The detection of multiple global directions: Capacity limits with spatially segregated and transparent-motion signals

An important constraint on motion processing is the maximum number of directions that can be perceived at the same time. When transparent-motion stimuli are constructed based solely on direction differences, prior studies demonstrate that no more than two directions are seen simultaneously. However, this limit has been extended to three when signal directions drive independent speed- or disparity-tuned global-motion systems. The present study sought to determine whether this three-direction capacity reflects the specific mechanisms of transparent-motion detection or a more general restriction on global-motion processing. Using both transparent and spatially segregated stimuli, observers indicated which of the two intervals contained the most directions, with simultaneous processing ensured through brief durations and n vs. n + 1 signal comparisons. When spatially segregated directions were interleaved in patches, no more than two were seen, as with direction-defined transparent motion. In contrast, separating these directions into distinct spatial regions allowed the detection of up to three. Signal-detection thresholds did not vary across these signal arrangements, suggesting that the two-direction capacity results from signal-to-noise pooling across the entire stimulus, with the higher capacity for spatially distinct directions arising from independent pooling within each region. Together, these results provide further evidence for an upper capacity of three directions within the global-motion stage

Management of functional neurological disorder.

Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. These symptoms are varied and include abnormal control of movement, episodes of altered awareness resembling epileptic seizures and abnormal sensation and are often comorbid with chronic pain, fatigue and cognitive symptoms. There is increasing evidence for the role of neurologists in both the assessment and management of FND. The aim of this review is to discuss strategies for the management of FND by focusing on the diagnostic discussion and general principles, as well as specific treatment strategies for various FND symptoms, highlighting the role of the neurologist and proposing a structure for an interdisciplinary FND service

The importance of metagenomic surveys to microbial ecology: or why Darwin would have been a metagenomic scientist

Scientific discovery is incremental. The Merriam-Webster definition of 'Scientific Method' is "principles and procedures for the systematic pursuit of knowledge involving the recognition and formulation of a problem, the collection of data through observation and experiment, and the formulation and testing of hypotheses". Scientists are taught to be excellent observers, as observations create questions, which in turn generate hypotheses. After centuries of science we tend to assume that we have enough observations to drive science, and enable the small steps and giant leaps which lead to theories and subsequent testable hypotheses. One excellent example of this is Charles Darwin's Voyage of the Beagle, which was essentially an opportunistic survey of biodiversity. Today, obtaining funding for even small-scale surveys of life on Earth is difficult; but few argue the importance of the theory that was generated by Darwin from his observations made during this epic journey. However, these observations, even combined with the parallel work of Alfred Russell Wallace at around the same time have still not generated an indisputable 'law of biology'. The fact that evolution remains a 'theory', at least to the general public, suggests that surveys for new data need to be taken to a new level

Contrasting impacts of land use change on phylogenetic and functional diversity of tropical forest birds

1. Biodiversity conservation strategies increasingly target maintaining evolutionary history and the resilience of ecosystem function, not just species richness (SR). This has led to the emergence of two metrics commonly proposed as tools for decision making: phylogenetic diversity (PD) and functional diversity (FD). Yet the extent to which they are interchangeable remains poorly understood. 2. We explore shifts in and relationships between FD and PD of bird communities across a disturbance gradient in Borneo, from old-growth tropical forest to oil palm plantation. 3. We show a marked decline in PD, and an increase in phylogenetic mean nearest taxon distance (MNTD) from forest to oil palm, in line with declining SR across the gradient. However, phylogenetic mean pairwise distance (MPD) is constrained by forest logging more than by conversion to oil palm, taking account of SR. 4. The decline in FD across the gradient is less severe than in PD, with all metrics indicating relatively high trait diversity in oil palm despite low SR, although functional redundancy is much reduced. Accounting for SR, levels of functional over- or under-dispersion of bird communities are strongly coupled to habitat disturbance level rather than to any equivalent phylogenetic metric. 5. Policy Implications. We suggest that while phylogenetic diversity (PD) is an improvement on species richness as a proxy for functional diversity (FD), conservation decisions based on PD alone cannot reliably safeguard maximal FD. Thus, PD and FD are related but still complementary. Priority setting exercises should use these metrics in combination to identify conservation targets

Age of the Laschamp excursion determined by U-Th dating of a speleothem geomagnetic record from North America

The Laschamp geomagnetic excursion was the first short-lived polarity event recognized and described in the paleomagnetic record, and to date remains the most studied geomagnetic event of its kind. In addition to its geophysical significance, the Laschamp is an important global geochronologic marker. The Laschamp excursion occurred around the time of the demise of Homo neanderthalensis, in conjunction with high-amplitude, rapid climatic oscillations leading into the Last Glacial Maximum, and coeval with a major supervolcano eruption in the Mediterranean. Thus, precise determination of the timing and duration of the Laschamp excursion would help in elucidating major scientific questions situated at the intersection of geology, paleoclimatology, and anthropology. Here we present a North American speleothem geomagnetic record of the Laschamp excursion that is directly dated using a combination of high-precision 230Th dates and annual layer counting using confocal microscopy. We have determined a maximum excursion duration that spans the interval 42,250-39,700 yr BP, and an age of 41,100 ± 350 yr BP for the main phase of the excursion, during which the virtual geomagnetic pole was situated at the southernmost latitude in the record. Our chronology provides the first age bracketing of the Laschamp excursion using radioisotopic dating, and improves on previous age determinations based on 40Ar/39Ar dating of lava flows, and orbitally-tuned sedimentary and ice-core records.This project was funded by NSF-EAR grant 1316385, a University of Minnesota McKnight Land Grant Professorship to JMF, and ERC grant 320750. Confocal microscopy was performed at the University of Minnesota Imaging Centers. We are grateful to John Geissman, Brad Singer, and James Channell for their constructive reviews. This is Institute for Rock Magnetism contribution 1506.This is the author accepted manuscript. The final version is available from the Geological Society of America via http://dx.doi.org/10.1130/G37490.

Phosphorylation of the androgen receptor is associated with reduced survival in hormonerefractory prostate cancer patients

Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (<i>P</i>=0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (<i>P</i>=0.014), and an increase in expression of pAkt<sup>473</sup> and pAR<sup>210</sup> were associated with decreased disease-specific survival (<i>P</i>=0.0019 and 0.0015, respectively). Protein expression of pAkt<sup>473</sup> and pAR<sup>210</sup> also strongly correlated (<i>P</i><0.001, c.c.=0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

The depression in visual impairment trial (DEPVIT): trial design and protocol

<b>Background</b> The prevalence of depression in people with a visual disability is high but screening for depression and referral for treatment is not yet an integral part of visual rehabilitation service provision. One reason for this may be that there is no good evidence about the effectiveness of treatments in this patient group. This study is the first to evaluate the effect of depression treatments on people with a visual impairment and co morbid depression.<p></p> <b>Methods/design</b> The study is an exploratory, multicentre, individually randomised waiting list controlled trial. Participants will be randomised to receive Problem Solving Therapy (PST), a ‘referral to the GP’ requesting treatment according to the NICE’s ‘stepped care’ recommendations or the waiting list arm of the trial. The primary outcome measure is change (from randomisation) in depressive symptoms as measured by the Beck’s Depression Inventory (BDI-II) at 6 months. Secondary outcomes include change in depressive symptoms at 3 months, change in visual function as measured with the near vision subscale of the VFQ-48 and 7 item NEI-VFQ at 3 and 6 months, change in generic health related quality of life (EQ5D), the costs associated with PST, estimates of incremental cost effectiveness, and recruitment rate estimation.<p></p> <b>Discussion</b> Depression is prevalent in people with disabling visual impairment. This exploratory study will establish depression screening and referral for treatment in visual rehabilitation clinics in the UK. It will be the first to explore the efficacy of PST and the effectiveness of NICE’s ‘stepped care’ approach to the treatment of depression in people with a visual impairment.<p></p&gt

Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: Results of the randomized, placebocontrolled PALACE 4 trial

Objectives. The PALACE 4 trial evaluated apremilast monotherapy in patients with active PsA who were DMARD-naive. Methods. Eligible patients were randomized (1:1:1) to placebo, apremilast 20mg twice a day or apremilast 30mg twice a day. At week 16 or 24, placebo patients were rerandomized to apremilast. Double-blind apremilast treatment continued to week 52, with extension up to 4 years. The primary endpoint was the proportion of patients achieving ≥20% improvement in ACR response criteria (ACR20) at week 16; secondary endpoints included the mean change in the HAQ Disability Index (HAQ-DI) score at week 16. Results. A total of 527 patients with mean disease duration of 3.4 years and high disease activity were randomized and received treatment. More apremilast patients achieved ACR20 response at week 16 [placebo, 15.9%; 20 mg, 28.0% (P = 0.0062); 30 mg, 30.7% (P = 0.0010)]. The mean HAQ-DI improvements were -0.17 (20 mg; P = 0.0008) and -0.21 (30 mg; P<0.0001) vs 0.03 (placebo). Both apremilast doses showed significant ACR50 responses vs placebo at week 16 and improvements in secondary efficacy measures (swollen/tender joint counts) and psoriasis assessments, with sustained improvements through week 52. Common adverse events (AEs) over 52 weeks were diarrhoea, nausea, headache and upper respiratory tract infection; most events were mild or moderate. Serious AEs and AEs leading to discontinuation were comparable between groups. Laboratory abnormalities were infrequent and transient. Conclusions. In DMARD-naive patients, apremilast monotherapy improved PsA signs/symptoms over 52 weeks and was generally well tolerated