature specimens were specifically found in colonies of the ant species Crematogaster limata Smith (Hymenoptera: Formicidae) found in rosettes of the bromeliad species Aechmea lindenii (E. Morren) Baker (Poales: Bromeliaceae) and A. nudicaulis (L.) Grisebach. Third instar larvae were observed preying on ant larvae, revealing the parasitic nature of P. biluminiferus. In this and several other aspects, the natural history of P. biluminiferus is similar to that of Holarctic microdontine species. Exceptions include: (i) indications that adults of P. biluminiferus outlast the winter months (in contrast to 3rd instar larvae in Holarctic species) and (ii) P. biluminiferus' relationship with bromeliads. The importance of bromeliads for this host-parasite system is evaluated in this paper. The single occurrence of another, unidentified microdontine species' pupae in a nest of the ant species Camponotus melanoticus Emery (Hymenoptera: Formicidae) is reported.
Tracheocutaneous fistula closure using a Cartilo-musculo-cutaneous bilobed flap.
2014-03-01

In general, the development of a tracheocutaneous fistula (TCF) after tracheotomy is a seldom but recurrent clinical problem in long-term ventilated patients. In cases of prolonged wound healing with no spontaneous wound closure or insufficient later closure by secondary suture, different surgical procedures have been previously described for the closure of TCFs. Nonetheless, each procedure has its individually associated complications so that definite closure of TCFs still remains a challenge. The purpose of this case report is to present a unique case of a patient with a persistent TCF that was successfully closed using a local cartilo-musculo-cutaneous bilobed flap.
The Cognitive Representation of Time and Duration
2014-03-01

How do people represent the duration of an event in memory and which mechanisms except timing are involved in processing and maintaining temporal information within the cognitive system? The speakers of this symposium will address this and related questions. Anne-Claire Rattat focuses on long-term retention of durations in children and adults. Ruth Ogden discusses executive functions that are involved in timing and time perception. Hedderik van Rijn and Niels Taagten show how general principles of memory and attention can be connected with theories about time perception. Finally, Daniel Bratzke reviews prominent ideas about how temporal information is coded within and across sensory modalities. The titles and abstracts of the four talks are given below.
Symposia
2014-03-01

Increased dietary K + intake has antihypertensive effects, prevents stroke and reduces cardiac hypertrophy.The underlying mechanism for these beneficial effects of a high K + diet are unclear and may include vasodilatation, enhanced urine flow, reduced renin release, and a negative Na + balance in general.The absence of any renal Na + retention and the antihypertensive effect are surprising given the fact that dietary K + loading is known to increase aldosterone secretion and to stimulate sodium absorption in the renal collecting system.The presentation will highlight previous and recent data suggesting that a down-regulation of the thiazide-sensitive NaCl co-transporter in the renal distal convoluted tubule explains a K + -diet-induced natriuresis and likely contributes to the antihypertensive effect of a K +rich diet. S1-03Diverse functions of mineralocorticoids
Temporal Preparation in Choice Reaction Time Tasks: Evidence of Increased Readiness for Task-specific Processing Requirements
2014-03-01

Reaction time usually decreases when an imperative stimulus is preceded by a warning signal, which reduces the temporal uncertainty of the imperative stimulus' onset. This effect has been attributed to temporal preparation and has mainly been investigated by studies manipulating the foreperiod, that is, the interval between the warning signal and the imperative stimulus (Niemi & Näätänen, 1981). The present study investigated to what extent temporal preparation in choice reaction time tasks involves increased readiness for task-specific processing requirements as opposed to increased task-independent readiness. Participants performed a pitch, a letter, or a color discrimination task within a variable foreperiod paradigm. Tasks alternated regularly between auditory and visual discrimination and in separate blocks of trials, the upcoming visual discrimination task was either predictable or unpredictable. We observed the standard variable foreperiod effect for both visual discrimination tasks irrespective of task predictability. Importantly, however, the variable foreperiod effect was larger when the visual discrimination task was predictable than when it was unpredictable. These results suggest that temporal preparation in choice reaction time tasks involves increased readiness for both task-independent and task-specific processing requirements.
S5. Proffered paper: Maintenance therapy of metastatic colorectal carcinoma with the TLR-9 agonist MGN1703: clinical and immunological predictive pretreatment factors of activity in the IMPACT trial
2014-03-01

Meeting abstracts MGN1703 is a synthetic DNA-based immunomodulator acting as TLR-9 agonist which has shown preclinical activity in metastatic colorectal carcinoma (mCRC) as well as a good safety profile in patients with metastatic solid tumours in a Phase 1 trial. The IMPACT trial was conducted to
P69. Targeting naturally presented, leukemia-derived HLA ligands with TCR-transgenic T cells for the treatment of therapy refractory leukemias
2014-03-01

Meeting abstracts T cells have proven to be effective for the treatment of leukaemias in form of donor lymphocyte infusions (DLI). However, those DLI are of unknown specificity and often associated with graft versus host disease. New effector tools in form of T cell receptor (TCR)-transgenic T
Body temperature and heart rate in paediatric SCUBA dives : original research article
2014-03-01

Background : Diving with self-contained underwater breathing apparatus (SCUBA) has become a popular recreational activity in children and adolescents. Compared to adults, children are expected to be at increased risk for hypothermia during SCUBA diving, which may also result in bradycardia. Research question : The objective of this study was to evaluate the occurrence of hypothermia in children during an open-water SCUBA dive and to monitor the heart rate response. Type of study : Single group interventional trial. Methods : Measurements of oral, tympanic and skin temperature at several sites were performed before and after the dive. Heart rate was monitored continuously in 22 children and adolescents aged 10-15 years during a 30 min. dive (mean water temperature 18.7°C). Results : There was a decline in oral (-0.9°C; -2.4%), tympanic (-2.3°C; -6.1%) and chest (-3.7°C; -10.6%), arm (-2.1°C; -6.3%), thigh (-2.1°C; -6.8%), leg (-2.4°C; -7.6%) and forehead (-3.5°C; -9.9%) skin temperature. Mild hypothermia occurred in four subjects. Heart rate declined continuously during the dive and was different 10, 20, 25 and 30 minutes after descent compared to 5 minutes after descent. Bradycardia was related with high mean depth and low water temperature during the dive but not with skin or body temperatures. Conclusions : Significant heat loss and decline in heart rate occur commonly during SCUBA dives in children and adolescents.
Direct Quantification of Cell-Free, Circulating DNA from Unpurified Plasma
2014-03-03

Cell-free DNA (cfDNA) in body tissues or fluids is extensively investigated in clinical medicine and other research fields. In this article we provide a direct quantitative real-time PCR (qPCR) as a sensitive tool for the measurement of cfDNA from plasma without previous DNA extraction, which is known to be accompanied by a reduction of DNA yield. The primer sets were designed to amplify a 90 and 222 bp multi-locus L1PA2 sequence. In the first module, cfDNA concentrations in unpurified plasma were compared to cfDNA concentrations in the eluate and the flow-through of the QIAamp DNA Blood Mini Kit and in the eluate of a phenol-chloroform isoamyl (PCI) based DNA extraction, to elucidate the DNA losses during extraction. The analyses revealed 2.79-fold higher cfDNA concentrations in unpurified plasma compared to the eluate of the QIAamp DNA Blood Mini Kit, while 36.7% of the total cfDNA were found in the flow-through. The PCI procedure only performed well on samples with high cfDNA concentrations, showing 87.4% of the concentrations measured in plasma. The DNA integrity strongly depended on the sample treatment. Further qualitative analyses indicated differing fractions of cfDNA fragment lengths in the eluate of both extraction methods. In the second module, cfDNA concentrations in the plasma of 74 coronary heart disease patients were compared to cfDNA concentrations of 74 healthy controls, using the direct L1PA2 qPCR for cfDNA quantification. The patient collective showed significantly higher cfDNA levels (mean (SD) 20.1 (23.8) ng/ml; range 5.1-183.0 ng/ml) compared to the healthy controls (9.7 (4.2) ng/ml; range 1.6-23.7 ng/ml). With our direct qPCR, we recommend a simple, economic and sensitive procedure for the quantification of cfDNA concentrations from plasma that might find broad applicability, if cfDNA became an established marker in the assessment of pathophysiological conditions.
DEPDC5 mutations in genetic focal epilepsies of childhood
2014-03-03

Recent studies reported DEPDC5 loss‐of‐function mutations in different focal epilepsy syndromes. Here we identified 1 predicted truncation and 2 missense mutations in 3 children with rolandic epilepsy (3 of 207). In addition, we identified 3 families with unclassified focal childhood epilepsies carrying predicted truncating DEPDC5 mutations (3 of 82). The detected variants were all novel, inherited, and present in all tested affected (n = 11) and in 7 unaffected family members, indicating low penetrance. Our findings extend the phenotypic spectrum associated with mutations in DEPDC5 and suggest that rolandic epilepsy, albeit rarely, and other nonlesional childhood epilepsies are among the associated syndromes. Ann Neurol 2014;75:788–792
Clinical Results for use of local anesthesia with epinephrine in penile nerve block
2014-03-03

Summary Background It is widely accepted that local anesthetics with epinephrine should not be used in areas served by terminal vessels. There is no evidence in studies for this in penile surgery, and given the anatomy of the penis, perfusion complications are highly unlikely. The goal of this study was to show that a penile block using a local anesthetic with epinephrine is safe. Patients and Methods In a follow‐up study between 2005 and 2010, we analyzed 95 patients who got a penile ring block with subcutaneous infusion anesthesia (SIA). The SIA solution consisted of ropivacaine and lidocaine (0.11% and 0.21%) plus epinephrine. Results There were no anesthetic complications. Short‐term negative postoperative occurrences (&lt;72 hrs.) were swelling (42%), problems with suture material (22%), pain (19%), hematoma and paresthesia (each 13%), erectile dysfunction (12%), small‐area skin necrosis after wound healing without requiring further surgery (13%), micturition disorders (7%), and wound infection (6%). Two patients on anticoagulation therapy had postoperative bleeding requiring revision surgery. 5% of the patients were given further analgesic sedation. 19% complained about postoperative pain. Persistent complaints (maximum 6 months) were disturbances of skin sensation (7%), swelling (4%), and redness and micturition disorders (3% each). Conclusions Supplementing a local anesthetic with epinephrine in penis operations has many advantages, including high patient satisfaction, relatively painless infiltration, low complication rates, improved view of the operating field, and an extended effect of anesthetics with a prolonged reduction in pain. Because of the anatomy of the organ, there is no risk of necrosis related to using a subcutaneous penile ring block. Thus the view that epinephrine should not be used in penis procedures is obsolete.