Goblet cell hyperplasia is a feature of the adaptive response to jejunoileal bypass in rats

The role of goblet cells in the adaptive response of the intestine to jejunoileal bypass was studied in rats submitted to an 85% end-to-side jejunoileal bypass or sham bypass. At 36 weeks the length and wet weight of the duodenum and large bowel was 13-48% greater in animals with jejunoileal bypass. Measurements of villous height and crypt depth confirmed mucosal hyperplasia in the residual functioning small bowel and the distal colon. Histochemical studies in both groups of rats showed an overall predominance of sulphomucins throughout the intestinal tract, but jejunoileal bypass caused a disproportionate increase in the number of sialomucin containing goblet cells in functioning segments of small bowel and distal colon. An abundance of sialomucin cells at the site of anastomosis after jejunoileal bypass may have been a protective response to local mechanical trauma. Goblet cell hyperplasia is a feature of compensatory growth of the intestinal tract after surgical shortening. The changes in colonic mucin seen after jejunoileal bypass resemble those observed in ulcerative colitis and mucosal dysplasia.     

Irrational exuberance and neural crash warning signals during endogenous experimental market bubbles

Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during pathological overvaluations—price bubbles. The connection between the behavioral and neural underpinnings of such phenomena has been absent, in part due to a lack of enabling technology. We used a multisubject functional MRI paradigm to measure neural activity in human subjects participating in experimental asset markets in which endogenous price bubbles formed and crashed. Although many ideas exist about how and why such bubbles may form and how to identify them, our experiment provided a window on the connection between neural responses and behavioral acts (buying and selling) that created the bubbles. We show that aggregate neural activity in the nucleus accumbens (NAcc) tracks the price bubble and that NAcc activity aggregated within a market predicts future price changes and crashes. Furthermore, the lowest-earning subjects express a stronger tendency to buy as a function of measured NAcc activity. Conversely, we report a signal in the anterior insular cortex in the highest earners that precedes the impending price peak, is associated with a higher propensity to sell in high earners, and that may represent a neural early warning signal in these subjects. Such markets could be a model system to understand neural and behavior mechanisms in other settings where emergent group-level activity exhibits mistaken belief or valuation.Asset price bubbles are extended periods in which prices rise well above fundamental values. Identifying bubbles and predicting crashes from price data alone is a notoriously difficult problem (1). However, prices are created by the collective behavior of the market participants, so neural activity could offer biomarkers for the evolution of price bubbles. Studies of asset price bubbles indicate a role for psychological factors such as “euphoria” (2), “irrational exuberance” (3), “mania” (4), “animal spirits” (5), and “sentiment” (6). We sought neural data supporting such psychological constructs that might help to identify price bubbles.We observed the formation and crash of endogenous bubbles in experimental asset markets (7, 8) using multisubject neuroimaging. In each of 16 market sessions, consisting of an average of 20 traders (range, 11–23), we measured the neural activity of 2–3 participants (n = 44 total) using functional magnetic resonance imaging (fMRI). Our market design is based upon ref. 9. Traders could buy or sell one risky asset unit in each period. Fig. 1A illustrates the sequence of experimental events. Each market had 50 trading periods. All subjects began with 100 units of experimental currency (a risk-free asset) and 6 units of a risky asset. Each period, the risky asset paid a currency dividend d of either 0.40 or 1.00 per unit (with equal probability), creating an expected dividend E[d] = 0.70. Currency earned a fixed interest rate r of 5% each period. After all 50 rounds of trading were completed, the risky asset was redeemed for 14 units of the risk-free currency.Open in a separate windowFig. 1.Asset market experiment. (A) Each period subjects viewed the following screens, in order: Positions, Order Entry (×5), Trading Results, and Dividends and Interest. (B) Order elicitation procedure. Subjects responded Buy, Sell, or Hold to a random (uniform) price draw from each of five bins, each of width equal to 10% of the last period’s price. The middle bin was centered on the last period’s price. (C) How the price is chosen (=market clearing). The highest price at which subjects responded Buy, and the lowest price at which subjects responded Sell, were entered into a closed book call market. Prices and trading outcomes were reported on the Trading Results screen.These parameters defined an unambiguous fundamental value for the risky asset. Buying the risky asset in period t at price P_t and selling it one period later leads to the expected net gain E_t[P_t+1] ? P_t? + ?E[d]. The same investment of P_t in the risk-free asset yields a sure net gain of rP_t. If these two amounts are equal—in economic terms, if asset prices are “in equilibrium”—then there is a stationary price equal to a constant fundamental value F defined by F = E[d]/r = 0.70/0.05 = 14. Prices persistently above F = 14 indicate a bubble; such a clear bubble measure is rarely available in field data. Fig. 2A illustrates the price paths for all 16 markets in this experiment. Bubbles are typical and large: the median price peak was 64.30 (range, 19.68–156.01). The bubble paths always result in a crash, and prices in the final period are near the fundamental F = 14 (median, 14.13). Fig. 2B illustrates a typical experimental session. This market bubble crashed after period 30. Trading volume is substantial, which means that prices do not result from a few extreme traders.Open in a separate windowFig. 2.Endogenous market bubbles. (A) Price paths in16 different experimental market sessions. The dark line shows the average price in each period over the 16 sessions. Plotted below the prices is the normalized per-subject volume for each period; error bars are SEs. (B) Single-session prices (Top) and trading volume (Middle) from one statistically typical experimental session. At Bottom is shown the risky asset holdings; each subject is indicated by a different color. MRI subjects are shown with thicker lines. The dashed line is the “clairvoyant” profit-maximizing share path (assuming subjects could somehow correctly anticipate all future prices).     

Cancer patient-reported outcomes assessment using wireless touch screen tablet computers

Purpose

To assess the feasibility of collecting patient-reported outcomes data with wireless touch screen tablet computers in the adult oncology palliative care setting.

Methods

Patients were provided with tablet computers during scheduled clinic visits and answered online queries about their experience over the past week in the health domains of anxiety, depression, fatigue, pain interference, physical function, instrumental social support, sleep impairment, diarrhea, constipation, nausea, vomiting, anorexia, dyspnea, neuropathy, and spiritual values.

Results

Content analysis of patient interviews indicates that wireless touch screen tablet computers are a feasible approach for collecting patient-reported outcome measures by palliative care cancer patients presenting in clinic. Most patients indicated that the questionnaire was easy to answer. However, all but one patient requested some form of assistance, and many reported difficulties attributable to a lack of familiarity with the device, interpretation of certain questions, and wireless connectivity-related issues.

Conclusions

This feasibility study demonstrates that tablet computers have the potential to efficiently and reliably collect patient-reported health status measures among palliative care cancer patients presenting in clinics. The use of these devices may lead to substantial improvements by making patient-reported outcomes available for clinical decision-making.     

Development of Oxacillin Resistance in a Patient with Recurrent Staphylococcus aureus Bacteremia

Whole-genome sequencing was used to compare longitudinal isolates of Staphylococcus aureus that developed resistance to oxacillin (MIC up to 16 μg/ml). The mecA gene was absent. A novel 5-bp TATCC frameshift insertion in a gene encoding an ABC transporter similar to that of the teichoic acid translocation ATP-binding protein TagH and a 3-bp GCT nonframeshift insertion in the pdhA pyruvate dehydrogenase gene were detected in the oxacillin-resistant isolates.     

Frontal EEG delta/alpha ratio and screening for post-stroke cognitive deficits: The power of four electrodes

This study analysed correlations between post-stroke, quantitative electroencephalographic (QEEG) indices, and cognition-specific, functional outcome measures. Results were compared between QEEG indices calculated from the standard 19 versus 4 frontal (or 4 posterior) electrodes to assess the feasibility and efficacy of employing a reduced electrode montage. Resting-state EEG was recorded at the bedside within 62–101 h after onset of symptoms of middle cerebral artery, ischaemic stroke (confirmed radiologically). Relative power for delta, theta, alpha and beta, delta/alpha ratio (DAR) and pairwise-derived brain symmetry index (pdBSI) were averaged; over all electrodes (global), over F3, F4, F7, F8 (frontal) and P3, P4, T5, T6 (posterior). The functional independence measure and functional assessment measure (FIM–FAM) was administered at mean 105 days post-stroke. Total (30 items) and cognition-specific (5 items) FIM–FAM scores were correlated with QEEG indices using Spearman's coefficient, with a Bonferroni correction. Twenty-five patients were recruited, 4 died within 3 months and 1 was lost to follow-up. Hence 20 cases (10 female; 9 left hemisphere; mean age 68 years, range 38–84) were analysed. Two QEEG indices demonstrated highly-significant correlations with cognitive outcomes: frontal DAR (ρ = − 0.664, p ≤ 0.001) and global, relative alpha power (ρ = 0.67, p ≤ 0.001). After correction there were no other significant correlations. Alpha activity – particularly frontally – may index post-stroke attentional capacity, which appears to be a key determinant of functional and cognitive outcomes. Likewise frontal delta pathophysiology influences such outcomes. Pending further studies, DAR from 4 frontal electrodes may inform early screening for post-MCA stroke cognitive deficits, and thereby, clinical decisions.     

Anterior Segment Anatomy and Conventional Outflow Physiology of the Tree Shrew (Tupaia belangeri)

PurposeRodent and primate models are commonly used in glaucoma research; however, both have their limitations. The tree shrew (Tupaia belangeri) is an emerging animal model for glaucoma research owing in part to having a human-like optic nerve head anatomy, specifically a collagenous load-bearing lamina. However, the anterior segment anatomy and function have not been extensively studied in the tree shrew. Thus, the purpose of this study was to provide the first detailed examination of the anterior segment anatomy and aqueous outflow facility in the tree shrew.MethodsAqueous outflow dynamics were measured in five ostensibly normal eyes from three tree shrews using the iPerfusion system over a range of pressures. Gross histological assessment and immunohistochemistry were performed to characterize anterior segment anatomy and to localize several key molecules related to aqueous outflow.ResultsAnterior segment anatomy in tree shrews is similar to humans, demonstrating a scleral spur, a multilayered trabecular meshwork and a circular Schlemm''s canal with a single lumen. Average outflow facility was 0.193 µL/min/mm Hg (95% confidence interval, 0.153–0.244), and was stable over time. Outflow facility was more similar between contralateral eyes (approximately 5% average difference) than between eyes of different animals. No significant dependence of outflow facility on time or pressure was detected (pressure–flow nonlinearity parameter of 0.01 (95% % confidence interval, −0.29 to 0.31 CI µL/min/mm Hg).ConclusionsThese studies lend support to the usefulness of the tree shrew as a novel animal model in anterior segment glaucoma and pharmacology research. The tree shrew''s cost, load-bearing collagenous lamina cribrosa, and lack of washout or anterior chamber deepening provides a distinct experimental and anatomic advantage over the current rodent and nonhuman primate models used for translational research.