Continuous growth of proximal tubular kidney epithelial cells in hormone-supplemented serum-free medium.

An epithelial cell line from pig kidney (LLC-PK1) with properties of proximal tubular cells can be maintained indefinitely in hormone-supplemented serum-free medium. Continuous growth requires the presence of seven factors: transferrin, insulin, selenium, hydrocortisone, triiodothyronine, vasopressin, and cholesterol. The hormone-defined medium (a) supports growth of LLC-PK1 cells at a rate of approaching that observed in serum-supplemented medium; (b) allows vectorial transepithelial salt and fluid transport as measured by hemicyst formation; and (c) influences cell morphology. The vasopressin dependency for growth and morphology can be partially replaced by isobutylmethylxanthine or dibutyryl cyclic AMP. The medium has been used to isolate rabbit proximal tubular kidney epithelial cells free of fibroblasts

Change detection in children with autism: an auditory event-related fMRI study

Autism involves impairments in communication and social interaction, as well as high levels of repetitive, stereotypic and ritualistic behaviours, and extreme resistance to change. This latter dimension, whilst required for a diagnosis, has received less research attention. We hypothesise that this extreme resistance to change in autism is rooted in atypical processing of unexpected stimuli. We tested this using auditory event-related fMRI to determine regional brain activity associated with passive detection of infrequently occurring frequency-deviant and complex novel sounds in a no-task condition. Participants were twelve 10 to 15-year-old children with autism, and a group of 12 age- and sex-matched healthy controls

Pricing Multi-Unit Markets

We study the power and limitations of posted prices in multi-unit markets, where agents arrive sequentially in an arbitrary order. We prove upper and lower bounds on the largest fraction of the optimal social welfare that can be guaranteed with posted prices, under a range of assumptions about the designer's information and agents' valuations. Our results provide insights about the relative power of uniform and non-uniform prices, the relative difficulty of different valuation classes, and the implications of different informational assumptions. Among other results, we prove constant-factor guarantees for agents with (symmetric) subadditive valuations, even in an incomplete-information setting and with uniform prices

From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition.

Growing evidence points toward a critical role for early (prenatal) atypical neurodevelopmental processes in the aetiology of autism spectrum condition (ASC). One such process that could impact early neural development is inflammation. We review the evidence for atypical expression of molecular markers in the amniotic fluid, serum, cerebrospinal fluid (CSF), and the brain parenchyma that suggest a role for inflammation in the emergence of ASC. This is complemented with a number of neuroimaging and neuropathological studies describing microglial activation. Implications for treatment are discussed.Medical Research Council, Autism Research Trust, William Binks Autism Neuroscience FellowshipThis is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13229-016-0068-

Pupil dilation as an index of preferred mutual gaze duration

Most animals look at each other to signal threat or interest. In humans, this social interaction is usually punctuated with brief periods of mutual eye contact. Deviations from this pattern of gazing behaviour generally make us feel uncomfortable and are a defining characteristic of clinical conditions such as autism or schizophrenia, yet it is unclear what constitutes normal eye contact. Here, we measured, across a wide range of ages, cultures and personality types, the period of direct gaze that feels comfortable and examined whether autonomic factors linked to arousal were indicative of people’s preferred amount of eye contact. Surprisingly, we find that preferred period of gaze duration is not dependent on fundamental characteristics such as gender, personality traits or attractiveness. However, we do find that subtle pupillary changes, indicative of physiological arousal, correlate with the amount of eye contact people find comfortable. Specifically, people preferring longer durations of eye contact display faster increases in pupil size when viewing another person than those preferring shorter durations. These results reveal that a person’s preferred duration of eye contact is signalled by physiological indices (pupil dilation) beyond volitional control that may play a modulatory role in gaze behaviour

The Milliarcsecond Structure of Radio Galaxies and Quasars

Hybrid maps of the nuclei of radio galaxies and quasars show a variety of morphologies. Among compact sources, two structures are common: an asymmetric, “core-jet” morphology (eg, 3C 273), and an “equal double” morphology with two separated, similar components (eg, CTD 93). The nuclei of extended, double radio galaxies generally have a core-jet morphology with the jet directed toward one of the outer components

An innovative quality improvement curriculum for third-year medical students

Background: Competence in quality improvement (QI) is a priority for medical students. We describe a self-directed QI skills curriculum for medical students in a 1-year longitudinal integrated third-year clerkship: an ideal context to learn and practice QI. Methods: Two groups of four students identified a quality gap, described existing efforts to address the gap, made quantifying measures, and proposed a QI intervention. The program was assessed with knowledge and attitude surveys and a validated tool for rating trainee QI proposals. Reaction to the curriculum was assessed by survey and focus group. Results: Knowledge of QI concepts did not improve (mean knowledge score±SD): pre: 5.9±1.5 vs. post: 6.6±1.3, p=0.20. There were significant improvements in attitudes (mean topic attitude score±SD) toward the value of QI (pre: 9.9±1.8 vs. post: 12.6±1.9, p=0.03) and confidence in QI skills (pre: 13.4±2.8 vs. post: 16.1±3.0, p=0.05). Proposals lacked sufficient analysis of interventions and evaluation plans. Reaction was mixed, including appreciation for the experience and frustration with finding appropriate mentorship. Conclusion: Clinical-year students were able to conduct a self-directed QI project. Lack of improvement in QI knowledge suggests that self-directed learning in this domain may be insufficient without targeted didactics. Higher order skills such as developing measurement plans would benefit from explicit instruction and mentorship. Lessons from this experience will allow educators to better target QI curricula to medical students in the clinical years

Music Perception in Dementia.

Despite much recent interest in music and dementia, music perception has not been widely studied across dementia syndromes using an information processing approach. Here we addressed this issue in a cohort of 30 patients representing major dementia syndromes of typical Alzheimer's disease (AD, n = 16), logopenic aphasia (LPA, an Alzheimer variant syndrome; n = 5), and progressive nonfluent aphasia (PNFA; n = 9) in relation to 19 healthy age-matched individuals. We designed a novel neuropsychological battery to assess perception of musical patterns in the dimensions of pitch and temporal information (requiring detection of notes that deviated from the established pattern based on local or global sequence features) and musical scene analysis (requiring detection of a familiar tune within polyphonic harmony). Performance on these tests was referenced to generic auditory (timbral) deviance detection and recognition of familiar tunes and adjusted for general auditory working memory performance. Relative to healthy controls, patients with AD and LPA had group-level deficits of global pitch (melody contour) processing while patients with PNFA as a group had deficits of local (interval) as well as global pitch processing. There was substantial individual variation within syndromic groups. Taking working memory performance into account, no specific deficits of musical temporal processing, timbre processing, musical scene analysis, or tune recognition were identified. The findings suggest that particular aspects of music perception such as pitch pattern analysis may open a window on the processing of information streams in major dementia syndromes. The potential selectivity of musical deficits for particular dementia syndromes and particular dimensions of processing warrants further systematic investigation

Oxygen and Carbon Dioxide Rhythms Are Circadian Clock Controlled and Differentially Directed by Behavioral Signals

This is the author accepted manuscript. The final version is available from Elsevier (Cell Press).Daily rhythms in animal physiology are driven by endogenous circadian clocks in part through rest-activity and feeding-fasting cycles. Here, we examined principles that govern daily respiration. We monitored oxygen consumption and carbon dioxide release, as well as tissue oxygenation in freely moving animals to specifically dissect the role of circadian clocks and feeding time on daily respiration. We found that daily rhythms in oxygen and carbon dioxide are clock controlled and that time-restricted feeding restores their rhythmicity in clock-deficient mice. Remarkably, day-time feeding dissociated oxygen rhythms from carbon dioxide oscillations, whereby oxygen followed activity, and carbon dioxide was shifted and aligned with food intake. In addition, changes in carbon dioxide levels altered clock gene expression and phase shifted the clock. Collectively, our findings indicate that oxygen and carbon dioxide rhythms are clock controlled and feeding regulated and support a potential role for carbon dioxide in phase resetting peripheral clocks upon feeding.British Heart FoundationEuropean Research CouncilEuropean Union, Seventh Framework Program, Marie Curie Action

Recurring types of variability and transitions in the ∼620 kyr record of climate change from the Chew Bahir basin, southern Ethiopia

The Chew Bahir Drilling Project (CBDP) aims to test possible linkages between climate and hominin evolution in Africa through the analysis of sediment cores that have recorded environmental changes in the Chew Bahir basin (CHB). In this statistical project we used recurrence plots (RPs) together with a recurrence quantification analysis (RQA) to distinguish two types of variability and transitions in the Chew Bahir aridity record and compare them with the ODP Site 967 wetness index from the eastern Mediterranean. The first type of variability is one of slow variations with cycles of ∼20 kyr, reminiscent of the Earth's precession cycle, and subharmonics of this orbital cycle. In addition to these cyclical wet-dry fluctuations in the area, extreme events often occur, i.e. short wet or dry episodes, lasting for several centuries or even millennia, and rapid transitions between these wet and dry episodes. The second type of variability is characterized by relatively low variation on orbital time scales, but significant century-millennium-scale variations with progressively increasing frequencies. Within this type of variability there are extremely fast transitions between dry and wet within a few decades or years, in contrast to those within Type 1 with transitions over several hundreds of years. Type 1 variability probably reflects the influence of precessional forcing in the lower latitudes at times with maximum values of the long (400 kyr) eccentricity cycle of the Earth's orbit around the sun, with the tendency towards extreme events. Type 2 variability seems to be linked with minimum values of this cycle. There does not seem to be a systematic correlation between Type 1 or Type 2 variability with atmospheric CO2 concentration. The different types of variability and the transitions between those types had important effects on the availability of water, and could have transformed eastern Africa's environment considerably, which would have had important implications for the shaping of the habitat of H. sapiens and the direct ancestors of this species