Quantifying the turnover of transcriptional subclasses of HIV-1-infected cells

HIV-1-infected cells in peripheral blood can be grouped into different transcriptional subclasses. Quantifying the turnover of these cellular subclasses can provide important insights into the viral life cycle and the generation and maintenance of latently infected cells. We used previously published data from five patients chronically infected with HIV-1 that initiated combination antiretroviral therapy (cART). Patient-matched PCR for unspliced and multiply spliced viral RNAs combined with limiting dilution analysis provided measurements of transcriptional profiles at the single cell level. Furthermore, measurement of intracellular transcripts and extracellular virion-enclosed HIV-1 RNA allowed us to distinguish productive from non-productive cells. We developed a mathematical model describing the dynamics of plasma virus and the transcriptional subclasses of HIV-1-infected cells. Fitting the model to the data allowed us to better understand the phenotype of different transcriptional subclasses and their contribution to the overall turnover of HIV-1 before and during cART. The average number of virus-producing cells in peripheral blood is small during chronic infection. We find that a substantial fraction of cells can become defectively infected. Assuming that the infection is homogenous throughout the body, we estimate an average in vivo viral burst size on the order of 104 virions per cell. Our study provides novel quantitative insights into the turnover and development of different subclasses of HIV-1-infected cells, and indicates that cells containing solely unspliced viral RNA are a good marker for viral latency. The model illustrates how the pool of latently infected cells becomes rapidly established during the first months of acute infection and continues to increase slowly during the first years of chronic infection. Having a detailed understanding of this process will be useful for the evaluation of viral eradication strategies that aim to deplete the latent reservoir of HIV-1.

Sleepiness and performance is disproportionate in patients with non-organic hypersomnia in comparison to patients with narcolepsy and mild to moderate obstructive sleep apnoea.

BACKGROUND/AIMS Clinical differentiation between organic hypersomnia and non-organic hypersomnia (NOH) is challenging. We aimed to determine the diagnostic value of sleepiness and performance tests in patients with excessive daytime sleepiness (EDS) of organic and non-organic origin. METHODS We conducted a retrospective comparison of the multiple sleep latency test (MSLT), pupillography, and the Steer Clear performance test in three patient groups complaining of EDS: 19 patients with NOH, 23 patients with narcolepsy (NAR), and 46 patients with mild to moderate obstructive sleep apnoea syndrome (OSAS). RESULTS As required by the inclusion criteria, all patients had Epworth Sleepiness Scale (ESS) scores >10. The mean sleep latency in the MSLT indicated mild objective sleepiness in NOH (8.1 ± 4.0 min) and OSAS (7.2 ± 4.1 min), but more severe sleepiness in NAR (2.5 ± 2.0 min). The difference between NAR and the other two groups was significant; the difference between NOH and OSAS was not. In the Steer Clear performance test, NOH patients performed worst (error rate = 10.4%) followed by NAR (8.0%) and OSAS patients (5.9%; p = 0.008). The difference between OSAS and the other two groups was significant, but not between NOH and NAR. The pupillary unrest index was found to be highest in NAR (11.5) followed by NOH (9.2) and OSAS (7.4; n.s.). CONCLUSION A high error rate in the Steer Clear performance test along with mild sleepiness in an objective sleepiness test (MSLT) in a patient with subjective sleepiness (ESS) is suggestive of NOH. This disproportionately high error rate in NOH may be caused by factors unrelated to sleep pressure, such as anergia, reduced attention and motivation affecting performance, but not conventional sleepiness measurements.

Increased sleep need and daytime sleepiness 6 months after traumatic brain injury: a prospective controlled clinical trial.

Post-traumatic sleep-wake disturbances are common after acute traumatic brain injury. Increased sleep need per 24 h and excessive daytime sleepiness are among the most prevalent post-traumatic sleep disorders and impair quality of life of trauma patients. Nevertheless, the relation between traumatic brain injury and sleep outcome, but also the link between post-traumatic sleep problems and clinical measures in the acute phase after traumatic brain injury has so far not been addressed in a controlled and prospective approach. We therefore performed a prospective controlled clinical study to examine (i) sleep-wake outcome after traumatic brain injury; and (ii) to screen for clinical and laboratory predictors of poor sleep-wake outcome after acute traumatic brain injury. Forty-two of 60 included patients with first-ever traumatic brain injury were available for follow-up examinations. Six months after trauma, the average sleep need per 24 h as assessed by actigraphy was markedly increased in patients as compared to controls (8.3 ± 1.1 h versus 7.1 ± 0.8 h, P < 0.0001). Objective daytime sleepiness was found in 57% of trauma patients and 19% of healthy subjects, and the average sleep latency in patients was reduced to 8.7 ± 4.6 min (12.1 ± 4.7 min in controls, P = 0.0009). Patients, but not controls, markedly underestimated both excessive sleep need and excessive daytime sleepiness when assessed only by subjective means, emphasizing the unreliability of self-assessment of increased sleep propensity in traumatic brain injury patients. At polysomnography, slow wave sleep after traumatic brain injury was more consolidated. The most important risk factor for developing increased sleep need after traumatic brain injury was the presence of an intracranial haemorrhage. In conclusion, we provide controlled and objective evidence for a direct relation between sleep-wake disturbances and traumatic brain injury, and for clinically significant underestimation of post-traumatic sleep-wake disturbances by trauma patients.

Illegitimate Tasks and Sleep Quality: An Ambulatory Study

The current study investigated the short-term effect of illegitimate tasks on sleep quality, assessed by actigraphy. Seventy-six employees of different service jobs participated in a 2-week data collection. Data were analysed by way of multilevel analyses. As predicted, illegitimate tasks were positively related to sleep fragmentation and sleep-onset latency, but not to sleep efficiency and not to sleep duration. Time pressure, social stressors at work and at home, and the value of the dependent variable from the previous day were controlled. Results confirm the predictive power of illegitimate tasks for a variable that can be considered crucial in the development of long-term outcomes of daily experiences.

A Vertical Asymmetry in Saccades

Visual exploration of natural scenes imposes demands that differ between the upper and the lower visual hemifield. Yet little is known about how ocular motor performance is affected by the location of visual stimuli or the direction of a behavioural response. We compared saccadic latencies between upper and lower hemifield in a variety of conditions, including short-latency prosaccades, long-latency prosaccades, antisaccades, memory-guided sac- cades and saccades with increased attentional and selection demand. All saccade types, except memory guided saccades, had shorter latencies when saccades were directed to- wards the upper field as compared to downward saccades (p<0.05). This upper field reaction time advantage probably arises in ocular motor rather than visual processing. It may originate in structures involved in motor preparation rather than execution.

Reduction of cement leakage by sequential PMMA application in a vertebroplasty model

PURPOSE Leakage is the most common complication of percutaneous cement augmentation of the spine. The viscosity of the polymethylmethacrylate (PMMA) cement is strongly correlated with the likelihood of cement leakage. We hypothesized that cement leakage can be reduced by sequential cement injection in a vertebroplasty model. METHODS A standardized vertebral body substitute model, consisting of aluminum oxide foams coated by acrylic cement with a preformed leakage path, simulating a ventral vein, was developed. Three injection techniques of 6 ml PMMA were assessed: injection in one single step (all-in-one), injection of 1 ml at the first and 5 ml at the second step with 1 min latency in-between (two-step), and sequential injection of 0.5 ml with 1-min latency between the sequences (sequential). Standard PMMA vertebroplasty cement was used; each injection type was tested on ten vertebral body substitute models with two possible leakage paths per model. Leakage was assessed by radiographs using a zonal graduation: intraspongious = no leakage and extracortical = leakage. RESULTS The leakage rate was significantly lower in the "sequential" technique (2/20 leakages) followed by "two-step" (15/20) and "all-in-one" (20/20) techniques (p < 0.001). The RR for a cement leakage was 10.0 times higher in the "all-in-one" compared to the "sequential" group (95 % confidence intervals 2.7-37.2; p < 0.001). CONCLUSIONS The sequential cement injection is a simple approach to minimize the risk for leakage. Taking advantage of the temperature gradient between body and room temperature, it is possible to increase the cement viscosity inside the vertebra while keeping it low in the syringe. Using sequential injection of small cement volumes, further leakage paths are blocked before further injection of the low-viscosity cement.

The modulation of reading strategies by language opacity in early bilinguals: an eye movement study

Converging evidences from eye movement experiments indicate that linguistic contexts influence reading strategies. However, the question of whether different linguistic contexts modulate eye movements during reading in the same bilingual individuals remains unresolved. We examined reading strategies in a transparent (German) and an opaque (French) language of early, highly proficient French–German bilinguals: participants read aloud isolated French and German words and pseudo-words while the First Fixation Location (FFL), its duration and latency were measured. Since transparent linguistic contexts and pseudo-words would favour a direct grapheme/phoneme conversion, the reading strategy should be more local for German than for French words (FFL closer to the beginning) and no difference is expected in pseudo-words’ FFL between contexts. Our results confirm these hypotheses, providing the first evidence that the same individuals engage different reading strategy depending on language opacity, suggesting that a given brain process can be modulated by a given context.

Differential effect of elevated intralabyrinthine pressure on ocular vestibular evoked myogenic potentials elicited by air conducted sound and bone conducted vibration

Recently, ocular vestibular evoked myogenic potentials (oVEMP) have emerged as a tool for assessment of utricular function. They are short-latency myogenic potentials which can be elicited in response to vestibular stimulation, e.g. by air-conducted sound (ACS) or bone-conducted vibration (BCV) (reviewed in (Kantner and Gurkov, 2012)). Otolithic afferent neurons trigger reflexive electromyographic activity of the extraocular muscles which can be recorded beneath the eye contralateral to the stimulated ear by use of surface electrodes.

Perseveration in a guessing task by laying hens selected for high or low levels of feather pecking does not support classification of feather pecking as a stereotypy.

Feather pecking is a behaviour by which birds damage or destroy the feathers of themselves (self-pecking) or other birds (allo feather pecking), in some cases even plucking out feathers and eating these. The self-pecking is rarely seen in domestic laying hens but is not uncommon in parrots. Feather pecking in laying hens has been described as being stereotypic, i.e. a repetitive invariant motor pattern without an obvious function, and indeed the amount of self-pecking in parrots was found to correlate positively with the amount of recurrent perseveration (RP), the tendency to repeat responses inappropriately, which in humans and other animals was found to correlate with stereotypic behaviour. In the present experiment we set out to investigate the correlation between allo feather pecking and RP in laying hens. We used birds (N = 92) from the 10th and 11th generation (G10 and G11) of lines selectively bred for high feather pecking (HFP) and low feather pecking (LFP), and from an unselected control line (CON) with intermediate levels of feather pecking. We hypothesised that levels of RP would be higher, and the time taken (standardised latency) to repeat a response lower, in HFP compared to LFP hens, with CON hens in between. Using a two-choice guessing task, we found that lines differed significantly in their levels of RP, with HFP unexpectedly showing lower levels of RP than CON and LFP. Latency to make a repeat did not differ between lines. Latency to make a switch differed between lines with a shorter latency in HFP compared to LFP (in G10), or CON (in G11). Latency to peck for repeats vs. latency to peck for switches did not differ between lines. Total time to complete the test was significantly shorter in HFP compared to CON and LFP. Thus, our hypotheses were not supported by the data. In contrast, selection for feather pecking seems to induce the opposite effects than would be expected from stereotyping animals: pecking was less sequenced and reaction to make a switch and to complete the test was lower in HFP. This supports the hyperactivity-model of feather pecking, suggesting that feather pecking is related to a higher general activity, possibly due to changes in the dopaminergic system.

Wirkungen monetärer Anreize auf Antworten zur eigenen Delinquenz bei postalischer Befragung

Im vorliegenden Beitrag werden die Ergebnisse einer in dieser Zeitschrift erschienen Studie von Skarbek-Kozietulska, Preisendörfer & Wolter (2012) über die Validität der Antworten straffällig gewordener Befragter aufgegriffen. Die Autoren stellten einen negativen Effekt der Antwortlatenz fest, demzufolge spät Antwortende eher dazu neigen, ihre Straftaten zu leugnen. Die Gründe hierfür vermuten die Autoren in den Eigenheiten der TDM (tailored design method), speziell in wiederholten Nachfassaktionen. Wir untersuchen im Rahmen eines Methodenexperimentes, ob ebenfalls monetäre Anreize als weiterer zentraler Bestandteil der TDM diesen negativen Latenzeffekt für die Antwortbereitschaft verursachen können. Die These, dass der Zusammenhang von Latenz und Validität selbstberichteter Delinquenz über monetäre Anreize moderiert wird, wird dabei empirisch widerlegt.

Edge caching with mobility prediction in virtualized LTE mobile networks

Abstract Mobile Edge Computing enables the deployment of services, applications, content storage and processing in close proximity to mobile end users. This highly distributed computing environment can be used to provide ultra-low latency, precise positional awareness and agile applications, which could significantly improve user experience. In order to achieve this, it is necessary to consider next-generation paradigms such as Information-Centric Networking and Cloud Computing, integrated with the upcoming 5th Generation networking access. A cohesive end-to-end architecture is proposed, fully exploiting Information-Centric Networking together with the Mobile Follow-Me Cloud approach, for enhancing the migration of content-caches located at the edge of cloudified mobile networks. The chosen content-relocation algorithm attains content-availability improvements of up to 500 when a mobile user performs a request and compared against other existing solutions. The performed evaluation considers a realistic core-network, with functional and non-functional measurements, including the deployment of the entire system, computation and allocation/migration of resources. The achieved results reveal that the proposed architecture is beneficial not only from the users’ perspective but also from the providers point-of-view, which may be able to optimize their resources and reach significant bandwidth savings.

Eye Gaze Behavior at Turn Transition: How Aphasic Patients Process Speakers' Turns during Video Observation

The human turn-taking system regulates the smooth and precise exchange of speaking turns during face-to-face interaction. Recent studies investigated the processing of ongoing turns during conversation by measuring the eye movements of noninvolved observers. The findings suggest that humans shift their gaze in anticipation to the next speaker before the start of the next turn. Moreover, there is evidence that the ability to timely detect turn transitions mainly relies on the lexico-syntactic content provided by the conversation. Consequently, patients with aphasia, who often experience deficits in both semantic and syntactic processing, might encounter difficulties to detect and timely shift their gaze at turn transitions. To test this assumption, we presented video vignettes of natural conversations to aphasic patients and healthy controls, while their eye movements were measured. The frequency and latency of event-related gaze shifts, with respect to the end of the current turn in the videos, were compared between the two groups. Our results suggest that, compared with healthy controls, aphasic patients have a reduced probability to shift their gaze at turn transitions but do not show significantly increased gaze shift latencies. In healthy controls, but not in aphasic patients, the probability to shift the gaze at turn transition was increased when the video content of the current turn had a higher lexico-syntactic complexity. Furthermore, the results from voxel-based lesion symptom mapping indicate that the association between lexico-syntactic complexity and gaze shift latency in aphasic patients is predicted by brain lesions located in the posterior branch of the left arcuate fasciculus. Higher lexico-syntactic processing demands seem to lead to a reduced gaze shift probability in aphasic patients. This finding may represent missed opportunities for patients to place their contributions during everyday conversation.