Does value-based prioritization at working memory enhance long-term memory?

Research has demonstrated that individuals can direct their attention to valuable information in both working memory and long-term memory tasks with observable effects on performance. However, it is currently unclear whether prioritising an item for a working memory task automatically translates into a boost at long-term memory. This was examined in two experiments using relatively short (250 ms per item; Experiment 1) and longer (500 ms per item; Experiment 2) encoding times. Participants first completed a visual working memory task, in which they were presented with series of photographs of everyday objects. Following a brief delay (1,000 ms), they completed a four-alternative forced-choice test. Prior to encoding, participants were informed of the point values associated with each item. In some trials, the first item in the sequence was worth more points than the rest. In other trials, all items were equally valuable. After a filled delay, participants completed a surprise long-term memory task. At working memory, a value effect was reliably observed on recognition accuracy, along with some evidence of faster response times for high-value items. However, there was little consistent evidence of this effect automatically persisting into long-term memory. Thus, the benefits of attentional prioritization in working memory do not always translate into longer-term performance. More broadly, this provides further evidence that manipulations that enhance working memory performance do not necessarily enhance long-term memory.

Classifying the unclassifiable-a Delphi study to reach consensus on the fibrotic nature of diseases.

BACKGROUND: Traditionally, clinical research has focused on individual fibrotic diseases or fibrosis in a particular organ. However, it is possible for people to have multiple fibrotic diseases. While multi-organ fibrosis may suggest shared pathogenic mechanisms, yet there is no consensus on what constitutes a fibrotic disease and therefore fibrotic multimorbidity. AIM: A Delphi study was performed to reach consensus on which diseases may be described as fibrotic. METHODS: Participants were asked to rate a list of diseases, sub-grouped according to eight body regions, as 'fibrotic manifestation always present', 'can develop fibrotic manifestations', 'associated with fibrotic manifestations' or 'not fibrotic nor associated'. Classifications of 'fibrotic manifestation always present' and 'can develop fibrotic manifestations' were merged and termed 'fibrotic'. Clinical consensus was defined according to the interquartile range, having met a minimum number of responses. Clinical agreement was used for classification where diseases did not meet the minimum number of responses (required for consensus measure), were only classified if there was 100% consensus on disease classification. RESULTS: After consulting experts, searching the literature and coding dictionaries, a total of 323 non-overlapping diseases which might be considered fibrotic were identified; 92 clinical specialists responded to the first round of the survey. Over three survey rounds, 240 diseases were categorized as fibrotic via clinical consensus and 25 additional diseases through clinical agreement. CONCLUSION: Using a robust methodology, an extensive list of diseases was classified. The findings lay the foundations for studies estimating the burden of fibrotic multimorbidity, as well as investigating shared mechanisms and therapies.

Stochastic Methods for Inferring States of Cell Migration.

Cell migration refers to the ability of cells to translocate across a substrate or through a matrix. To achieve net movement requires spatiotemporal regulation of the actin cytoskeleton. Computational approaches are necessary to identify and quantify the regulatory mechanisms that generate directed cell movement. To address this need, we developed computational tools, based on stochastic modeling, to analyze time series data for the position of randomly migrating cells. Our approach allows parameters that characterize cell movement to be efficiently estimated from cell track data. We applied our methods to analyze the random migration of Mouse Embryonic Fibroblasts (MEFS) and HeLa cells. Our analysis revealed that MEFs exist in two distinct states of migration characterized by differences in cell speed and persistence, whereas HeLa cells only exhibit a single state. Further analysis revealed that the Rho-family GTPase RhoG plays a role in determining the properties of the two migratory states of MEFs. An important feature of our computational approach is that it provides a method for predicting the current migration state of an individual cell from time series data. Finally, we applied our computational methods to HeLa cells expressing a Rac1 biosensor. The Rac1 biosensor is known to perturb movement when expressed at overly high concentrations; at these expression levels the HeLa cells showed two migratory states, which correlated with differences in the spatial distribution of active Rac1.

Calcium Sensitive Fluorescent Dyes Fluo-4 and Fura Red under Pressure: Behaviour of Fluorescence and Buffer Properties under Hydrostatic Pressures up to 200 MPa.

The fluorescent Ca2+ sensitive dyes Fura Red (ratiometric) and Fluo-4 (non-ratiometric) are widely utilized for the optical assessment of Ca2+ fluctuations in vitro as well as in situ. The fluorescent behavior of these dyes is strongly depends on temperature, pH, ionic strength and pressure. It is crucial to understand the response of these dyes to pressure when applying calcium imaging technologies in the field of high pressure bioscience. Therefore, we use an optically accessible pressure vessel to pressurize physiological Ca2+-buffered solutions at different fixed concentrations of free Ca2+ (1 nM to 25.6 µM) and a specified dye concentration (12 µM) to pressures of 200 MPa, and record dye fluorescence intensity. Our results show that Fluo-4 fluorescence intensity is reduced by 31% per 100 MPa, the intensity of Fura Red is reduced by 10% per 100 MPa. The mean reaction volume for the dissociation of calcium from the dye molecules [Formula: see text] is determined to -17.8 ml mol-1 for Fluo-4 and -21.3 ml mol-1 for Fura Red. Additionally, a model is presented that is used to correct for pressure-dependent changes in pH and binding affinity of Ca2+ to EGTA, as well as to determine the influence of these changes on dye fluorescence.

Efficient Generation and Selection of Virtual Populations in Quantitative Systems Pharmacology Models.

Quantitative systems pharmacology models mechanistically describe a biological system and the effect of drug treatment on system behavior. Because these models rarely are identifiable from the available data, the uncertainty in physiological parameters may be sampled to create alternative parameterizations of the model, sometimes termed "virtual patients." In order to reproduce the statistics of a clinical population, virtual patients are often weighted to form a virtual population that reflects the baseline characteristics of the clinical cohort. Here we introduce a novel technique to efficiently generate virtual patients and, from this ensemble, demonstrate how to select a virtual population that matches the observed data without the need for weighting. This approach improves confidence in model predictions by mitigating the risk that spurious virtual patients become overrepresented in virtual populations.

Automated line scan analysis to quantify biosensor activity at the cell edge.

Biosensors are valuable tools used to image the subcellular localization and kinetics of protein activity in living cells. Signaling at the edge of motile cells that regulates cell protrusion and retraction is important in many aspects of cell physiology, and frequently studied using biosensors. However, quantitation and interpretation is limited by the heterogeneity of this signaling behavior; automated analytical approaches are required to systematically extract large data sets from biosensor studies for statistical analysis. Here we describe an automated analysis to relate the velocity at specific points along the cell edge with biosensor activity in adjoining regions. Time series of biosensor images are processed to interpolate a smooth edge of the cell at each time point. Profiles of biosensor activity ('line scans') are then calculated along lines perpendicular to the cell edge. An energy minimization method is used to calculate a velocity associated with each line scan. Sorting line scans by the proximal velocity has generated novel biological insights, as exemplified by analysis of the Src merobody biosensor. With the large data sets that can be generated automatically by this program, conclusions can be drawn that are not apparent from qualitative or 'manual' quantitative techniques. Our 'LineScan' software includes a graphical user interface (GUI) to facilitate application in other studies. It is available at hahnlab.com and is exemplified here in a study using the RhoC FLARE biosensor.

Memory for actions in autism spectrum disorder.

This study explored how memory for actions in children with autism spectrum disorder (ASD) and typically developing children might benefit from self-performance and experimenter demonstration, and whether these groups possess metamemory knowledge of their performance levels in this task. Children with autism were less accurate on the action memory task when they carried out each action themselves during encoding, or when no actions were implemented during this phase, but this difference was abolished when the experimenter demonstrated each action during encoding. Despite clear difficulties in the self-performed condition relative to typical children, the group with ASD also showed a beneficial effect of performing the actions themselves during instruction. Finally, children with autism were as accurate as typical children in judging the accuracy of their own memory performance, indicating an absence of metamemory difficulties for this task.

A model of localised Rac1 activation in endothelial cells due to fluid flow.

Endothelial cells respond to fluid flow by elongating in the direction of flow. Cytoskeletal changes and activation of signalling molecules have been extensively studied in this response, including: activation of receptors by mechano-transduction, actin filament alignment in the direction of flow, changes to cell-substratum adhesions, actin-driven lamellipodium extension, and localised activation of Rho GTPases. To study this process we model the force over a single cell and couple this to a model of the Rho GTPases, Rac and Rho, via a Kelvin-body model of mechano-transduction. It is demonstrated that a mechano-transducer can respond to the normal component of the force is likely to be a necessary component of the signalling network in order to establish polarity. Furthermore, the rate-limiting step of Rac1 activation is predicted to be conversion of Rac-GDP to Rac-GTP, rather than activation of upstream components. Modelling illustrates that the aligned endothelial cell morphology could attenuate the signalling network.

Non-equilibrium dynamics of an active colloidal "chucker".

We report Monte Carlo simulations of the dynamics of a "chucker," a colloidal particle that emits smaller solute particles from its surface, isotropically and at a constant rate k(c). We find that the diffusion constant of the chucker increases for small k(c), as recently predicted theoretically. At large k(c), the chucker diffuses more slowly due to crowding effects. We compare our simulation results to those of a "point particle" Langevin dynamics scheme in which the solute concentration field is calculated analytically, and in which hydrodynamic effects arising from colloid-solvent surface interactions can be accounted for in a coarse-grained way. By simulating the dragging of a chucker, we obtain an estimate of its apparent mobility coefficient which violates the fluctuation-dissipation theorem. We also characterize the probability density profile for a chucker which sediments onto a surface which either repels or absorbs the solute particles, and find that the steady state distributions are very different in the two cases. Our simulations are inspired by the biological example of exopolysaccharide-producing bacteria, as well as by recent experimental, simulation and theoretical work on phoretic colloidal "swimmers."

Safety and immunogenicity of AS03B adjuvanted split virion versus non-adjuvanted whole virion H1N1 influenza vaccine in UK children aged 6 months-12 years: open label, randomised, parallel group, multicentre study.

OBJECTIVES: To compare the safety, reactogenicity, and immunogenicity of an adjuvanted split virion H1N1 vaccine and a non-adjuvanted whole virion vaccine used in the pandemic immunisation programme in the United Kingdom. DESIGN: Open label, randomised, parallel group, phase II study. SETTING: Five UK centres (Oxford, Southampton, Bristol, Exeter, and London). PARTICIPANTS: Children aged 6 months to less than 13 years for whom a parent or guardian had provided written informed consent and who were able to comply with study procedures were eligible. Those with laboratory confirmed pandemic H1N1 influenza or clinically diagnosed disease meriting antiviral treatment, allergy to egg or any other vaccine components, or coagulation defects, or who were severely immunocompromised or had recently received blood products were excluded. Children were grouped by age: 6 months-<3 years (younger group) and 3-<13 years (older group). Recruitment was by media advertising and direct mailing. Recruitment visits were attended by 949 participants, of whom 943 were enrolled and 937 included in the per protocol analysis. INTERVENTIONS: Participants were randomised 1:1 to receive AS03(B) (tocopherol based oil in water emulsion) adjuvanted split virion vaccine derived from egg culture or non-adjuvanted whole virion vaccine derived from cell culture. Both were given as two doses 21 days apart. Reactogenicity data were collected for one week after immunisation by diary card. Serum samples were collected at baseline and after the second dose. MAIN OUTCOME MEASURES: Primary reactogenicity end points were frequency and severity of fever, tenderness, swelling, and erythema after vaccination. Immunogenicity was measured by microneutralisation and haemagglutination inhibition assays. The primary immunogenicity objective was a comparison between vaccines of the percentage of participants showing seroconversion by the microneutralisation assay (fourfold rise to a titre of >or=1:40 from before vaccination to three weeks after the second dose). RESULTS: Seroconversion rates were higher after the adjuvanted split virion vaccine than after the whole virion vaccine, most notably in the youngest children (163 of 166 participants with paired serum samples (98.2%, 95% confidence interval 94.8% to 99.6%) v 157 of 196 (80.1%, 73.8% to 85.5%), P<0.001) in children under 3 years and 226 of 228 (99.1%, 96.9% to 99.9%) v 95.9%, 92.4% to 98.1%, P=0.03) in those over 3 years). The adjuvanted split virion vaccine was more reactogenic than the whole virion vaccine, with more frequent systemic reactions and severe local reactions in children aged over 5 years after dose one (13 (7.2%, 3.9% to 12%) v 2 (1.1%, 0.1% to 3.9%), P<0.001) and dose two (15 (8.5%, 4.8% to 13.7%) v 2 (1.1%, 0.1% to 4.1%), P<0.002) and after dose two in those under 5 years (15 (5.9%, 3.3% to 9.6%) v 0 (0.0%, 0% to 1.4%), P<0.001). Dose two of the adjuvanted split virion vaccine was more reactogenic than dose one, especially for fever >or=38 masculineC in those aged under 5 (24 (8.9%, 5.8% to 12.9%) v 57 (22.4%, 17.5% to 28.1%), P<0.001). CONCLUSIONS: In this first direct comparison of an AS03(B) adjuvanted split virion versus whole virion non-adjuvanted H1N1 vaccine, the adjuvanted vaccine, while more reactogenic, was more immunogenic and, importantly, achieved high seroconversion rates in children aged less than 3 years. This indicates the potential for improved immunogenicity of influenza vaccines in this age group. TRIAL REGISTRATION: Clinical trials.gov NCT00980850; ISRCTN89141709.

Long-term visual outcome after extraction of unilateral congenital cataracts.

BACKGROUND: Congenital cataract significantly impairs visual development. Although treatable, a good visual outcome is difficult to achieve, requiring prompt lensectomy and prolonged visual rehabilitation. PURPOSE: The aim of this study was to investigate whether useable visual acuity (VA) is a realistic goal in these patients. METHODS: A retrospective case review from a tertiary referral centre was performed. This study included children with unilateral congenital cataract who underwent cataract surgery with posterior capsulectomy and anterior vitrectomy. RESULTS: A total of 62 patients were identified. Of them, 32% of aphakic eyes had a final VA of 0.6 LogMAR or better (average 0.34+/-0.17). The average age at the time of surgery was 5.0+/-4.1 weeks. The remaining 68% had vision that was less than 0.6, with 27% having vision of <1.00. The group with vision less than 0.6 (68%) had an average age of 9.7+/-6.5 weeks at the time of surgery. One case (1.6%) achieved a VA of 0.0 and also had demonstrable stereoacuity (110 arc s). Manifest strabismus was present in 85% of cases. Glaucoma developed in 19% of patients and 31% discontinued the occlusion regime before the age of 4 years. In most of these cases, occlusion was ceased by the age of 2 years when testing revealed dense amblyopia in the aphakic eye even if good compliance had previously been achieved. In many cases, this coincided with the child becoming noncompliant with occlusion. CONCLUSIONS: More than two-thirds of children in our cohort did not develop acuity better than 0.6 LogMAR in their aphakic eye.

Time-resolved voltage measurements of Z-pinch radiation sources with a vacuum voltmeter.

A vacuum-voltmeter (VVM) was fielded on the Saturn pulsed power generator during a series of argon gas-puff Z-pinch shots. Time-resolved voltage and separately measured load current are used to determine several dynamic properties as the load implodes, namely, the inductance, L(t), net energy coupled to the load, E(coupled)(t), and the load radius, r(t). The VVM is a two-stage voltage divider, designed to operate at voltages up to 2 MV. The VVM is presently being modified to operate at voltages up to 6 MV for eventual use on the Z generator.

Applanation tonometry in silicone hydrogel contact lens wearers.

INTRODUCTION: Previous studies have investigated intraocular pressure (IOP) measurements through conventional soft (hydrogel) therapeutic contact lenses, and have found that an accurate IOP can be recorded in normal eyes, and in eyes with abnormal anterior segments. The IOP measurement through soft contact lenses may be affected by the water content and centre thickness of the lens. Silicone hydrogel contact lenses are now being used as therapeutic contact lenses due to their high oxygen permeability. The purpose of this study is to investigate if IOP can be accurately measured in a subject wearing a silicone hydrogel contact lens. METHODS: In a cohort study, the IOP was measured with a Goldmann applanation tonometer without a contact lens and then repeated with a hydrogel contact lens in situ. RESULTS: The IOP of 20 eyes of 10 volunteers with no ocular pathology was measured. The mean difference (+/-S.D.) found between IOP measurement with (mean 15.55+/-1.70 mmHg) and without (mean 16.05+/-1.90 mmHg) contact lens was found to be -0.5+/-0.89 mmHg. Statistical analysis was performed which revealed a correlation coefficient of 0.89. No significant statistical difference was found between the two groups with paired t-test (p=0.19). CONCLUSION: Accurate measurement of IOP by applanation tonometry can be achieved through a silicone hydrogel contact lens.

Colgajos de perforantes de arteria glútea superior y arteria glútea inferior / Gluteal artery perforator flaps: S-GAP and I-GAP

En la actualidad la transferencia de tejido ha evolucionado hasta el nivel de los colgajos de perforantes, los cuales aportan tejido formado por piel y grasa, con la mínima morbilidad a nivel de la zona donante. Los colgajos de perforantes de la región glútea, de arteria glutea superior (S-GAP) y de arteria glútea inferior (I-GAP), han ganado popularidad debido a su fiabilidad, preservación del músculo, versatilidad en el diseño sin comprometer otras alternativas reconstructivas y por su baja morbilidad. Se analizarán en este artículo de forma detallada la anatomía, técnica quirúrgica e indicaciones específicas de estos colgajos de perforantes de la región glútea (AU)

The evolution of free tissue transfer has progressed to the level of the perforator flaps. They allow the transfer of the patient´s own skin and fat in a reliable way with minimal donor-site morbidity. Nowadays the gluteal artery perforator flaps, superior (S-GAP) and inferior (I-GAP), have gained popularity due to reliability, preservation of the muscle, versatility in flap design without restricting other flap options, and lower donor-site morbidity. Anatomy of the gluteal region, flap raising technique and specific indications will be well-described (AU)

Electric field-controlled water permeation coupled to ion transport through a nanopore.

We report molecular dynamics simulations of a generic hydrophobic nanopore connecting two reservoirs which are initially at different Na(+) concentrations, as in a biological cell. The nanopore is impermeable to water under equilibrium conditions, but the strong electric field caused by the ionic concentration gradient drives water molecules in. The density and structure of water in the pore are highly field dependent. In a typical simulation run, we observe a succession of cation passages through the pore, characterized by approximately bulk mobility. These ion passages reduce the electric field, until the pore empties of water and closes to further ion transport, thus providing a possible mechanism for biological ion channel gating.

Perforator flaps--the history of evolution.

This article reviews the recent evolution of perforator flaps. The tie between perforator flaps and skin flaps as well as perforator flaps and musculocutaneous flaps is explained. The paraumbilical perforator flap, the deep inferior epigastric artery flap (DIEP flap), the gluteal artery perforator flap (GAP flap) and various perforator flaps and perforator-based flaps are described in combination with the review of the relevant literature. As a prospect into the future, the technique of "supra-microsurgery" is presented.

Reconstruction of a parotidectomy defect using a paraumbilical perforator flap without deep inferior epigastric vessels.

A 37-year-old woman who underwent a parotidectomy for acinic cell carcinoma was referred for correction of the resulting defect. As an assistant principal, the patient was often in public and, because she was somewhat self-conscious about her facial deformity, she sought reconstruction. Physical examination revealed a pre-auricular soft-tissue defect that measured approximately 5 x 5 cm. After consultation with the patient, microsurgical transfer of fat from the lower abdomen based on branches of the deep inferior epigastric vessels, rather than the deep inferior epigastric artery and vein itself, was planned. A vertical skin ellipse measuring 6 x 5 cm was raised from the right lower abdomen with a pedicle consisting of only a branch of the deep inferior epigastric artery and vein. The donor vessels were then microsurgically anastomosed to the superficial temporal artery and vein on the left side of the face. Two weeks postoperatively the flap was defatted, with removal of the skin-monitoring island. The patient continues to do well with a normal contour of the face and decreased anxiety secondary to correction of her facial deformity.

Cost-based comparison between perforator flaps and TRAM flaps for breast reconstruction.

More women than ever before are undergoing mastectomies secondary to increased awareness and screening. This increase has also caused a corresponding increase in the number of breast reconstructions requested each year. The increased demand for reconstruction has fueled recent advances in new techniques. Aside from foreign-body reconstruction such as implants, the methods now being used are related to autogenous donations and reconstruction. Transverse rectus abdominis myocutaneous (TRAM) flaps and perforator flaps are currently being used for autogenous breast reconstruction. This study will compare these two techniques on the basis of cost and length of stay. A retrospective study of 49 patients undergoing a total of 64 perforator flap breast reconstructions at Memorial Medical Center in New Orleans, Louisiana, during the 1997 calendar year was used. There were 59 deep inferior epigastric perforator and five gluteal artery perforator breast reconstructions. All patients underwent some form of breast reconstruction and differed only in respect to whether a mastectomy was performed and whether the reconstruction was unilateral or bilateral. Those patients who underwent a mastectomy with immediate perforator flap reconstruction (n = 26) were then compared with patients undergoing mastectomy with immediate TRAM flap reconstruction (n = 154) at the University of Texas M. D. Anderson Cancer Center. The data from the Anderson Study were obtained from material published in Plastic and Reconstructive Surgery in 1996. Comparison of patients was limited to those who underwent mastectomy with immediate breast reconstruction because this was the design of the M. D. Anderson study. This approach allowed a cost and length of stay comparison while keeping other variables relatively similar. Patients in the perforator flap series enjoyed a marginally shorter operating time and a much shorter length of stay. On average, the operative time for all perforator flap reconstructions was approximately 2 hours shorter than for all TRAM flaps. As for length of stay, perforator flap patients were discharged, on average, 3 days after the initial reconstruction. In contrast, TRAM flap patients remained in the hospital for an average of approximately 7 days after the initial reconstruction. The overall total, average cost for the perforator flap reconstruction in this study is $9625, whereas the average cost of all TRAM flaps performed in the Anderson study is $18,070.

Clinician judgement as a tool for targeting HIV counseling and testing in North Carolina state mental hospitals, 1994.

HIV infection increasingly affects populations that may not appear at high risk based on the use of some traditional targeting strategies. To shed some light on how to more sensitively/effectively identify people who need routine HIV testing and counseling, the objective of this study is to determine the prevalence of HIV infection in North Carolina state mental hospitals and to evaluate clinician judgment as a tool for targeting HIV counseling and testing. The design used is a blinded seroprevalence study. The study population includes all patients admitted to North Carolina state mental hospitals between March 1st and May 31st, 1994. The main outcome measures are the HIV seroprevalence, demographic and diagnostic features, and clinician assessment of the likelihood of HIV infection. The results of the study find that of 2159 study subjects, 35 persons (1.6%) were infected with HIV; of these, 14 (40%) were not previously known to be infected. All 35 HIV infections occurred in persons aged 13-59 years. Within this age group, infection rates were significantly higher for Blacks, males, persons who had a diagnosis of organic brain disease, and persons who had multiple psychiatric diagnoses. However, testing strategies that targeted any of the higher risk groups were insensitive. The rate of HIV infection for persons judged by the admitting clinician to have a high or intermediate likelihood of HIV infection was 26.4 times higher than the rate for those judged to have a low likelihood of infection (2.1 vs. 0.1%, 95% confidence intervals: 3.5-201.3). Of the 14 previously undiagnosed HIV-infected persons, 13 were judged by clinicians to have a high or intermediate likelihood of HIV infection. Moreover, 1258 persons were correctly assessed to have a low likelihood of infection. Conclusions from this study are that an HIV counseling and testing strategy targeting persons (in this setting aged 13-59 years) who were judged by clinicians to have a high or intermediate likelihood of infection, would have identified more than 90% of previously undetected infections while substantially reducing the number of negative HIV tests performed.