Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex

The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up “core” thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of consciousness

A system�based intervention to reduce Black�White disparities in the treatment of early stage lung cancer: A pragmatic trial at five cancer centers

Background: Advances in early diagnosis and curative treatment have reduced high mortality rates associated with non�small cell lung cancer. However, racial disparity in survival persists partly because Black patients receive less curative treatment than White patients. Methods: We performed a 5�year pragmatic, trial at five cancer centers using a system�based intervention. Patients diagnosed with early stage lung cancer, aged 18�85 were eligible. Intervention components included: (1) a real�time warning system derived from electronic health records, (2) race�specific feedback to clinical teams on treatment completion rates, and (3) a nurse navigator. Consented patients were compared to retrospective and concurrent controls. The primary outcome was receipt of curative treatment. Results: There were 2841 early stage lung cancer patients (16% Black) in the retrospective group and 360 (32% Black) in the intervention group. For the retrospective baseline, crude treatment rates were 78% for White patients vs 69% for Black patients (P < 0.001); difference by race was confirmed by a model adjusted for age, treatment site, cancer stage, gender, comorbid illness, and income�odds ratio (OR) 0.66 for Black patients (95% CI 0.51�0.85, P = 0.001). Within the intervention cohort, the crude rate was 96.5% for Black vs 95% for White patients (P = 0.56). Odds ratio for the adjusted analysis was 2.1 (95% CI 0.41�10.4, P = 0.39) for Black vs White patients. Between group analyses confirmed treatment parity for the intervention. Conclusion: A system�based intervention tested in five cancer centers reduced racial gaps and improved care for all

Evaluating Potential Racial Inequities in Low-dose Computed Tomography Screening for Lung Cancer

BACKGROUND: Lung cancer is the leading cause of cancer death in the US, and significant racial disparities exist in lung cancer outcomes. For example, Black men experience higher lung cancer incidence and mortality rates than their White counterparts. New screening recommendations for low-dose computed tomography (LDCT) promote earlier detection of lung cancer in at-risk populations and can potentially help mitigate racial disparities in lung cancer mortality if administered equitably. Yet, little is known about the extent of racial differences in uptake of LDCT. OBJECTIVE: To evaluate potential racial disparities in LDCT screening in a large community-based cancer center in central North Carolina. METHODS: We conducted a retrospective study of the initial patients undergoing LDCT in a community-based cancer center (n = 262). We used the Pearson chi-squared test to assess potential racial disparities in LDCT screening. RESULTS: Study results suggest that Black patients may be less likely than White patients to receive LDCT screening when eligible (χ2 = 51.41, p &lt; 0.0001). CONCLUSION: Collaboration among healthcare providers, researchers, and decision makers is needed to promote LDCT equity

Preempting Racial Inequities in Lung Cancer Screening

Lung cancer is the leading cause of cancer death in the U.S., and Black patients experience higher lung cancer incidence and mortality than White patients.1 Lung cancer screening facilitates diagnoses at earlier, more treatable stages. In 2011, low-dose computed tomography (LDCT) showed a relative reduction in lung cancer-specific mortality by 20% in the National Lung Screening Trial (NLST), a multisite randomized controlled trial comparing LDCT and chest radiography for lung cancer screening (N=53,454).2 NLST results indicated that LDCT reduces lung cancer mortality in all racial groups, but a stronger effect was observed among Black patients.3 Therefore, LDCT has potential to mitigate racial disparities in lung cancer mortality. However, this potential can only be achieved with equitable LDCT utilization

The visible hand: finger ratio (2D:4D) and competitive bidding

In an experiment using two-bidder first-price sealed bid auctions with symmetric independent private values and 400 subjects, we scan also the right hand of each subject. We study how the ratio of the length of the index and ring fingers (2D:4D) of the right hand, a measure of prenatal hormone exposure, is correlated with bidding behavior and total profits. 2D:4D has been reported to predict competitiveness in sports competition (Manning and Taylor, 2001, and Hoenekopp, Manning, and Mueller, 2006), risk aversion in lottery tasks (Dreber and Hoffman, 2007, Garbarino et al., 2010), and the average profitability of high-frequency traders in financial markets (Coates, Gurnell, and Rustichini, 2009). We do not find any significant correlation between 2D:4D on either bidding or profits. However, there might be racial differences in the correlation between 2D:4D and bidding and profits

A novel retinoblastoma therapy from genomic and epigenetic analyses.

Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss

The preparation of large surface area lanthanum based perovskite supports for AuPt nanoparticles: tuning the glycerol oxidation reaction pathway by switching the perovskite B site

Gold and gold alloys, in the form of supported nanoparticles, have been shown over the last three decades to be highly effective oxidation catalysts. Mixed metal oxide perovskites, with their high structural tolerance, are ideal for investigating how changes in the chemical composition of supports affect the catalysts' properties, while retaining similar surface areas, morphologies and metal co-ordinations. However, a significant disadvantage of using perovskites as supports is their high crystallinity and small surface area. We report the use of a supercritical carbon dioxide anti-solvent precipitation methodology to prepare large surface area lanthanum based perovskites, making the deposition of 1 wt% AuPt nanoparticles feasible. These catalysts were used for the selective oxidation of glycerol. By changing the elemental composition of the perovskite B site, we dramatically altered the reaction pathway between a sequential oxidation route to glyceric or tartronic acid and a dehydration reaction pathway to lactic acid. Selectivity profiles were correlated to reported oxygen adsorption capacities of the perovskite supports and also to changes in the AuPt nanoparticle morphologies. Extended time on line analysis using the best oxidation catalyst (AuPt/LaMnO3) produced an exceptionally high tartronic acid yield. LaMnO3 produced from alternative preparation methods was found to have lower activities, but gave comparable selectivity profiles to that produced using the supercritical carbon dioxide anti-solvent precipitation methodology

Antiretroviral Drug Use in a Cross-Sectional Population Survey in Africa

BackgroundAntiretroviral (ARV) drug treatment benefits the treated individual and can prevent HIV transmission. We assessed ARV drug use in a community-randomized trial that evaluated the impact of behavioral interventions on HIV incidence.MethodsSamples were collected in a cross-sectional survey after a 3-year intervention period. ARV drug testing was performed using samples from HIV-infected adults at 4 study sites (Zimbabwe; Tanzania; KwaZulu-Natal and Soweto, South Africa; survey period 2009-2011) using an assay that detects 20 ARV drugs (6 nucleoside/nucleotide reverse transcriptase inhibitors, 3 nonnucleoside reverse transcriptase inhibitors, and 9 protease inhibitors; maraviroc; raltegravir).ResultsARV drugs were detected in 2011 (27.4%) of 7347 samples; 88.1% had 1 nonnucleoside reverse transcriptase inhibitors ± 1-2 nucleoside/nucleotide reverse transcriptase inhibitors. ARV drug detection was associated with sex (women&gt;men), pregnancy, older age (&gt;24 years), and study site (P &lt; 0.0001 for all 4 variables). ARV drugs were also more frequently detected in adults who were widowed (P = 0.006) or unemployed (P = 0.02). ARV drug use was more frequent in intervention versus control communities early in the survey (P = 0.01), with a significant increase in control (P = 0.004) but not in intervention communities during the survey period. In KwaZulu-Natal, a 1% increase in ARV drug use was associated with a 0.14% absolute decrease in HIV incidence (P = 0.018).ConclusionsThis study used an objective, biomedical approach to assess ARV drug use on a population level. This analysis identified factors associated with ARV drug use and provided information on ARV drug use over time. ARV drug use was associated with lower HIV incidence at 1 study site

One class classification as a practical approach for accelerating π–π co-crystal discovery

Machine learning using one class classification on a database of existing co-crystals enables the identification of co-formers which are likely to form stable co-crystals, resulting in the synthesis of two co-crystals of polyaromatic hydrocarbons.</p

Sustained methane emissions from China after 2012 despite declining coal production and rice-cultivated area

China’s anthropogenic methane emissions are the largest of any country in the world. A recent study using atmospheric observations suggested that recent policies aimed at reducing emissions of methane due to coal production in China after 2010 had been largely ineffective. Here, based on a longer observational record and an updated modelling approach, we find a statistically significant positive linear trend (0.36 ± 0.04 ( $\pm1\sigma$ ) Tg CH _4 yr ^−2 ) in China’s methane emissions for 2010–2017. This trend was slowing down at a statistically significant rate of -0.1 ± 0.04 Tg CH _4 yr ^−3 . We find that this decrease in growth rate can in part be attributed to a decline in China’s coal production. However, coal mine methane emissions have not declined as rapidly as production, implying that there may be substantial fugitive emissions from abandoned coal mines that have previously been overlooked. We also find that emissions over rice-growing and aquaculture-farming regions show a positive trend (0.13 ± 0.05 Tg CH _4 yr ^−2 for 2010–2017) despite reports of shrinking rice paddy areas, implying potentially significant emissions from new aquaculture activities, which are thought to be primarily located on converted rice paddies