Predictability is necessary for closed-loop visual feedback delay adaptation

Rohde M, van Dam L, Ernst MO. Predictability is necessary for closed-loop visual feedback delay adaptation. Journal of Vision. 2014;14(3):4.In case of delayed visual feedback during visuomotor tasks, like in some sluggish computer games, humans can modulate their behavior to compensate for the delay. However, opinions on the nature of this compensation diverge. Some studies suggest that humans adapt to feedback delays with lasting changes in motor behavior (aftereffects) and a recalibration of time perception. Other studies have shown little or no evidence for such semipermanent recalibration in the temporal domain. We hypothesize that predictability of the reference signal (target to be tracked) is necessary for semipermanent delay adaptation. To test this hypothesis, we trained participants with a 200 ms visual feedback delay in a visually guided manual tracking task, varying the predictability of the reference signal between conditions, but keeping reference motion and feedback delay constant. In Experiment 1, we focused on motor behavior. Only training in the predictable condition brings about all of the adaptive changes and aftereffects expected from delay adaptation. In Experiment 2, we used a synchronization task to investigate perceived simultaneity (perceptuomotor learning). Supporting the hypothesis, participants recalibrated subjective visuomotor simultaneity only when trained in the predictable condition. Such a shift in perceived simultaneity was also observed in Experiment 3, using an interval estimation task. These results show that delay adaptation in motor control can modulate the perceived temporal alignment of vision and kinesthetically sensed movement. The coadaptation of motor prediction and target prediction (reference extrapolation) seems necessary for such genuine delay adaptation. This offers an explanation for divergent results in the literature

No need to touch this: Bimanual haptic slant adaptation does not require touch

In our daily life, we often interact with objects using both hands raising the question the question to what extent information between the hands is shared. It has, for instance, been shown that curvature adaptation aftereffects can transfer from the adapted hand to the non-adapted hand. However, this transfer only occurred for dynamic exploration, e.g. by moving a single finger over a surface, but not for static exploration when keeping static contact with the surface and combining the information from different parts of the hand. This raises the question to what extent adaptation to object shape is shared between the hands when both hands are used in static fashion simultaneously and the object shape estimates require information from both hands. Here we addressed this question in three experiments using a slant adaptation paradigm. In Experiment 1 we investigated whether an aftereffect of static bimanual adaptation occurs at all and whether it transfers to conditions in which one hand was moving. In Experiment 2 participants adapted either to a felt slanted surface or simply be holding their hands in mid-air at similar positions, to investigate to what extent the effects of static bimanual adaptation are posture-based rather than object based. Experiment 3 further explored the idea that bimanual adaptation is largely posture based. We found that bimanual adaptation using static touch did lead to aftereffects when using the same static exploration mode for testing. However, the aftereffect did not transfer to any exploration mode that included a dynamic component. Moreover, we found similar aftereffects both with and without a haptic surface. Thus, we conclude that static bimanual adaptation is of proprioceptive nature and does not occur at the level at which the object is represented

Exploration mode affects visuohaptic integration of surface orientation

Plaisier M, van Dam L, Glowania C, Ernst MO. Exploration mode affects visuohaptic integration of surface orientation. Journal of Vision. 2014;14(13):22.We experience the world mostly in a multisensory fashion using a combination of all of our senses. Depending on the modality we can select different exploration strategies for extracting perceptual information. For instance, using touch we can enclose an object in our hand to explore parts of the object in parallel. Alternatively, we can trace the object with a single finger to explore its parts in a serial fashion. In this study we investigated whether the exploration mode (parallel versus serial) affects the way sensory signals are combined. To this end, participants visually and haptically explored surfaces that varied in roll angle and indicated which side of the surface was perceived as higher. In Experiment 1, the exploration mode was the same for both modalities (i.e., both parallel or both serial). In Experiment 2, we introduced a difference in exploration mode between the two modalities (visual exploration was parallel while haptic exploration was serial or vice versa). The results showed that visual and haptic signals were combined in a statistically optimal fashion only when the exploration modes were the same. In case of an asymmetry in the exploration modes across modalities, integration was suboptimal. This indicates that spatial-temporal discrepancies in the acquisition of information in the two senses (i.e., haptic and visual) can lead to the break-down of sensory integration

Effects of Iron and Light Availability on Phytoplankton Photosynthetic Properties in the Ross Sea

Waters of the Southern Ocean are characterized by high macronutrient concentrations but limited availability of trace metals and light, often making it difficult for phytoplankton to achieve maximum growth rates. One strategy employed by Southern Ocean phytoplankton in culture to cope with low light and low dissolved iron (DFe) is to enhance light absorption by increasing their antenna size rather than the number of reaction centers, thereby reducing their Fe demand. Here we provide physiological evidence that natural populations of Southern Ocean phytoplankton employ a similar photoacclimation strategy to cope with low ambient DFe concentrations. During a research cruise to the Ross Sea in 2013-2014, we conducted 4 bioassay experiments in which we manipulated light and DFe concentrations and measured changes in phytoplankton biomass, growth rate, photosynthetic parameters, fluorescence parameters, and pigment composition. Phytoplankton responded strongly to DFe additions, exhibiting significantly higher biomass, growth rates, and photosynthetic competency. At low light, the maximum photosynthetic rate (P*max) was significantly reduced and the photosynthetic efficiency (α*) was unchanged compared to the high light treatment, regardless of phytoplankton species composition or DFe concentration. Our data suggest that Southern Ocean phytoplankton have evolved an Fe-saving strategy whereby they photoacclimate to low light by increasing their photosynthetic unit size, rather than photosynthetic unit number, even when DFe is available. It appears this Fe-saving strategy is characteristic of both Phaeocystis antarctica and diatoms, suggesting that it is a common adaptation among phytoplankton taxa that grow under Fe limitation in the Southern Ocean

Foot and ankle injuries during the Athens 2004 Olympic Games

<p>Abstract</p> <p>Background</p> <p>Major, rare and complex incidents can occur at any mass-gathering sporting event and team medical staff should be appropriately prepared for these. One such event, the Athens Olympic Games in 2004, presented a significant sporting and medical challenge. This study concerns an epidemiological analysis of foot and ankle injuries during the Games.</p> <p>Methods</p> <p>An observational, epidemiological survey was used to analyse injuries in all sport tournaments (men's and women's) over the period of the Games.</p> <p>Results</p> <p>A total of 624 injuries (525 soft tissue injuries and 99 bony injuries) were reported. The most frequent diagnoses were contusions, sprains, fractures, dislocations and lacerations. Significantly more injuries in male (58%) versus female athletes (42%) were recorded. The incidence, diagnosis and cause of injuries differed substantially between the team sports.</p> <p>Conclusion</p> <p>Our experience from the Athens Olympic Games will inform the development of public health surveillance systems for future Olympic Games, as well as other similar mass events.</p

Cigarette Smoke Up-regulates PDE3 and PDE4 to Decrease cAMP in Airway Cells

BACKGROUND AND PURPOSE: 3', 5'-cyclic adenosine monophosphate (cAMP) is a central second messenger that broadly regulates cell function and can underpin pathophysiology. In chronic obstructive pulmonary disease (COPD), a lung disease primarily provoked by cigarette smoke (CS), the induction of cAMP-dependent pathways, via inhibition of hydrolyzing phosphodiesterases (PDEs), is a prime therapeutic strategy. Mechanisms that disrupt cAMP signaling in airway cells, in particular regulation of endogenous PDEs are poorly understood. EXPERIMENTAL APPROACH: We used a novel Förster resonance energy transfer (FRET) based cAMP biosensor in mouse in vivo, ex vivo precision cut lung slices (PCLS), and in human in vitro cell models to track the effects of CS exposure. KEY RESULTS: Under fenoterol stimulated conditions, FRET responses to cilostamide were significantly increased in in vivo, ex vivo PCLS exposed to CS and in human airway smooth muscle cells exposed to CS extract. FRET signals to rolipram were only increased in the in vivo CS model. Under basal conditions, FRET responses to cilostamide and rolipram were significantly increased in in vivo, ex vivo PCLS exposed to CS. Elevated FRET signals to rolipram correlated with a protein upregulation of PDE4 subtypes. In ex vivo PCLS exposed to CS extract, rolipram reversed downregulation of ciliary beating frequency, whereas only cilostamide significantly increased airway relaxation of methacholine pre-contracted airways. CONCLUSION AND IMPLICATIONS: We show that CS upregulates expression and activity of both PDE3 and PDE4, which regulate real-time cAMP dynamics. These mechanisms determine the availability of cAMP and can contribute to CS-induced pulmonary pathophysiology

Granular dot-like staining with MLH1 immunohistochemistry is a clone-dependent artefact

Immunohistochemistry (IHC) for DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6 is used for microsatellite instability (MSI) screening in colorectal carcinoma (CRC) and endometrial carcinoma (EC). Loss of PMS2, with retained MLH1 staining occurs in germline mutations of PMS2 gene, and is an indication for genetic testing. We report a pitfall of immunohistochemical interpretation in an EC, initially regarded as MLH1-positive and PMS2-negative. Review of the MLH1-IHC (M1-clone) revealed a granular, dot-like, nuclear staining. On repeating the MLH1-IHC with a different clone (ES05-clone), complete negativity was noted, and on molecular testing, MLH1 promotor methylation was detected. The dot-like pattern was therefore adjudged a clone-dependent artefact. On reviewing the archived MLH1-IHC slides, we observed the same dot-like pattern in two CRCs; in both cases the M1-clone had been used. Awareness of this artefact may prevent reporting errors, and unnecessary referrals for germline mutation testing

The METEX study: Methotrexate versus expectant management in women with ectopic pregnancy: A randomised controlled trial

Background: Patients with ectopic pregnancy (EP) and low serum hCG concentrations and women with a pregnancy of unknown location (PUL) and plateauing serum hCG levels are commonly treated with systemic methotrexate (MTX). However, there is no evidence that treatment in these particular subgroups of women is necessary as many of these early EPs may resolve spontaneously. The aim of this study is whether expectant management in women with EP or PUL and with low but plateauing serum hCG concentrations is an alternative to MTX treatment in terms of treatment success, future pregnancy, health related quality of life and costs. Methods/Design: A multicentre randomised controlled trial in TheNetherlands. Hemodynamically stable patients with an EP visible on transvaginal ultrasound and a plateauing serum hCG concentration < 1,500 IU/L or with a persisting PUL with plateauing serum hCG concentrations < 2,000 IU/L are eligible for the trial. Patients with a viable EP, signs of tubal rupture/abdominal bleeding, or a contra-indication for MTX will not be included. Expectant management is compared with systemic MTX in a single dose intramuscular regimen (1 mg/ kg) in an outpatient setting. Serum hCG levels are monitored weekly; in case of inadequately declining, systemic MTX is installed or continued. In case of hemodynamic instability and/or signs of tubal rupture, surgery is performed. The primary outcome measure is an uneventful decline of serum hCG to an undetectable level by the initial intervention. Secondary outcomes are (re)interventions (additional systemic MTX injections and/or surgery), treatment complications, health related quality of life, financial costs, and future fertility. Analysis is performed according to the intention to treat principle. Quality of life is assessed by questionnaires before and at three time points after randomisation. Costs are expressed as direct costs with data on costs and used resources in the participating centres. Fertility is assessed by questionnaires after 6, 12, 18 and 24 months. Patients' preferences will be assessed using a discrete choice experiment. Discussion: This trial will provide guidance on the present management dilemmas in women with EPs and PULs with low and plateauing serum hCG concentrations

The Role of Toll-Like Receptor 2 in Inflammation and Fibrosis during Progressive Renal Injury

Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2) is expressed in the kidney and activated by endogenous danger signals. The expression and function of TLR2 during renal fibrosis and chronic inflammation has however not yet been elucidated. Therefore, we studied TLR2 expression in human and murine progressive renal diseases and explored its role by inducing obstructive nephropathy in TLR2−/− or TLR2+/+ mice. We found that TLR2 is markedly upregulated on tubular and tubulointerstitial cells in patients with chronic renal injury. In mice with obstructive nephropathy, renal injury was associated with a marked upregulation and change in distribution of TLR2 and upregulation of murine TLR2 danger ligands Gp96, biglycan, and HMGB1. Notably, TLR2 enhanced inflammation as reflected by a significantly reduced influx of neutrophils and production of chemokines and TGF-β in kidneys of TLR2−/− mice compared with TLR2+/+ animals. Although, the obstructed kidneys of TLR2−/− mice had less interstitial myofibroblasts in the later phase of obstructive nephropathy, tubular injury and renal matrix accumulation was similar in both mouse strains. Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis