Retraction speed and chronic poststernotomy pain: A randomized controlled trial.

OBJECTIVES: Approximately 30% of patients develop chronic poststernotomy pain (CPSP) following cardiac surgery with sternal retraction. Risk factors have been described but no causal determinants identified. Investigators hypothesized that opening the sternum slowly would impart less force (and thereby less nerve/tissue damage) and translate to a reduced incidence of CPSP. The main objectives were to determine whether or not slower sternal retraction would reduce the incidence of CPSP and improve health-related quality of life. METHODS: Patients undergoing coronary artery bypass graft surgery were recruited to this randomized controlled trial. Patients were randomized to slow or standard retraction (ie, sternum opened over 15 minutes vs 30 seconds, respectively). Although the anesthesiologist and surgeon were aware of the randomization, the patients, assessors, and postoperative nursing staff remained blinded. Sternotomy pain and analgesics were measured in hospital. At 3, 6, and 12 months postoperatively, all patients completed the Medical Outcomes Survey Short Form and reported on CPSP and complications requiring rehospitalization. Thirty-day rehospitalizations and mortality were recorded. RESULTS: In total, 326 patients consented to participate and 313 were randomized to slow (n = 159) versus standard retraction (n = 154). No clinically relevant differences were detected in acute pain, analgesic consumption, or the incidence of CPSP or health-related quality of life. Although the slow group had significantly more hospitalizations at 3 and 12 months postoperatively, the reasons were unrelated to retraction speed. No differences were observed in 30-day rehospitalizations or mortality. CONCLUSIONS: All outcomes were consistent with previous reports, but no clinically significant differences were observed with retraction speed.

Direct observations of melting, freezing, and ocean circulation in an ice shelf basal crevasse.

Ocean conditions near the grounding zones of Antarctica's ice shelves play a key role in controlling the outflow and mass balance of the ice sheet. However, ocean observations in these regions are largely absent. Here, we present a detailed spatial survey collected with an underwater vehicle in a basal crevasse located in the ocean cavity at the Ross Ice Shelf grounding zone. The observations depict fine-scale variability in ocean forcing that drives asymmetric melting along the lower crevasse sidewalls and freezing in the upper reaches of the crevasse. Freshwater release from melting at depth and salt rejection from freezing above drives an overturning circulation. This vertical circulation pattern overlays a dominant throughflow jet, which funnels water parallel to the coastline, orthogonal to the direction of tidal currents. Importantly, these data reveal that basal crevasses influence ocean circulation and mixing at ice shelf grounding zones to an extent previously unknown.

Use of accounting concepts to study research: return on investment in XSEDE, a US cyberinfrastructure service.

This paper uses accounting concepts-particularly the concept of Return on Investment (ROI)-to reveal the quantitative value of scientific research pertaining to a major US cyberinfrastructure project (XSEDE-the eXtreme Science and Engineering Discovery Environment). XSEDE provides operational and support services for advanced information technology systems, cloud systems, and supercomputers supporting non-classified US research, with an average budget for XSEDE of US$20M+ per year over the period studied (2014-2021). To assess the financial effectiveness of these services, we calculated a proxy for ROI, and converted quantitative measures of XSEDE service delivery into financial values using costs for service from the US marketplace. We calculated two estimates of ROI: a Conservative Estimate, functioning as a lower bound and using publicly available data for a lower valuation of XSEDE services; and a Best Available Estimate, functioning as a more accurate estimate, but using some unpublished valuation data. Using the largest dataset assembled for analysis of ROI for a cyberinfrastructure project, we found a Conservative Estimate of ROI of 1.87, and a Best Available Estimate of ROI of 3.24. Through accounting methods, we show that XSEDE services offer excellent value to the US government, that the services offered uniquely by XSEDE (that is, not otherwise available for purchase) were the most valuable to the facilitation of US research activities, and that accounting-based concepts hold great value for understanding the mechanisms of scientific research generally.

Increased air temperature decreases high-speed, but not total distance, in international field hockey.

This study investigated the effect of heat stress on locomotor activity within international field hockey at team, positional and playing-quarter levels. Analysis was conducted on 71 matches played by the Malaysia national men's team against 24 opponents. Fixtures were assigned to match conditions, based on air temperature [COOL (14 ± 3°C), WARM (24 ± 1°C), HOT (27 ± 1°C), or VHOT (32 ± 2°C), p < 0.001]. Relationships between locomotor metrics and air temperature (AIR), absolute and relative humidity, and wet bulb globe temperature (WBGT) were investigated further using correlation and regression analyses. Increased AIR and WBGT revealed similar correlations (p < 0.01) with intensity metrics; high-speed running (AIR r = -0.51, WBGT r = -0.45), average speed (AIR r = -0.48, WBGT r = -0.46), decelerations (AIR r = -0.41, WBGT r = -0.41), sprinting efforts (AIR r = -0.40, WBGT r = -0.36), and sprinting distance (AIR r = -0.37, WBGT r = -0.29). In comparison to COOL, HOT, and VHOT matches demonstrated reduced high-speed running intensity (-14-17%; p < 0.001), average speed (-5-6%; p < 0.001), sprinting efforts (-17%; p = 0.010) and decelerations per min (-12%; p = 0.008). Interactions were found between match conditions and playing quarter for average speed (+4-7%; p = 0.002) and sprinting distance (+16-36%; p < 0.001), both of which were higher in the fourth quarter in COOL versus WARM, HOT and VHOT. There was an interaction for "low-speed" (p < 0.001), but not for "high-speed" running (p = 0.076) demonstrating the modulating effect of air temperature (particularly >25°C) on pacing within international hockey. These are the first data demonstrating the effect of air temperature on locomotor activity within international men's hockey, notably that increased air temperature impairs high-intensity activities by 5-15%. Higher air temperatures compromise high-speed running distances between matches in hockey.

Rapid basal melting of the Greenland Ice Sheet from surface meltwater drainage.

Subglacial hydrologic systems regulate ice sheet flow, causing acceleration or deceleration, depending on hydraulic efficiency and the rate at which surface meltwater is delivered to the bed. Because these systems are rarely observed, ice sheet basal drainage represents a poorly integrated and uncertain component of models used to predict sea level changes. Here, we report radar-derived basal melt rates and unexpectedly warm subglacial conditions beneath a large Greenlandic outlet glacier. The basal melt rates averaged 14 mm ⋅d-1 over 4 months, peaking at 57 mm ⋅d-1 when basal water temperature reached +0.88 ∘C in a nearby borehole. We attribute both observations to the conversion of potential energy of surface water to heat in the basal drainage system, which peaked during a period of rainfall and intense surface melting. Our findings reveal limitations in the theory of channel formation, and we show that viscous dissipation far surpasses other basal heat sources, even in a distributed, high-pressure system.

Clinical effects of hypertonic saline boluses in children with severe traumatic brain injury.

AIM: To quantify the effects of 3% hypertonic saline (HTS) boluses on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in children. METHODS: A retrospective study of patients admitted to a regional neurosurgical children's intensive care unit. RESULTS: A total of 156 HTS boluses were given to children with traumatic brain injury. ICP decreased 6 mmHg (P < 0.01) and CPP increased 4 mmHg (P = 0.003) 1-h post-bolus. Effects persisted for 3 h post-dose ICP was 5 mmHg lower) and 4 h post-bolus CPP was 3 mmHg higher. ICP change was not associated with pre-bolus serum sodium concentration. CONCLUSIONS: Hypertonic saline 3% at 5 mL/kg is an effective osmolar therapy for reducing ICP and increasing CPP in children for up to 3 h. '53-53' is a suitable guide - 5 mL/kg of 3% HTS will on average decrease ICP by at least 5 mmHg for 3 h. Pre-bolus serum sodium concentration is not correlated with effect size.

Evaluation of carbonic anhydrase IX as a potential therapeutic target in urothelial carcinoma.

OBJECTIVE: Carbonic anhydrase IX (CA9) is important in the regulation of intra- and extracellular pH in solid tumors, contributing to cell growth and invasion. In urothelial carcinoma (UC), CA9 has been identified as a urinary marker for disease detection, but its biologic role is unknown. To date, differential gene expression patterns of CA9 in various molecular subtypes and potential effects of CA9 inhibition in UC cells are unknown. We aimed to investigate the function of CA9 and the effects of CA9 inhibition in invasive UC. METHODS: Immunohistochemistry was used to assess CA9 expression in a cohort of 153 patients undergoing radical cystectomy. CA9 expression was correlated with molecular subtype by analysis of the TCGA data and of our own cohort of 223 patients with invasive UC receiving neoadjuvant chemotherapy. CA9 expression was assessed in a panel of 12 UC cell lines by Western Blot and qPCR, and multiple siRNAs were used to silence CA9 in 2 cell lines. Effects of CA9 silencing on cell growth, migration, and invasion were assessed. We also used the small molecule inhibitor U-104 to inhibit CA9 in vitro and in an orthotopic xenograft model. RESULTS: CA9 expression was higher in cancer tissue compared to benign urothelium and was particularly highly expressed in luminal papillary and basal squamous tumors. CA9 expression did not correlate with outcome after neoadjuvant chemotherapy and/or radical cystectomy. Silencing of CA9 by siRNA diminished invasion but did not induce a consistent change of cell growth and migration. Treatment with U-104 led to cell growth reduction only at high concentrations in vitro and failed to have a significant effect on tumor growth in vivo. CONCLUSIONS: The present study confirms over-expression of CA9 in UC and for the first time shows a correlation with molecular subtypes. However, CA9 expression showed no association with the outcome of patients with muscle invasive bladder cancer and inhibition of CA9 did not lead to a consistent inhibition of tumor growth. Based on these data, CA9 exhibits a role neither as a predictive or prognostic marker nor as a therapeutic target in invasive UC.

Volume and Intensity of Locomotor Activity in International Men's Field Hockey Matches Over a 2-Year Period.

The locomotor demands of international men's field hockey matches were investigated across positions (DEF, MID, FWD) and playing quarters. Volume (i.e., total values) and intensity (i.e., relative to playing time) data were collected using 10-Hz GPS/100-Hz accelerometer units from the #11 world-ranked (WR) team, during 71 matches, against 24 opponents [WR 12 ± 11 (range, 1-60)]. Mean ± SD team total distance (TD) was 4,861 ± 871 m, with 25% (1,193 ± 329 m) "high-speed running" (>14.5 km h-1) and 8% (402 ± 144 m) "sprinting" (>19.0 km h-1). Reduced TD (range, -3 to 4%) and average speed (range, -3.4 to 4.7%) occurred through subsequent quarters, vs. Q1 (p < 0.05). A "large" negative relationship (r = -0.64) was found between playing duration and average speed. Positional differences (p < 0.05) were identified for all volume metrics including; playing duration (DEF, 45:50 ± 8:00 min; MID, 37:37 ± 7:12 min; FWD, 33:32 ± 6:22 min), TD (DEF, 5,223 ± 851 m; MID, 4,945 ± 827 m; FWD, 4,453 ± 741 m), sprinting distance (DEF, 315 ± 121 m; MID, 437 ± 144 m; FWD, 445 ± 129 m), and acceleration efforts (>2 m s-2; DEF, 48 ± 12; MID, 51 ± 11; FWD, 50 ± 14). Intensity variables similarly revealed positional differences (p < 0.05) but with a different pattern between positions; average speed (DEF, 115 ± 10 m min-1; MID, 132 ± 10 m min-1; FWD, 134 ± 15 m min-1), sprinting (DEF, 7 ± 3 m min-1; MID, 12 ± 4 m min-1; FWD, 14 ± 4 m min-1), and accelerations (DEF, 1.1 ± 0.3 n min-1; MID, 1.4 ± 0.2 n min-1; FWD, 1.5 ± 0.3 n min-1). Physical outputs reduced across playing quarters, despite unlimited substitutions, demonstrating the importance of optimizing physical preparation prior to international competition. Volume and intensity data highlight specific positional requirements, with forwards displaying shorter playing durations but greater high-intensity activities than defenders.

The effect of lower airway inflammation on inflammatory cytokine gene expression in bronchoalveolar lavage fluid and whole blood in racing Thoroughbreds.

BACKGROUND: Immunological mechanisms involved in the pathogenesis of mild to moderate equine asthma (MEA) are not completely understood. There are limited data on bronchoalveolar lavage fluid (BALF) and blood inflammatory cytokine profiles in racehorses with MEA, and the effect of racing on inflammatory cytokines is unknown. HYPOTHESIS/OBJECTIVES: We hypothesized that inflammatory cytokine gene expression in BALF and resting blood would be higher in racehorses with lower airway inflammation compared to healthy controls, and that gene expression in blood collected immediately post-race would be increased compared to resting blood in racehorses with lower airway inflammation. ANIMALS: 38 racing Thoroughbreds (samples: 30 resting blood, 22 post-race BALF, 41 post-race blood). METHODS: Prospective observational study. Inflammatory cytokine gene expression was determined in resting blood, post-race BALF and post-race blood from racehorses with lower airway inflammation and controls. RESULTS: Lower airway inflammation was diagnosed in 79 % of racehorses (23 % neutrophilic, 67 % mastocytic, and 10 % mixed). There was no difference in gene expression in BALF or resting blood between racehorses with lower airway inflammation and controls. IL-8 gene expression was higher in post-race blood compared to resting peripheral blood, regardless of disease (p = 0052). BALF neutrophil proportions increased with increasing IL-1ß gene expression in all sample types (p = 0.0025). BALF mast cell proportions increased with increasing TNF-α gene expression in post-race blood (p = 0.015). CONCLUSIONS AND CLINICAL IMPORTANCE: Lower airway inflammation was common in a population of racehorses without respiratory signs or exercise intolerance. Exercise alone increased peripheral blood IL-8 gene expression. Inflammatory cytokine gene expression was not increased in BALF or resting blood in horses with subclinical lower airway inflammation, precluding its diagnostic utility in clinical practice.

Ocean mixing and heat transport processes observed under the Ross Ice Shelf control its basal melting.

The stability of large Antarctic ice shelves has important implications for global sea level, sea ice area, and ocean circulation. A significant proportion of ice mass loss from these ice shelves is through ocean-driven melting which is controlled by largely unobserved oceanic thermodynamic and circulatory processes in the cavity beneath the ice shelf. Here we use direct measurements to provide evidence of the changing water column structure in the cavity beneath the Ross Ice Shelf, the planet's largest ice shelf by area. The cavity water column data exhibit both basal and benthic boundary layers, along with evidence of tidally modulated and diffusively convecting internal mixing processes. A region of thermohaline interleaving in the upper-middle water column indicates elevated diffusion and the potential to modify the cavity circulation. The measurements were recorded using the Aotearoa New Zealand Ross Ice Shelf Program hot water drill borehole melted in the central region of the shelf in December 2017 (HWD2), only the second borehole through the central region of the ice shelf, following J9 in 1977. These data, and comparison with the 1977 data, provide valuable insight into ice shelf cavity circulation and aid understanding of the evolution of the presently stable Ross Ice Shelf.

Seizure Detection Algorithms in Critically Ill Children: A Comparative Evaluation.

OBJECTIVES: To evaluate the performance of commercially available seizure detection algorithms in critically ill children. DESIGN: Diagnostic accuracy comparison between commercially available seizure detection algorithms referenced to electroencephalography experts using quantitative electroencephalography trends. SETTING: Multispecialty quaternary children's hospital in Canada. SUBJECTS: Critically ill children undergoing electroencephalography monitoring. INTERVENTIONS: Continuous raw electroencephalography recordings (n = 19) were analyzed by a neurophysiologist to identify seizures. Those recordings were then converted to quantitative electroencephalography displays (amplitude-integrated electroencephalography and color density spectral array) and evaluated by six independent electroencephalography experts to determine the sensitivity and specificity of the amplitude-integrated electroencephalography and color density spectral array displays for seizure identification in comparison to expert interpretation of raw electroencephalography data. Those evaluations were then compared with four commercial seizure detection algorithms: ICTA-S (Stellate Harmonie Version 7; Natus Medical, San Carlos, CA), NB (Stellate Harmonie Version 7; Natus Medical), Persyst 11 (Persyst Development, Prescott, AZ), and Persyst 13 (Persyst Development) to determine sensitivity and specificity in comparison to amplitude-integrated electroencephalography and color density spectral array. MEASUREMENTS AND MAIN RESULTS: Of the 379 seizures identified on raw electroencephalography, ICTA-S detected 36.9%, NB detected 92.3%, Persyst 11 detected 75.9%, and Persyst 13 detected 74.4%, whereas electroencephalography experts identified 76.5% of seizures using color density spectral array and 73.7% using amplitude-integrated electroencephalography. Daily false-positive rates averaged across all recordings were 4.7 with ICTA-S, 126.3 with NB, 5.1 with Persyst 11, 15.5 with Persyst 13, 1.7 with color density spectral array, and 1.5 with amplitude-integrated electroencephalography. Both Persyst 11 and Persyst 13 had sensitivity comparable to that of electroencephalography experts using amplitude-integrated electroencephalography and color density spectral array. Although Persyst 13 displayed the highest sensitivity for seizure count and seizure burden detected, Persyst 11 exhibited the best trade-off between sensitivity and false-positive rate among all seizure detection algorithms. CONCLUSIONS: Some commercially available seizure detection algorithms demonstrate performance for seizure detection that is comparable to that of electroencephalography experts using quantitative electroencephalography displays. These algorithms may have utility as early warning systems that prompt review of quantitative electroencephalography or raw electroencephalography tracings, potentially leading to more timely seizure identification in critically ill patients.

Seizure Identification by Critical Care Providers Using Quantitative Electroencephalography.

OBJECTIVES: To compare the performance of critical care providers with that of electroencephalography experts in identifying seizures using quantitative electroencephalography display tools. DESIGN: Diagnostic accuracy comparison among healthcare provider groups. SETTING: Multispecialty quaternary children's hospital in Canada. SUBJECTS: ICU fellows, ICU nurses, neurophysiologists, and electroencephalography technologists. INTERVENTION: Two-hour standardized one-on-one training, followed by a supervised individual review of 27 continuous electroencephalography recordings with the task of identifying individual seizures on eight-channel amplitude-integrated electroencephalography and color density spectral array displays. MEASUREMENTS AND MAIN RESULTS: Each participant reviewed 27 continuous electroencephalograms comprising 487 hours of recording containing a total of 553 seizures. Performance for seizure identification was compared among groups using a nested model analysis with adjustment for interparticipant variability within groups and collinearity among recordings. Using amplitude-integrated electroencephalography, sensitivity for seizure identification was comparable among ICU fellows (83.8%), ICU nurses (73.1%), and neurophysiologists (81.5%) but lower among electroencephalographic technologists (66.7%) (p = 0.003). Using color density spectral array, sensitivity was comparable among ICU fellows (82.4%), ICU nurses (88.2%), neurophysiologists (83.3%), and electroencephalographic technologists (73.3%) (p = 0.09). Daily false-positive rates were also comparable among ICU fellows (2.8 for amplitude-integrated electroencephalography, 7.7 for color density spectral array), ICU nurses (4.2, 7.1), neurophysiologists (1.2, 1.5), and electroencephalographic technologists (0, 0) (p = 0.41 for amplitude-integrated electroencephalography; p = 0.13 for color density spectral array). However, performance varied greatly across individual electroencephalogram recordings. Professional background generally played a greater role in determining performance than individual skill or electroencephalogram recording characteristics. CONCLUSIONS: Following standardized training, critical care providers and electroencephalography experts displayed similar performance for identifying individual seizures using both amplitude-integrated electroencephalography and color density spectral array displays. Although these quantitative electroencephalographic trends show promise as a tool for bedside seizure screening by critical care providers, these findings require confirmation in a real-world ICU environment and in daily clinical use.

Selective Inhibition of the Lactate Transporter MCT4 Reduces Growth of Invasive Bladder Cancer.

The significance of lactate transporters has been recognized in various cancer types, but their role in urothelial carcinoma remains mostly unknown. The aim of this study was to investigate the functional importance of the monocarboxylate transporter (MCT) 4 in preclinical models of urothelial carcinoma and to assess its relevance in patient tumors. The association of MCT4 expression with molecular subtypes and outcome was determined in The Cancer Genome Atlas (TCGA) cohort and two independent cohorts of patients with urothelial carcinoma. Silencing of MCT4 was performed using siRNAs in urothelial carcinoma cell lines. Effects of MCT4 inhibition on cell growth, apoptosis, and production of reactive oxygen species (ROS) were assessed. Moreover, effects on lactate efflux were determined. The in vivo effects of MCT4 silencing were assessed in an orthotopic xenograft model. MCT4 expression was higher in the basal subtype. Decreased MCT4 methylation and increased RNA and protein expression were associated with worse overall survival (OS). Inhibition of MCT4 led to a reduction in cell growth, induction of apoptosis, and an increased synthesis of ROS. MCT4 inhibition resulted in intracellular accumulation of lactate. In vivo, stable knockdown of MCT4 reduced tumor growth. The expression of MCT4 in urothelial carcinoma is associated with features of aggressive tumor biology and portends a poor prognosis. Inhibition of MCT4 results in decreased tumor growth in vitro and in vivo Targeting lactate metabolism via MCT4 therefore provides a promising therapeutic approach for invasive urothelial carcinoma, especially in the basal subtype.

PTPα is required for laminin-2-induced Fyn-Akt signaling to drive oligodendrocyte differentiation.

Extrinsic signals that regulate oligodendrocyte maturation and subsequent myelination are essential for central nervous system development and regeneration. Deficiency in the extracellular factor laminin-2 (Lm2, comprising the α2ß1γ1 chains), as occurs in congenital muscular dystrophy, can lead to impaired oligodendroglial development and aberrant myelination, but many aspects of Lm2-regulated oligodendroglial signaling and differentiation remain undefined. We show that receptor-like protein tyrosine phosphatase α (PTPα, also known as PTPRA) is essential for myelin basic protein expression and cell spreading during Lm2-induced oligodendrocyte differentiation. PTPα complexes with the Lm2 receptors α6ß1 integrin and dystroglycan to transduce Fyn activation upon Lm2 engagement. In this way, PTPα mediates a subset of Lm2-induced signals required for differentiation, includeing mTOR-dependent Akt activation but not Erk1/2 activation. We identify N-myc downstream regulated gene-1 (NDRG1) as a PTPα-regulated molecule during oligodendrocyte differentiation, and distinguish Lm2 receptor-specific modes of Fyn-Akt-dependent and -independent NDRG1 phosphorylation. Altogether, this reveals an Lm2-regulated PTPα-Fyn-Akt signaling axis that is critical for key aspects of the gene expression and morphological changes that mark oligodendrocyte maturation.

AR-V7 Transcripts in Whole Blood RNA of Patients with Metastatic Castration Resistant Prostate Cancer Correlate with Response to Abiraterone Acetate.

PURPOSE: The expression of AR-V7 (androgen receptor splice variant) 7 in circulating tumor cells has been associated with resistance to abiraterone and enzalutamide in patients with metastatic castration resistant prostate cancer. We used a sensitive, whole blood reverse transcriptase-polymerase chain reaction assay that does not require circulating tumor cell enrichment to correlate outcomes of abiraterone with whole blood expression of AR-V7 and other prostate cancer associated transcripts. MATERIALS AND METHODS: We assessed the expression of AR-V7, FOXA1, GRHL2, HOXB13, KLK2, KLK3 and TMPRSS2:ERG mRNA in 2.5 ml whole blood from each of 27 patients with metastatic castration resistant prostate cancer and 33 controls without cancer as the discovery cohort. Cycle threshold values of controls with the highest gene expression were set as the threshold for a positive test. Thresholds were then applied to a validation cohort of 37 patients with metastatic castration resistant prostate cancer who were commencing abiraterone. Gene expression was correlated with the prostate specific antigen response rate using the chi-square test, and with time to prostate specific antigen progression and overall survival using the log rank test. RESULTS: In the discovery cohort 3 of 27 patients (11.1%) with metastatic castration resistant prostate cancer were AR-V7 positive vs 4 of 37 (10.8%) in the validation cohort. In the validation cohort patients with a positive AR-V7 test had a lower prostate specific antigen response rate (0% vs 42%, p = 0.27) together with shorter median prostate specific antigen progression (0.7 vs 4.0 months, p <0.001) and median overall survival (5.5 vs 22.1 months, p <0.001). CONCLUSIONS: Reverse transcriptase-polymerase chain reaction detection of AR-V7 transcripts in whole blood was associated with inferior outcomes in patients treated with abiraterone. These results reinforce the potential usefulness of AR-V7 as a prognostic and predictive biomarker for metastatic castration resistant prostate cancer.

Assessing the sensitivity of diffusion MRI to detect neuronal activity directly.

Functional MRI (fMRI) is widely used to study brain function in the neurosciences. Unfortunately, conventional fMRI only indirectly assesses neuronal activity via hemodynamic coupling. Diffusion fMRI was proposed as a more direct and accurate fMRI method to detect neuronal activity, yet confirmative findings have proven difficult to obtain. Given that the underlying relation between tissue water diffusion changes and neuronal activity remains unclear, the rationale for using diffusion MRI to monitor neuronal activity has yet to be clearly established. Here, we studied the correlation between water diffusion and neuronal activity in vitro by simultaneous calcium fluorescence imaging and diffusion MR acquisition. We used organotypic cortical cultures from rat brains as a biological model system, in which spontaneous neuronal activity robustly emerges free of hemodynamic and other artifacts. Simultaneous fluorescent calcium images of neuronal activity are then directly correlated with diffusion MR signals now free of confounds typically encountered in vivo. Although a simultaneous increase of diffusion-weighted MR signals was observed together with the prolonged depolarization of neurons induced by pharmacological manipulations (in which cell swelling was demonstrated to play an important role), no evidence was found that diffusion MR signals directly correlate with normal spontaneous neuronal activity. These results suggest that, whereas current diffusion MR methods could monitor pathological conditions such as hyperexcitability, e.g., those seen in epilepsy, they do not appear to be sensitive or specific enough to detect or follow normal neuronal activity.

Debating LGBT Workplace Protections in the Bible Belt: Social Identities in Legislative and Media Discourse.

This article reports a case study of the legislative and media discourse surrounding the addition of sexual orientation and gender identity language to the employment nondiscrimination ordinance of a city in the heart of the Bible Belt. The purpose of the study is to uncover how different identities were constructed and contested at city council meetings and in the news media on the way to passing legal protection for LGBT city employees in a region that is often characterized by anti-gay prejudice. This debate over the nondiscrimination ordinance centered on the question of whether LGBT identities are equivalent to identity categories based on race, gender, or religious belief, and it was shaped by various intergroup communication dynamics, specifically between members of the LGBT minority and the straight majority, between LGBT and Christian identities, and between "true" and "false" Christian identities.

Simultaneous calcium fluorescence imaging and MR of ex vivo organotypic cortical cultures: a new test bed for functional MRI.

Recently, several new functional (f)MRI contrast mechanisms including diffusion, phase imaging, proton density, etc. have been proposed to measure neuronal activity more directly and accurately than blood-oxygen-level dependent (BOLD) fMRI. However, these approaches have proved difficult to reproduce, mainly because of the dearth of reliable and robust test systems to vet and validate them. Here we describe the development and testing of such a test bed for non-BOLD fMRI. Organotypic cortical cultures were used as a stable and reproducible biological model of neuronal activity that shows spontaneous activity similar to that of in vivo brain cortex without any hemodynamic confounds. An open-access, single-sided magnetic resonance (MR) "profiler" consisting of four permanent magnets with magnetic field of 0.32 T was used in this study to perform MR acquisition. A fluorescence microscope with long working distance objective was mounted on the top of a custom-designed chamber that keeps the organotypic culture vital, and the MR system was mounted on the bottom of the chamber to achieve real-time simultaneous calcium fluorescence optical imaging and MR acquisition on the same specimen. In this study, the reliability and performance of the proposed test bed were demonstrated by a conventional CPMG MR sequence acquired simultaneously with calcium imaging, which is a well-characterized measurement of neuronal activity. This experimental design will make it possible to correlate directly the other candidate functional MR signals to the optical indicia of neuronal activity in the future.

Enantioselective palladium(0)-catalyzed Nazarov-type cyclization.

A Pd(0)-catalyzed asymmetric Nazarov-type cyclization is described. The optimized ligand for the reaction incorporates a weakly coordinating pyridine ring into a TADDOL-derived phosphoramidite (TADDOL=α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol). The reaction leads to the formation of cyclopentenones as single diastereoisomers that incorporate two contiguous asymmetric centers, one tertiary and one an all-carbon-atom quaternary stereocenter, in high yield and optical purity. It is noteworthy that the reaction does not require that substrates should be activated by aryl substituents.

Organometallic chemistry of ethynyl boronic acid MIDA ester, HC≡CB(O2CCH2)2NMe.

The reactions of HC≡CBMIDA (BMIDA = B(O2CCH2)2NMe) with a range of ruthenium complexes afford the first isolated examples of σ-alkynyl, σ-alkenyl and vinylidene complexes bearing 4-coordinate boron substituents. Specifically, the reactions of HC≡CBMIDA with [RuH(S2CNR2)(CO)(PPh3)2] (R = Me, Et) and [Ru(CO)2(PPh3)3] afford the alkynyl complexes [Ru(C≡CBMIDA)(S2CNR2)(CO)(PPh3)2] and [RuH(C≡CBMIDA)(CO)2(PPh3)2], the latter being converted to [Ru(C≡CBMIDA)Cl(CO)2(PPh3)2] on treatment with chloroform. With [RuCl(dppe)2]PF6 the vinylidene salt [RuCl(=C=CHBMIDA)(dppe)2]PF6 is obtained, which reacts with Et3N to afford the neutral alkynyl derivative [Ru(C≡CBMIDA)Cl(dppe)2]. Hydrometallation of HC≡CBMIDA by [RuHCl(CO)(PPh3)3] affords the coordinatively unsaturated σ-alkenyl complex [RuCl(CH=CHBMIDA)(CO)(PPh3)2] which in turn reacts with CO, CNC6H2Me3-2,4,6, [Et2NH2][S2CNEt2] or K[HB(pz)3] (pz = pyrazol-1-yl) to afford the coordinatively saturated complexes [Ru(CH=CHBMIDA)Cl(CO)2(PPh3)2], [Ru(CH=CHBMIDA)Cl(CO)(CNC6H2Me3)(PPh3)2], [Ru(CH=CHBMIDA)(S2CNEt2)(CO)-(PPh3)2] and [Ru(CH=CHBMIDA)(CO)(PPh3){HB(pz)3}]. In all cases, the transannular N→B dative bond is retained in the BMIDA substituent.