Effector-independent Representations Guide Sequential Target Selection Biases in Action.

Previous work shows that automatic attention biases toward recently selected target features transfer across action and perception and even across different effectors such as the eyes and hands on a trial-by-trial basis. Although these findings suggest a common neural representation of selection history across effectors, the extent to which information about recently selected target features is encoded in overlapping versus distinct brain regions is unknown. Using fMRI and a priming of pop-out task where participants selected unpredictable, uniquely colored targets among homogeneous distractors via reach or saccade, we show that color priming is driven by shared, effector-independent underlying representations of recent selection history. Consistent with previous work, we found that the intraparietal sulcus (IPS) was commonly activated on trials where target colors were switched relative to those where the colors were repeated; however, the dorsal anterior insula exhibited effector-specific activation related to color priming. Via multivoxel cross-classification analyses, we further demonstrate that fine-grained patterns of activity in both IPS and the medial temporal lobe encode information about selection history in an effector-independent manner, such that ROI-specific models trained on activity patterns during reach selection could predict whether a color was repeated or switched on the current trial during saccade selection and vice versa. Remarkably, model generalization performance in IPS and medial temporal lobe also tracked individual differences in behavioral priming sensitivity across both types of action. These results represent a first step to clarify the neural substrates of experience-driven selection biases in contexts that require the coordination of multiple actions.

Determining the pharmacologic window of bisphosphonates that mitigates severe injury-induced osteoporosis and muscle calcification, while preserving fracture repair.

Following severe injury, biomineralization is disrupted and limited therapeutic options exist to correct these pathologic changes. This study utilized a clinically relevant murine model of polytrauma including a severe injury with concomitant musculoskeletal injuries to identify when bisphosphonate administration can prevent the paradoxical decrease of biomineralization in bone and increased biomineralization in soft tissues, yet not interfere with musculoskeletal repair. INTRODUCTION: Systemic and intrinsic mechanisms in bone and soft tissues help promote biomineralization to the skeleton, while preventing it in soft tissues. However, severe injury can disrupt this homeostatic biomineralization tropism, leading to adverse patient outcomes due to a paradoxical decrease of biomineralization in bone and increased biomineralization in soft tissues. There remains a need for therapeutics that restore the natural tropism of biomineralization in severely injured patients. Bisphosphonates can elicit potent effects on biomineralization, though with variable impact on musculoskeletal repair. Thus, a critical clinical question remains as to the optimal time to initiate bisphosphonate therapy in patients following a polytrauma, in which bone and muscle are injured in combination with a severe injury, such as a burn. METHODS: To test the hypothesis that the dichotomous effects of bisphosphonates are dependent upon the time of administration relative to the ongoing biomineralization in reparative bone and soft tissues, this study utilized murine models of isolated injury or polytrauma with a severe injury, in conjunction with sensitive, longitudinal measure of musculoskeletal repair. RESULTS: This study demonstrated that if administered at the time of injury, bisphosphonates prevented severe injury-induced bone loss and soft tissue calcification, but did not interfere with bone repair or remodeling. However, if administered between 7 and 21 days post-injury, bisphosphonates temporally and spatially localized to sites of active biomineralization, leading to impaired fracture callus remodeling and permanence of soft tissue calcification. CONCLUSION: There is a specific pharmacologic window following polytrauma that bisphosphonates can prevent the consequences of dysregulated biomineralization, yet not impair musculoskeletal regeneration.

Re-assessing the importance of linear type traits in predicting genetic merit for survival in an aging Holstein-Friesian dairy cow population.

The cumulative improvement achieved in the genetic merit for reproductive performance in dairy populations will likely improve dairy cow longevity; therefore, it is time to reassess whether linear type traits are still suitable predictors of survival in an aging dairy cow population. The objective of the present study was therefore to estimate the genetic correlations between linear type traits and survival from one parity to the next and, in doing so, evaluate if those genetic correlations change with advancing parity. After edits, 152,894 lactation survival records (first to ninth parity) were available from 52,447 Holstein-Friesian cows, along with linear type trait records from 52,121 Holstein-Friesian cows. A series of bivariate random regression models were used to estimate the genetic covariances between survival in different parities and each linear type trait. Heritability estimates for survival per parity ranged from 0.02 (SE = 0.004; first parity) to 0.05 (SE = 0.01; ninth parity). Pairwise genetic correlations between survival among different parities varied from 0.42 (first and ninth parity) to 1.00 (eighth to ninth parity), with the strength of these genetic correlations being inversely related to the interval between the compared parities. The genetic correlations between survival and the individual linear type traits varied across parities for 9 of the 20 linear type traits examined, but the correlations with only 3 of these linear type traits strengthened as the cows aged; these 3 traits were rear udder height, teat length, and udder depth. Given that linear type traits are frequently scored in first parity and are genetically correlated with survival in older parities, they may be suitable early predictors of survival, especially for later parity cows. Additionally, the direction of the genetic correlations between survival and rear udder height, teat length, and udder depth did not change between parities; hence, selection for survival in older parities using these linear type traits should not hinder genetic improvement for survival in younger parities.

Exploiting genetic variability in the trajectory of lactation yield and somatic cell score with each progressing parity.

The inclusion of reproductive performance in dairy cow breeding schemes has resulted in a cumulative improvement in genetic merit for reproductive performance; this improvement should manifest in longer productive lives through a reduced requirement for involuntary culling. Nonetheless, the average length of dairy cow productive life has not changed in most populations, suggesting that risk factors for culling, especially in older cows, are possibly more associated with lower yield or high somatic cell score (SCS) than compromised reproductive performance. The objective of the present study was to understand the dynamics of lactation yields and SCS in dairy cows across parities and, in doing so, quantify the potential to alter this trajectory through breeding. After edits, 3,470,520 305-d milk, fat, and protein yields, as well as milk fat and protein percentage and somatic cell count records from 1,162,473 dairy cows were available for analysis. Random regression animal models were used to identify the parity in which individual cows reached their maximum lactation yields, and highest average milk composition and SCS; also estimated from these models were the (co)variance components for yield, composition, and SCS per parity across parities. Estimated breeding values for all traits per parity were calculated for cows reaching ≥fifth parity. Of the cows included in the analyses, 91.0%, 92.2%, and 83.4% reached maximum milk, fat, and protein yield in fifth parity, respectively. Conversely, 95.9% of cows reached their highest average fat percentage in first parity and 62.9% of cows reached their highest average protein percentage in third parity. In contrast to both milk yield and composition traits, 98.4% of cows reached their highest average SCS in eighth parity. Individual parity estimates of heritability for milk yield traits, milk composition, and SCS ranged from 0.28 to 0.44, 0.47 to 0.69, and 0.13 to 0.23, respectively. The strength of the genetic correlations per trait among parities was inversely related to the interval between the parities compared; the weakest genetic correlation was 0.67 (standard error = 0.02) between milk yield in parities 1 and 8. Eigenvalues and eigenfunctions of the additive genetic covariance matrices for all investigated traits revealed potential to alter the trajectory of parity profiles for milk yield, milk composition, and SCS. This was further demonstrated when evaluating the trajectories of animal estimated breeding values per parity.

Vancomycin-Resistant Enterococci in Patients Attending for Colonoscopy: An Estimate of Community Prevalence.

Aims Ireland has the highest vancomycin-resistant Enterococcus faecium (VRE) bloodstream infection prevalence in Europe. Two patterns of VRE carriage are recognised. European, with widespread community prevalence and North American, where carriage is predominantly nosocomial. It is unclear which pattern is dominant in Ireland. This uncertainty limits infection control measures. This study sought to explore this issue via a cross sectional point prevalence study. Methods Asymptomatic community volunteers, represented by patients undergoing elective outpatient colonoscopy testing, were opportunistically screened for VRE. Demographic and risk factor data were collected via a patient survey. Rectal swabs were collected before colonoscopy and VRE was identified using the VITEK MS system. Results 102 patients were cultured. A single patient tested positive, representing a prevalence rate of 0.98% (95% CI <0.01-5.8%). This patient demonstrated traditional risk factors, suggesting nosocomial rather than community acquisition. 94% (N=94) of patients had no knowledge of VRE, while 83% (N=83) had low levels of concern regarding hospital acquired infections. Conclusion There is a low incidence of VRE in the Irish community setting, in contrast to other European Countries, suggesting asymptomatic community colonization is not responsible for the high rates of VRE seen in Ireland. Wider screening or atypical infection control measures would not be supported by this data.

The Future of Antifungal Drug Therapy: Novel Compounds and Targets.

Fungal infections are a universal problem and are routinely associated with high morbidity and mortality rates in immunocompromised patients. Existing therapies comprise five different classes of antifungal agents, four of which target the synthesis of ergosterol and cell wall glucans. However, the currently available antifungals have many limitations, including poor oral bioavailability, narrow therapeutic indices, and emerging drug resistance resulting from their use, thus making it essential to investigate the development of novel drugs which can overcome these limitations and add to the antifungal armamentarium. Advances have been made in antifungal drug discovery research and development over the past few years as evidenced by the presence of several new compounds currently in various stages of development. In the following minireview, we provide a comprehensive summary of compounds aimed at one or more novel molecular targets. We also briefly describe potential pathways relevant for fungal pathogenesis that can be considered for drug development in the near future.

Contribution of genetic variability to phenotypic differences in on-farm efficiency metrics of dairy cows based on body weight and milk solids yield.

Milk solids per kilogram of body weight (BW) is growing in popularity as a measure of dairy cow lactation efficiency. Little is known on the extent of genetic variability that exist in this trait but also the direction and strength of genetic correlations with other performance traits. Such genetic correlations are important to know if producers are to consider actively selecting cows excelling in milk solids per kilogram of BW. The objective of the present study was to use a large data set of commercial Irish dairy cows to quantify the extent of genetic variability in milk solids per kilogram of BW and related traits but also their genetic and phenotypic inter-relationships. Mid-lactation BW and body condition score (BCS), along with 305-d milk solids yield (i.e., fat plus protein yield) were available on 12,413 lactations from 11,062 cows in 85 different commercial dairy herds. (Co)variance components were estimated using repeatability animal linear mixed models. The genetic correlation between milk solids and body weight was only 0.05, which when coupled with the observed large genetic variability in both traits, indicate massive potential to select for both traits in opposite directions. The genetic correlations between both milk solids and BW with BCS; however, need to be considered in any breeding strategy. The genetic standard deviation, heritability, and repeatability of milk solids per kilogram of BW was 0.08, 0.37, and 0.57, respectively. The genetic correlation between milk solids per kilogram of BW with milk solids, BW, and BCS was 0.62, -0.75, and -0.41, respectively. Therefore, based on genetic regression, each increase of 0.10 units in genetic merit for milk solids per kilogram of BW is expected to result in, on average, an increase in 16.1 kg 305-d milk solids yield, a reduction of 25.6 kg of BW and a reduction of 0.05 BCS units (scale of 1-5 where 1 is emaciated). The genetic standard deviation (heritability) for 305-d milk solids yield adjusted phenotypically to a common BW was 27.3 kg (0.22). The genetic correlation between this adjusted milk solids trait with milk solids, BW, and BCS was 0.91, -0.12, and -0.26, respectively. Once also adjusted phenotypically to a common BCS, the genetic standard deviation (heritability) for milk solids adjusted phenotypically to a common BW was 26.8 kg (0.22) where the genetic correlation with milk solids, BW and BCS was 0.91, -0.21, and -0.07, respectively. The genetic standard deviation (heritability) of BW adjusted phenotypically for differences in milk solids was 35.3 kg (0.61), which reduced to 33.2 kg when also phenotypically adjusted for differences in BCS. Results suggest considerable opportunity exists to change milk solids yield independent of BW, and vice versa. The opportunity is reduced slightly once also corrected for differences in BCS. Inter-animal BCS differences should be considered if selection on such metrics is contemplated.

Perceived group size is determined by the centroids of the component elements.

To accomplish the deceptively simple task of perceiving the size of objects in the visual scene, the visual system combines information about the retinal size of the object with several other cues, including perceived distance, relative size, and prior knowledge. When local component elements are perceptually grouped to form objects, the task is further complicated because a grouped object does not have a continuous contour from which retinal size can be estimated. Here, we investigate how the visual system solves this problem and makes it possible for observers to judge the size of perceptually grouped objects. We systematically vary the shape and orientation of the component elements in a two-alternative forced-choice task and find that the perceived size of the array of component objects can be almost perfectly predicted from the distance between the centroids of the component elements and the center of the array. This is true whether the global contour forms a circle or a square. When elements were positioned such that the centroids along the global contour were at different distances from the center, perceived size was based on the average distance. These results indicate that perceived size does not depend on the size of individual elements, and that smooth contours formed by the outer edges of the component elements are not used to estimate size. The current study adds to a growing literature highlighting the importance of centroids in visual perception and may have implications for how size is estimated for ensembles of different objects.

Preclinical Evaluation of Acylhydrazone SB-AF-1002 as a Novel Broad-Spectrum Antifungal Agent.

The incidence of invasive fungal infections is rising due to the increase in susceptible populations. Current clinically available drugs have therapeutic limitations due to toxicity, a narrow spectrum of activity, and, more importantly, the consistent rise of fungal species that are intrinsically resistant or that develop resistance due to prolonged therapy. Thus, there is an urgent need for new broad-spectrum antifungal agents with low toxicity and a novel mechanism of action. We previously reported a new class of potent antifungal compounds, acylhydrazones, that target the fungal sphingolipid pathway. Based upon our initial lead molecules, (E)-N'-(5-bromo-2-hydroxybenzylidene)-2-methylbenzohydrazide and D13, we performed a structure-activity relationship study, synthesizing ca. 300 new compounds. Of these, 5 compounds were identified to be the most promising for further studies, based on their broad-spectrum activity and low toxicity in mammalian cells lines. Among these top 5 lead compounds, we report here the impressive in vivo activity of 2,4-dibromo-N'-(5-bromo-2-hydroxybenzylidene)benzohydrazide (SB-AF-1002) in several models of systemic fungal infection. Our data show that SB-AF-1002 is efficacious and outperforms current standard-of-care drugs in models of invasive fungal infections, such as cryptococcosis, candidiasis, and aspergillosis. Specifically, animals treated with SB-AF-1002 not only survived the infection but also showed a clearing of fungal cells from key organs. Moreover, SB-AF-1002 was very effective in an aspergillosis model as a prophylactic therapy. SB-AF-1002 also displayed acceptable pharmacokinetic properties in mice, similar to those of the parent compound, D13. These results clearly indicate that our novel acylhydrazones constitute a new class of highly potent and efficacious antifungal agents which warrant further development for the treatment of invasive fungal infections.

Psychosocial, psychiatric and work-related risk factors associated with suicide in Ireland: optimised methodological approach of a case-control psychological autopsy study.

BACKGROUND: Suicide has profound effects on families and communities, but is a statistically rare event. Psychological autopsies using a case-control design allow researchers to examine risk factors for suicide, using a variety of sources to detail the psychological and social characteristics of decedents and to compare them to controls. The Suicide Support and Information System Case Control study (SSIS-ACE) aimed to compare psychosocial, psychiatric and work-related risk factors across three groups of subjects: suicide decedents, patients presenting to hospital with a high-risk self-harm episode, and general practice controls. METHODS: The study design includes two inter-related studies; one main case-control study: comparing suicide cases to general practice (GP) controls, and one comparative study: comparing suicide cases to patients presenting with high-risk self-harm. Consecutive cases of suicide and probable suicide are identified through coroners' registration of deaths in the defined region (Cork City and County, Ireland) and are frequency-matched for age group and gender with GP patient controls recruited from the same GP practice as the deceased. Data sources for suicide cases include coroners' records, interviews with health care professionals and proxy informants; data sources for GP controls and for high-risk self-harm controls include interviews with control, with proxy informants and with health care professionals. Interviews are semi-structured and consist of quantitative and qualitative parts. The quantitative parts include a range of validated questionnaires addressing psychiatric, psychosocial and occupational factors. The study adopts several methodological innovations, including accessing multiple data sources for suicide cases and controls simultaneously, recruiting proxy informants to examine consistency across sources. CONCLUSIONS: The study allows for the investigation of consistency across different data sources and contributes to the methodological advancement of psychological autopsy research. The study will also inform clinical and public health practice. The comparison between suicide cases and controls will allow investigation of risk and protective factors for suicide more generally, while the comparison with high-risk self-harm patients will help to identify the factors associated specifically with a fatal outcome to a self-harm episode. A further enhancement is the particular focus on specific work-related risk factors for suicide.

A mating advice system in dairy cattle incorporating genomic information.

This study investigated the effects of alternative mating programs that incorporate genomic information on expected progeny herd performance and inbreeding, as well as methods to include un-genotyped animals in such mating programs. A total of 54,535 Holstein-Friesian cattle with imputed high-density genotypes (547,650 SNP after edits) were available. First, to quantify the accuracy of imputing un-genotyped animals (often an issue in populations), a sub-population of 729 genotyped animals had their genotypes masked, and their allele dosages were imputed, using linear regression exploiting information on genotyped relatives. The reference population for imputation included all genotyped animals, excluding the 729 selected animals and their sires, dams, and grandsires, and had either (1) their sires' genotypes, (2) their dams' genotypes (3) both their sires' and their dams' genotypes, or (4) both their sires' and maternal grandsires' genotypes introduced into the reference population. The correlations between true genotypes and the imputed allele dosages ranged from 0.58 (sire only) to 0.68 (both sire and dam). A herd of 100 cows was then simulated (1,000 replicates) from the sub-population of 729 imputed animals. The top 10 bulls from the genotyped population, based on their total genetic merit index (TMI) were selected to be used as sires. Three mating allotment methods were investigated: (1) random mating, (2) sequential mating based on maximizing only the expected TMI of the progeny, and (3) linear programming to maximize a generated index constructed to maximize genetic merit and minimize expected progeny inbreeding as well as intra- and inter-progeny variability in genetic merit. Relationships among candidate parents were calculated using either the pedigree relationship matrix or the genomic relationship matrix; the latter was constructed using either the true genotypes of both parents or the true genotypes of the sire plus the imputed allele dosages of the dam. Using the genomic co-ancestry estimates resulted in lower average herd expected genomic inbreeding levels compared with using the pedigree-based co-ancestry estimates. Additionally, if the dams were not genotyped, using their imputed allele dosages also resulted in lower average herd expected inbreeding levels compared with using the pedigree co-ancestry estimates. The inter-progeny coefficient of variation for selected traits, milk and fertility, estimated breeding values were reduced by 12 to 65% using the linear programing method compared with sequential mating.

Transcatheter Mitral Valve-in-Ring Implantation.

Failed surgical mitral valve repair using an annuloplasty ring has traditionally been treated with surgical valve replacement or repair1. For patients at high risk for repeat open heart surgery, placement of a trans-catheter aortic valve (i.e., TAVI valve) within the mitral ring (i.e., Mitral-Valve-in-Ring, MViR) has emerged as a novel alternative treatment strategy2-5 . We describe our experience of a failed mitral valve repair that was successfully treated with a TAVI valve delivered via the trans-septal approach, and summarise the data relating to this emerging treatment strategy.

Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease-causing variants.

The Ashkenazi Jewish (AJ) population has an increased risk for a variety of recessive diseases due to historical founder effects and genetic drift. For some, the disease-causing founder mutations have been identified and well-characterized, but for others, further study is necessary. The purpose of this study is to assess the carrier frequencies of 85 pathogenic variants causative of 29 recessive conditions in the AJ population. Up to 3000 AJ individuals were genotyped by Luminex MagPlex® -TAG™ bead array or Agena Bioscience™ MassARRAY assays. We identified seven conditions with carrier frequencies higher than 1 in 100, nine between 1 in 100 and 1 in 200, and four between 1 in 200 and 1 in 500. Variants in nine conditions had a detected carrier rate of less than 1 in 500 or were not identified in approximately 2000 AJ individuals. We assessed the combined AJ carrier frequency for 18 relatively prevalent diseases to be 1 in 6, and the risk of AJ individuals to be a carrier couple for one of these 18 diseases as 1 in 441. We note additional recessive genetic conditions should be considered for AJ carrier screening panels.

Characteristics of prisoners with intellectual disabilities.

BACKGROUND: Previous studies have found high rates of intellectual disabilities (ID) in prison. However, little is understood about prisoners with ID. This study aimed to identify prisoners with ID and compare their characteristics with prisoners without neurodevelopmental disorders with regard to demographic profile, mental health, suicide risk and offences. METHOD: This was a descriptive, cross-sectional study carried out using face-to-face interviews with 240 participants in a London Category C prison. Standardised tools were used to assess prisoners for ID and mental disorder. RESULTS: The study identified 18 prisoners as having ID. Participants with ID were less likely to be from a black or minority ethnic background, be over 35 years of age or have any qualifications. They were more likely to have been single, homeless or unemployed before coming into prison. Prisoners with ID were significantly more likely to have mental health problems and 25% had thought about suicide in the last month and 63% had attempted suicide in the past. Prisoners with ID were also more likely to be housed in the vulnerable prisoners' wing and significantly more likely to have committed robbery than other prisoners. CONCLUSIONS: The findings confirm the presence of significant numbers of people with ID with high levels of mental illness in a male prison. Services across the CJS are required for this group, specifically, there is a need for raised awareness among those working in prison about ID and improved skills to recognise offenders with ID and address major gaps in current healthcare provision in prison.

The multi-year cumulative effects of alternative stocking rate and grazing management practices on pasture productivity and utilization efficiency.

The production and utilization of increased quantities of high quality pasture is of paramount importance in pasture-based milk production systems. The objective of this study was to evaluate the cumulative effects of alternative integrated grazing strategies, incorporating alternative stocking rate (SR) and grazing severities, on pasture productivity and grazing efficiency over multiple years within farm systems using perennial ryegrass dominant pastures. Three whole-farm SR treatments were compared over 4 complete grazing seasons (2009 to 2012 inclusive): low (2.51 cows/ha; LSR), medium (2.92 cows/ha; MSR), and high (3.28 cows/ha; HSR). Each system had its own farmlet containing 18 paddocks and remained on the same treatment for the duration of the study. Stocking rate had a significant effect on all grazing variables with the exception of soil fertility status and sward density. Increased SR resulted in increased total annual net pasture accumulation, improved sward nutritive value, and increased grazed pasture utilization. Total annual net pasture accumulation was greatest in HSR [15,410kg of dry matter (DM)/ha], intermediate for MSR (14,992kg of DM/ha), and least for LSR (14,479kg of DM/ha) during the 4-yr study period. A linear effect of SR on net pasture accumulation was detected with an increase in net pasture accumulation of 1,164.4 (SE=432.7) kg of DM/ha for each 1 cow/ha increase in SR. Pregrazing pasture mass and height and postgrazing residual pasture mass and height were greatest for LSR, intermediate for the MSR, and lowest for the HSR. In comparison with the LSR, the imposition of a consistently increased grazing severity coupled with increased whole farm SR in MSR and HSR treatments arrested the decline in sward nutritive value, typically observed during mid-season. Incorporating the individual beneficial effects of SR on pasture accumulation, nutritive value, and utilization efficiency, total proportional energy (unité fourragère lait) utilization per hectare increased significantly with increasing SR (+0.026 and +0.081 for MSR and HSR, respectively). These results quantify the significant effect of grazing management practices on the feed production capability of modern perennial ryegrass pastures for intensive grazing dairy production systems. Furthermore, these results highlight the importance of consistently imposing grazing treatments over multiple years, and within integrated whole farm systems, to accurately assess the longer term effects of alternate grazing management practices on pasture productivity.

Characteristics of prisoners with neurodevelopmental disorders and difficulties.

BACKGROUND: Previous studies have found high rates of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) within the criminal justice system (CJS). However, little is understood about prisoners with neurodevelopmental disorders and difficulties (NDD) or their needs. This study aimed to identify prisoners with NDD and compare their characteristics with prisoners without NDD on a range of socio-demographic and social functioning measures. METHOD: This was a descriptive, cross-sectional study carried out using face-to-face interviews with 240 participants in a London Category C prison. Standardised tools were used to assess prisoners for ADHD, ASD and ID. RESULTS: The study identified 87 prisoners who screened positive for one or more type of NDD. Participants with NDD were significantly younger and more likely to be single [(odds ratio) OR = 2.1], homeless (OR = 3.4) or unemployed (OR = 2.6) before they came into prison. They also had poorer educational achievements that those without NDD. Over 80% of those with NDD had a previous conviction or imprisonment. CONCLUSIONS: The findings confirm the presence of significant numbers of people with NDD in a male prison. Services across the CJS are required for this group; specifically, there is a need for raised awareness among those working in the CJS to improve the recognition of offenders with NDD. Services in the community need to work with individuals with NDD who are at risk of offending, targeting those who are homeless, unemployed and have poor employment opportunities.

Global attention facilitates the planning, but not execution of goal-directed reaches.

In daily life, humans interact with multiple objects in complex environments. A large body of literature demonstrates that target selection is biased toward recently attended features, such that reaches are faster and trajectory curvature is reduced when target features (i.e., color) are repeated (priming of pop-out). In the real world, however, objects are comprised of several features-some of which may be more suitable for action than others. When fetching a mug from the cupboard, for example, attention not only has to be allocated to the object, but also the handle. To date, no study has investigated the impact of hierarchical feature organization on target selection for action. Here, we employed a color-oddity search task in which targets were Pac-men (i.e., a circle with a triangle cut out) oriented to be either consistent or inconsistent with the percept of a global Kanizsa triangle. We found that reaches were initiated faster when a task-irrelevant illusory figure was present independent of color repetition. Additionally, consistent with priming of pop-out, both reach planning and execution were facilitated when local target colors were repeated, regardless of whether a global figure was present. We also demonstrated that figures defined by illusory, but not real contours, afforded an early target selection benefit. In sum, these findings suggest that when local targets are perceptually grouped to form an illusory surface, attention quickly spreads across the global figure and facilitates the early stage of reach planning, but not execution. In contrast, local color priming is evident throughout goal-directed reaching.

Cyclodextrin mediated delivery of NF-κB and SRF siRNA reduces the invasion potential of prostate cancer cells in vitro.

Prostate cancer is the most common cancer in men of the western world. To date, no effective treatment exists for metastatic prostate cancer and consequently, there is an urgent need to develop new and improved therapeutics. In recent years, the therapeutic potential of RNA interference (RNAi) has been extensively explored in a wide range of diseases including prostate cancer using numerous gene delivery vectors. The aims of this study were to investigate the ability of a non-viral modified cyclodextrin (CD) vector to deliver siRNA to the highly metastatic PC-3 prostate cancer cell line, to quantify the resulting knockdown of the two target genes (RelA and SRF) and to study the effects of the silencing on metastasis. Data from a Matrigel in vitro invasion assay indicated that the silencing of the target genes achieved by the CD vector resulted in significant reductions (P=0.0001) in the metastatic potential of these cells. As the silencing of these target genes was shown not to have a negative impact on cell viability, we hypothesise that the mechanism of invasion inhibition is due, in part, to the significant reduction observed (P⩽0.0001) in the level of pro-inflammatory cytokine, MMP9, which is known to be implicated in the metastasis of prostate cancer.

Extrastriate Visual Areas Integrate Form Features over Space and Time to Construct Representations of Stationary and Rigidly Rotating Objects.

When an object moves behind a bush, for example, its visible fragments are revealed at different times and locations across the visual field. Nonetheless, a whole moving object is perceived. Unlike traditional modal and amodal completion mechanisms known to support spatial form integration when all parts of a stimulus are simultaneously visible, relatively little is known about the neural substrates of the spatiotemporal form integration (STFI) processes involved in generating coherent object representations from a succession visible fragments. We used fMRI to identify brain regions involved in two mechanisms supporting the representation of stationary and rigidly rotating objects whose form features are shown in succession: STFI and position updating. STFI allows past and present form cues to be integrated over space and time into a coherent object even when the object is not visible in any given frame. STFI can occur whether or not the object is moving. Position updating allows us to perceive a moving object, whether rigidly rotating or translating, even when its form features are revealed at different times and locations in space. Our results suggest that STFI is mediated by visual regions beyond V1 and V2. Moreover, although widespread cortical activation has been observed for other motion percepts derived solely from form-based analyses [Tse, P. U. Neural correlates of transformational apparent motion. Neuroimage, 31, 766-773, 2006; Krekelberg, B., Vatakis, A., & Kourtzi, Z. Implied motion from form in the human visual cortex. Journal of Neurophysiology, 94, 4373-4386, 2005], increased responses for the position updating that lead to rigidly rotating object representations were only observed in visual areas KO and possibly hMT+, indicating that this is a distinct and highly specialized type of processing.

Scaling up self-assembly: bottom-up approaches to macroscopic particle organization.

This review presents an overview of recent work in the field of non-Brownian particle self-assembly. Compared to nanoparticles that naturally self-assemble due to Brownian motion, larger, non-Brownian particles (d > 6 µm) are less prone to autonomously organize into crystalline arrays. The tendency for particle systems to experience immobilization and kinetic arrest grows with particle radius. In order to overcome this kinetic limitation, some type of external driver must be applied to act as an artificial "thermalizing force" upon non-Brownian particles, inducing particle motion and subsequent crystallization. Many groups have explored the use of various agitation methods to overcome the natural barriers preventing self-assembly to which non-Brownian particles are susceptible. The ability to create materials from a bottom-up approach with these characteristics would allow for precise control over their pore structure (size and distribution) and surface properties (topography, functionalization and area), resulting in improved regulation of key characteristics such as mechanical strength, diffusive properties, and possibly even photonic properties. This review will highlight these approaches, as well as discuss the potential impact of bottom-up macroscale particle assembly. The applications of such technology range from customizable and autonomously self-assembled niche microenvironments for drug delivery and tissue engineering to new acoustic dampening, battery, and filtration materials, among others. Additionally, crystals made from non-Brownian particles resemble naturally derived materials such as opals, zeolites, and biological tissue (i.e. bone, cartilage and lung), due to their high surface area, pore distribution, and tunable (multilevel) hierarchy.