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Intracerebral hemorrhage (ICH), which comprises 15 percent to 30 percent of all strokes, has an estimated incidence of 37,000 cases per year. One third of patients are actively bleeding when they present to the emergency department, and hematoma growth during the first hours after ICH onset is thought to be a prime determinant of clinical deterioration. Inflammation, as opposed to ischemia, also negatively affects patient condition. Recombinant activated factor VII is emerging as a potential first-line therapy, especially in warfarin-associated hemorrhage. Corticosteroid therapy is not supported by contemporary studies or by current management guidelines. Aggressive blood pressure reduction is under investigation. Surgical intervention has shown no statistically significant benefit over medical management for patients with ICH in general, although subgroup analysis in a large randomized trial suggested potential benefits from surgery for patients with lobar ICH. Not long ago, ICH was considered virtually untreatable. Diligent efforts in both bench and clinical research are generating hope for patients who experience this catastrophic event. [ABSTRACT FROM AUTHOR]

The comparative incremental validity of five self-as-context measures in predicting psychological distress and satisfaction with life, after controlling for relevant demographic variables and other psychological flexibility processes, was evaluated in a college student sample ( N = 315). All of the measures except the self-as-context subscale of the Multidimensional Psychological Flexibility Inventory (Rolffs et al., 2018) separately accounted for a significant increase in variability in psychological distress. The centering subscale of the Self-as-Context Scale (Zettle et al., 2018) was the only measure to also display incremental predictive validity in accounting for significant variance in life satisfaction. The conceptual and clinical implications of the findings in the context of study limitations are discussed., (© 2024 Springer Publishing Company.)

C-H bond activation enables the facile synthesis of new chemicals. While C-H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C-H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C-C coupling mediated by 2D TMDCs to promote C-H activation and carbon dots synthesis. Our results shed light on 2D materials for C-H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials., (© 2024. The Author(s).)

Lithium fluoride (LiF) is a ubiquitous component in the solid electrolyte interphase (SEI) layer in Li-ion batteries. However, its nanoscale structure, morphology, and topology, important factors for understanding LiF and SEI film functionality, including electrode passivity, are often unknown due to limitations in spatial resolution of common characterization techniques. Ultrabroadband near-field synchrotron infrared nanospectroscopy (SINS) enables such detection and mapping of LiF in SEI layers in the far-infrared region down to ca. 322 cm -1 with a nanoscale spatial resolution of ca. 20 nm. The surface sensitivity of SINS and the large infrared absorption cross section of LiF, which can support local surface phonons under certain circumstances, enabled characterization of model LiF samples of varying structure, thickness, surface roughness, and degree of crystallinity, as confirmed by atomic force microscopy, attenuated total reflectance FTIR, SINS, X-ray photoelectron spectroscopy, high-angle annular dark-field, and scanning transmission electron microscopy. Enabled by this approach, LiF within SEI films formed on Cu, Si, and metallic glass Si 40 Al 50 Fe 10 electrodes was detected and characterized. The nanoscale morphologies and topologies of LiF in these SEI layers were evaluated to gain insights into LiF nucleation, growth, and the resulting nuances in the electrode surface passivity.

Brain metastases (BMs) are an emerging challenge in oncology due to increasing incidence and limited treatments. Here, we present results of a single-arm, open-label, phase 2 trial evaluating intracranial efficacy of pembrolizumab, a programmed cell death protein 1 inhibitor, in 9 patients with untreated BMs (cohort A) and 48 patients with recurrent and progressive BMs (cohort B) across different histologies. The primary endpoint was the proportion of patients achieving intracranial benefit, defined by complete response, partial response or stable disease. The primary endpoint was met with an intracranial benefit rate of 42.1% (90% confidence interval (CI): 31-54%). The median overall survival, a secondary endpoint, was 8.0 months (90% CI: 5.5-8.7 months) across both cohorts, 6.5 months (90% CI: 4.5-18.7 months) for cohort A and 8.1 months (90% CI: 5.3-9.6 months) for cohort B. Seven patients (12.3%), encompassing breast, melanoma and sarcoma histologies, had overall survival greater than 2 years. Thirty patients (52%; 90% CI: 41-64%) had one or more grade-3 or higher adverse events that were at least possibly treatment related. Two patients had grade-4 adverse events (cerebral edema) that were deemed at least possibly treatment related. These results suggest that programmed cell death protein 1 blockade may benefit a select group of patients with BMs, and support further studies to identify biomarkers and mechanisms of resistance. ClinicalTrials.gov identifier: NCT02886585., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To examine providers' perceptions of integrated care prior to the merger of a university's student health center and counseling services. Participants: Seventeen providers across student health services (n = 9) and counseling (n = 8) agreed to participate in the qualitative study . Method: Semi-structured individual interviews that focused on the perceived benefits and challenges of the merger were conducted in December 2019. Following the interviews, a thematic analysis was completed. Results: The perceived benefits noted by providers centered on the ability of an interdisciplinary team to improve the coordination of, access to, and quality of care delivered to students. However, more anticipated challenges were reported by providers (e.g., differences in training and care protocols, losing one's autonomy as a provider). Conclusions: This qualitative study provides a more in-depth analysis of providers' perceptions of integrated care prior to implementation in a university setting and may have implications for model adoption.

The solid electrolyte interphase (SEI) on a Si negative electrode in carbonate-based organic electrolytes shows intrinsically poor passivating behavior, giving rise to unsatisfactory calendar life of Li-ion batteries. Moreover, mechanical strains induced in the SEI due to large volume changes of Si during charge-discharge cycling could contribute to its mechanical instability and poor passivating behavior. This study elucidates the influence that static mechanical deformation of the SEI has on the rate of unwanted parasitic reactions at the Si/electrolyte interface as a function of electrode potential. The experimental approach involves the utilization of Si thin-film electrodes on substrates with disparate elastic moduli, which either permit or suppress the SEI deformation in response to Si volume changes upon charging-discharging. We find that static mechanical stretching and deformation of the SEI results in an increased parasitic electrolyte reduction current on Si. Furthermore, attenuated total reflection and near-field Fourier-transform infrared nanospectroscopy reveal that the static mechanical stretching and deformation of the SEI fosters a selective transport of linear carbonate solvent through, and nanoconfinement within, the SEI. These, in turn, promote selective solvent reduction and continuous electrolyte decomposition on Si electrodes, reducing the calendar life of Si anode-based Li-ion batteries. Finally, possible correlations between the structure and chemical composition of the SEI layer and its mechanical and chemical resilience under prolonged mechanical deformation are discussed in detail.

Si anodes for Li-ion batteries are notorious for their large volume expansion during lithiation and the corresponding detrimental effects on cycle life. However, calendar life is the primary roadblock for widespread adoption. During calendar life aging, the main origin of impedance increase and capacity fade is attributed to the instability of the solid electrolyte interphase (SEI). In this work, we use ex situ nano-Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy to characterize the structure and composition of the SEI layer on amorphous Si thin films after an accelerated calendar aging protocol. The characterization of the SEI on non-washed and washed electrodes shows that brief washing in dimethyl carbonate results in large changes to the film chemistry and topography. Detailed examination of the non-washed electrodes during the first lithiation and after an accelerated calendar aging protocol reveals that PF 6 - and its decomposition products tend to accumulate in the SEI due to the preferential transport of PF 6 - ions through polyethylene oxide-like species in the organic part of the SEI layer. This work demonstrates the importance of evaluating the SEI layer in its intrinsic, undisturbed form and new strategies to improve the passivation of the SEI layer are proposed.

Background: Shift work has been associated with adverse pregnancy outcomes. The objective of this study was to evaluate the association between sleep disturbances and adverse pregnancy outcomes., Methods and Findings: This was a secondary analysis of a prospective study of participants enrolled in a prospective observational study wherein gravidae were screened for sleep apnea (2010-2012). A screening questionnaire with standard sleep apnea questionnaires as well as novel items about shift work and nocturnal sleep duration was administered at a prenatal care visit. Short sleep duration was defined as less than 7 hours. Prolonged sleep duration was defined as greater than 9 hours. In a cohort of 1125 pregnant people, 9.4% reported shift work at the time of screening. Gravidae who reported shift work were more likely than gravidae who reported no shift work to develop preeclampsia (28.3% versus 13.0%, P<0.001), preeclamspsia with severe features (16.0% versus 8.5%, P = 0.010), gestational diabetes (28.3% versus 19.9%, P = 0.041), and a composite of adverse obstetric outcomes (61.3% versus 47.8%, P = 0.008). After adjusting for potentially confounding variables, shift work was associated with an increased risk for preeclampsia with (adjusted relative risk (aRR) 1.70, 95% CI 1.03-2.79, p = 0.036) and without (aRR 2.03, 95% CI 1.43-2.90, p<0.001) severe features, and gestational diabetes mellitus class A1 (aRR 1.47, 95% CI 1.05-2.05, p = 0.023) and class A2 (aRR 1.67, 95% CI 1.13-2.44, p = 0.009). Sleep duration was associated with gestational diabetes (31.3% among those with short sleep duration, 25.2% among those with normal sleep duration and 14.0% among those with prolonged sleep duration, P<0.001) and gestational diabetes class A2 (29.5%, 17.9%, and 10.1%, respectively, P<0.001). Gravidae with prolonged sleep duration experienced less composite adverse pregnancy outcomes at 42.6% compared to 57.4% for those with short sleep duration or 52.5% for those with normal sleep duration, P = 0.002., Conclusions: Shift work and sleep duration are both associated with adverse pregnancy outcomes. Further research on the impact of sleep disturbance on pregnancy outcomes is warranted., Competing Interests: The authors have declared that no competing interests exist.

Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently an end stage of the disease. Immune checkpoint inhibitors (ICI) provide a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique elements of the MBM TME and correlates of MBM response to ICI, we collected 32 fresh MBM and performed single-cell RNA sequencing of the MBM TME and T-cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity in the MBM TME, most notably multiple distinct neutrophil states, including an IL8-expressing population that correlated with malignant cell epithelial-to-mesenchymal transition. In addition, we observed significant relationships between intracranial T-cell phenotypes and the distribution of T-cell clonotypes intracranially and peripherally. We found that the phenotype, clonotype, and overall number of MBM-infiltrating T cells were associated with response to ICI, suggesting that ICI-responsive MBMs interact with peripheral blood in a manner similar to extracranial lesions. These data identify unique features of the MBM TME that may represent potential targets to improve clinical outcomes for patients with MBM., (©2022 American Association for Cancer Research.)

Solid-state batteries possess the potential to significantly impact energy storage industries by enabling diverse benefits, such as increased safety and energy density. However, challenges persist with physicochemical properties and processes at electrode/electrolyte interfaces. Thus, there is great need to characterize such interfaces in situ, and unveil scientific understanding that catalyzes engineering solutions. To address this, we conduct multiscale in situ microscopies (optical, atomic force, and infrared near-field) and Fourier transform infrared spectroscopies (near-field nanospectroscopy and attenuated total reflection) of intact and electrochemically operational graphene/solid polymer electrolyte interfaces. We find nanoscale structural and chemical heterogeneities intrinsic to the solid polymer electrolyte initiate a cascade of additional interfacial nanoscale heterogeneities during Li plating and stripping; including Li-ion conductivity, electrolyte decomposition, and interphase formation. Moreover, our methodology to nondestructively characterize buried interfaces and interphases in their native environment with nanoscale resolution is readily adaptable to a number of other electrochemical systems and battery chemistries., (© 2022. The Author(s).)

We investigated the effects of regular walking in green and suburban environments on heart rate variability (HRV) and blood pressure (BP) in middle-aged adults. Twenty-three adults participated in a non-randomized crossover experiment comprised of once-weekly 50-min moderate-intensity walking sessions. Separated by a two-week washout period, participants walked for three weeks in each of two treatment conditions (green and suburban) in a local arboretum and suburban sidewalks of Chaska, MN. Eleven participants completed green walking first and 12 suburban walking first. Walks were split into 15-min intra-walk phases, with phases representing each walk's beginning, middle, and final 15-min. Repeated measures linear mixed models evaluated (1) HRV phase differences between treatments and HRV change within treatments, and (2) pre- and post-walk BP differences between treatments and pre-to post-walk BP changes. Intra-walk phase analyses revealed higher HRV during green walking vs. suburban walking during phase 2 (p < 0.0001) and phase 3 (p = 0.02). Less HRV reduction was seen between intra-walk phases 1 and 2 during green vs. suburban walking (p = 0.02). Pre-to post-walk changes revealed decreased mean systolic BP for both green (p = 0.0002) and suburban (p = 0.003) walking conditions, but not for diastolic BP. Post-walk BP results were similar after both green walking and suburban walking. In summary, walking sessions in a green environment elicited greater beneficial HRV responses compared to a suburban environment. Additionally, walking in either environment, green or suburban, promoted reductions in systolic BP., Competing Interests: Declaration of competing interest Authors have no conflicts of interest to report., (Copyright © 2020 Elsevier Inc. All rights reserved.)

President Trump and his administration have been regarded by news outlets and scholars as one of the most hostile administrations towards scientists and their work. However, no study to-date has empirically measured how federal scientists perceive the Trump administration with respect to their scientific work. In 2018, we distributed a survey to over 63,000 federal scientists from 16 federal agencies to assess their perception of scientific integrity. Here we discuss the results of this survey for a subset of these agencies: Department of Interior (DOI) agencies (the US Fish and Wildlife Service (FWS), the US Geological Survey, and the National Park Service); the Centers for Disease Control and Prevention (CDC); the US Environmental Protection Agency (EPA); the Food and Drug Administration (FDA); and the National Oceanic and Atmospheric Administration (NOAA). We focus our analysis to 10 key questions fitting within three core categories that relate to perceptions of integrity in science. Additionally, we analyzed responses across agencies and compare responses in the 2018 survey to prior year surveys of federal scientists with similar survey questions. Our results indicate that federal scientists perceive losses of scientific integrity under the Trump Administration. Perceived loss of integrity in science was greater at the DOI and EPA where federal scientists ranked incompetent and untrustworthy leadership as top barriers to science-based decision-making, but this was not the case at the CDC, FDA, and NOAA where scientists positively associated leadership with scientific integrity. We also find that reports of political interference in scientific work and adverse work environments were higher at EPA and FWS in 2018 than in prior years. We did not find similar results at the CDC and FDA. These results suggest that leadership, positive work environments, and clear and comprehensive scientific integrity policies and infrastructure within agencies play important roles in how federal scientists perceive their agency's scientific integrity., Competing Interests: The authors have declared that no competing interests exist.

Background: Virtual Reality (VR) has been increasingly employed as a therapeutic means to help patients reduce stress, anxiety, and pain. While it has been shown to be effective in multiple settings, there is still scant literature referencing its use in the pediatric intensive care unit (ICU) and none using VR longitudinally as a vehicle for mindful focus utilizing natural environments., Objectives: This proof of concept study aims to demonstrate that the use of 3-D Nature-Based Therapy (NBT) glasses will lead to a reduction in pain, nausea, and anxiety in children and adolescents undergoing Total Pancreatectomy Islet Auto-Transplant (TPIAT)., Methods: Six pediatric patients (8-18 yr.) scheduled to receive TPIAT were recruited over a one-year period. Patients rated their symptoms using various scoring methods, including a novel nature-based anxiety scale. If VR was used prior to a physical therapy session, this was also noted. Patients then utilized the Oculus ™ VR device and re-scored their symptoms. Interviews were performed at entry to study, post-ICU, and at hospital discharge., Results: Four of six recruited patients utilized the VR device, three of whom completed pre- and post-use scores during 11 encounters, though many other encounters occurred without scoring. Of the two patients not utilizing the device, one chose to use other means of distraction and the other reported nausea and chose not to use device. Of the patients who utilized the device, there was a net decrease in symptom scores after use, including the use of the nature-based scale which mimicked both validated scales. On survey results, all patients who utilized the device found it to be "enjoyable" and "helpful", either "would" or "might use" it again, and "would recommend it to others" for use., Conclusions: In this proof of concept study, children in a critical care setting were able to utilize VR devices for NBT after extensive surgical procedures. Initial quantitative scoring systems suggest overall improvement in symptom management, and reactions by both patients and their parents were overall positive., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We present a new methodology that enables studies of the molecular structure of graphene-liquid interfaces with nanoscale spatial resolution. It is based on Fourier transform infrared nanospectroscopy (nano-FTIR), where the infrared (IR) field is plasmonically enhanced near the tip apex of an atomic force microscope (AFM). The graphene seals a liquid electrolyte reservoir while acting also as a working electrode. The photon transparency of graphene enables IR spectroscopy studies of its interface with liquids, including water, propylene carbonate, and aqueous ammonium sulfate electrolyte solutions. We illustrate the method by comparing IR spectra obtained by nano-FTIR and attenuated total reflection (which has a detection depth of a few microns) demonstrating that the nano-FTIR method makes it possible to determine changes in speciation and ion concentration in the electric double and diffuse layers as a function of bias.

This study investigated the acute effects of repeated walking sessions within green and suburban environments on participants' psychological (anxiety and mood) and cognitive (directed-attention) outcomes. Twenty-three middle-aged adults (19 female) participated in a non-randomized crossover study comprised of once-weekly 50-min moderate-intensity walking sessions. Participants walked for three weeks in each of two treatment conditions: green and suburban, separated by a two-week washout period. Eleven participants completed green walking first and 12 suburban walking first. For each walk, we used validated psychological questionnaires to measure pre- and post-walk scores for: (1) mood, evaluated via the Positive and Negative Affect Schedule (PANAS); (2) anxiety, assessed by the State-Trait Anxiety Inventory (STAI-S); and (3) directed-attention, measured using the visual Backwards Digit Span test (BDS). Repeated measures linear mixed models assessed pre- to post-walk changes within-treatment conditions and post-walk contrasts between-treatment conditions. Results indicated that anxiety decreased after green walking and increased after suburban walking (-1.8 vs. +1.1 units, respectively; p = 0.001). For mood, positive affect improved after green walking and decreased after suburban walking (+2.3 vs. -0.3 units, respectively; p = 0.004), and negative affect decreased after green walking and remained similar after suburban walking (-0.5 vs. 0 units, respectively; p = 0.06). Directed-attention did not improve from pre- to post-walk for either condition. Our results suggested that green walking may be more effective at reducing state anxiety and increasing positive affect compared to suburban walking.

We hypothesized that cows grazing stockpiled tall fescue (STF) during late gestation would have increased nutrient intake, resulting in improved metabolic status and fetal growth compared with cows consuming summer-baled tall fescue hay. Multiparous, spring-calving, crossbred beef cows (year 1: n = 48, year 2: n = 56) were allocated by body weight (BW), body condition score (BCS), age, service sire, and expected calving date to 1 of 2 forage systems (4 rep/system) in mid-November on day 188 of gestation: strip-graze endophyte-infected STF in 4.05 ha pastures or consume ad libitum endophyte-infected summer-baled tall fescue-based hay in uncovered dry lots. Treatments were terminated 1 wk postpartum, and cow-calf pairs were managed together until weaning. Data were analyzed with forage system, year, and their interaction as fixed effects. Sampling day was a repeated effect for cow metabolites and hormones. Calf date of birth was in the model when P < 0.25; pasture or pen was the experimental unit. Cow prepartum BW was not affected (P ≥ 0.424) by forage system, but cows grazing STF tended (P = 0.09) to have greater BCS at day 35 and had greater (P = 0.03) final precalving BCS than hay-fed cows. Additionally, final precalving 12th rib fat thickness tended (P = 0.09) to be greater for STF than hay-fed cows. Calves born to cows fed hay only weighed 10.2% less (P = 0.03) at birth than calves born to cows consuming STF, indicating reduced fetal growth. Postpartum cow BW, BCS, first service conception rate, and overall pregnancy rate were not affected (P ≥ 0.15) by late gestational forage system. After day 0, serum urea N was greater (P < 0.001) in cows consuming STF on all days measured. Cows grazing STF also tended (P = 0.08) to have greater plasma glucose than cows consuming hay. Serum nonesterified fatty acids (NEFA) were greater (P < 0.001) in cows grazing STF on day 56 in year 1 and on day 77 and 99 in year 2. Serum triiodothyronine was less (P = 0.03) on day 0, but greater (P = 0.004) on day 99, in cows grazing STF. Cows grazing STF tended (P = 0.06) to have greater thyroxine on day 77 in year 1. Serum cortisol was greater (P = 0.003) on day 35 and tended (P = 0.10) to be greater on day 99 in cows grazing STF. Calf birth weight was positively correlated with prepartum maternal serum urea N (r = 0.31, P = 0.002) and NEFA (r = 0.12, P = 0.005). In this study, cows grazing STF had increased nutrient intake during late gestation, resulting in greater fetal growth.

Energy storage science calls for techniques to elucidate ion transport over a range of conditions and scales. We introduce a new technique, pascalammetry, in which stress is applied to a solid-state electrochemical device and induced faradaic current transients are measured and analyzed. Stress-step pascalammetry measurements are performed on operando microbattery probes (Li 2 O/Li/W) and Si cathodes, revealing stress-assisted Li + diffusion. We show how non-Cottrellian lithium diffusional kinetics indicates stress, a prelude to battery degradation. An analytical solution to a diffusion/activation equation describes this stress signature, with spatiotemporal characteristics distinct from Cottrell's classic solution for unstressed systems. These findings create an unprecedented opportunity for quantitative detection of stress in solid-state batteries through the current signature. Generally, pascalammetry offers a powerful new approach to study stress-related phenomena in any solid-state electrochemical system.

Weak ties are thought to facilitate the diffusion of information through social networks because of their tendency to span otherwise distant subgroups. However, this logic assumes that weak relationships have the same capacity to transmit information as those that are strong. I argue that weak ties, especially the kind that span subgroups, are often also lower-capacity. Due to a lack of trust, an unwillingness to share benefits, or a limited ability to understand one another, an individual is less likely to share novel information across these ties. In standard models of diffusion imported from epidemiology, even reduced-capacity links would still aid diffusion. However, accounting for reduced capacity in a new model of diffusion that captures realistic features of information sharing in human groups, I demonstrate that hesitation to share across weak links substantially impedes overall diffusion. Moreover, I show that the addition of weak ties to a social network can strictly reduce the extent and speed of information diffusion. Increasing density by adding weak ties can make diffusion strictly worse by crowding out the use of higher-capacity ties. I present the results of simulated information diffusion on both hypothetical networks generated to possess varying levels of density and homophily, as well as on real social networks in two Ugandan villages shown to be responsible for face-to-face information sharing.

Groups of individuals have social networks that structure interactions within the groups; evolutionary theory increasingly uses this fact to explain the emergence of cooperation (Eshel and Cavalli-Sforza, 1982; Boyd and Richerson, 1988, 1989; Ohtsuki et al., 2006; Nowak et al., 2010; Van Veelen et al., 2012). This approach has resulted in a number of important insights for the evolution of cooperation in the biological and social sciences, but omits a key function of social networks that has persisted throughout recent evolutionary history (Apicella et al., 2012): their role in transmitting gossip about behavior within a group. Accounting for this well-established role of social networks among rational agents in a setting of indirect reciprocity not only shows a new mechanism by which the structure of networks is fitness-relevant, but also reveals that knowledge of social networks can be fitness-relevant as well. When groups enforce cooperation by sanctioning peers whom gossip reveals to have deviated, individuals in certain peripheral network positions are tempting targets of uncooperative behavior because gossip they share about misbehavior spreads slowly through the network. The ability to identify these individuals creates incentives to behave uncooperatively. Consequently, groups comprised of individuals who knew precise information about their social networks would be at a fitness disadvantage relative to groups of individuals with a coarser knowledge of their networks. Empirical work has consistently shown that modern humans know little about the structure of their own social networks and perform poorly when tasked with learning new ones. This robust empirical regularity may be the product of natural selection in an environment of strong selective pressure at the group level. Imprecise views of networks make enforcing cooperation easier., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A carbon-nanotube-enabling scanning probe technique/nanotechnology for manipulating and measuring lithium at the nano/mesoscale is introduced. Scanning Li-nanopipette and probe microscopy (SLi-NPM) is based on a conductive atomic force microscope (AFM) cantilever with an open-ended multi-walled carbon nanotube (MWCNT) affixed to its apex. SLi-NPM operation is demonstrated with a model system consisting of a Li thin film on a Si(111) substrate. By control of bias, separation distance, and contact time, attograms of Li can be controllably pipetted to or from the MWCNT tip. Patterned surface Li features are then directly probed via noncontact AFM measurements with the MWCNT tip. The subsequent decay of Li features is simulated with a mesoscale continuum model, developed here. The Li surface diffusion coefficient for a four (two) Li layer thick film is measured as D=8(±1.2)×10(-15) cm(2) s(-1) (D=1.75(±0.15)×10(-15) cm(2) s(-1)). Dual-Li pipetting/measuring with SLi-NPM enables a broad range of time-dependent Li and nanoelectrode characterization studies of fundamental importance to energy-storage research., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To compare the precision of progesterone measurements obtained with the use of immunoassays and of liquid chromatography-tandem mass spectrometry (LC-MS/MS)., Design: Comparative study., Setting: Academic, private practice, and in vitro fertilization (IVF) research centers., Patient(s): A total of 189 human serum samples were collected during controlled ovarian hyperstimulation and early pregnancy in women undergoing IVF., Intervention(s): Serum progesterone pools (n = 10; 0.2-4 ng/mL) were sent to four laboratory centers that used four different automated immunoassay analyzers. Progesterone was measured by immunoassay in triplicate at three separate time points (n = 9 per pool) and by LC-MS/MS in triplicate once (n = 3 per pool)., Main Outcome Measure(s): Inter- and intraassay coefficients of variation (CVs) of progesterone measurements were compared for each analyzer and LC-MS/MS., Result(s): Progesterone measurements by immunoassay were highly correlated with those by LC-MS/MS. Only two analyzers had intraassay CVs <10% at all three experimental time points, and only two analyzers had an interassay CV <10%. Mean progesterone levels by the analyzers were different across multiple progesterone pools., Conclusion(s): Our results indicate that progesterone threshold measurements used for IVF clinical decisions should be interpreted cautiously and based on laboratory- and method-specific data. A validated progesterone standard incorporated into daily immunoassays could improve medical decision accuracy., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

There is increasing interest in using live cell imaging to monitor not just individual intracellular endpoints, but to investigate the interplay between multiple molecular events as they unfold in real time within the cell. A major impediment to simultaneous acquisition of fluorescent signals from multiple probes is that emission spectra of many fluorophores overlap, often with maxima that are only a few nanometers apart. Spectral acquisition of mixed fluorescence signals captured within a dedicated scanning range can be used to quantitatively separate signals into component spectra. We report here the development of a novel live cell application of spectral unmixing for the simultaneous monitoring of intracellular events reported by closely-emitting fluorophores responding dynamically to external stimuli. We validate the performance of dynamic spectral unmixing microscopy (DynSUM) using genetically encoded sensors to simultaneously monitor changes in glutathione redox potential (Egsh) and H2O2 production in living cells exposed to oxidizing and reducing agents. We further demonstrate the utility of the DynSUM approach to observe the relationship between the increases in Egsh and H2O2 generation induced in airway epithelial cells exposed to an environmental electrophile., (Published by Elsevier Inc.)

Emotional stimuli generally command more brain processing resources than non-emotional stimuli, but the magnitude of this effect is subject to voluntary control. Cognitive reappraisal represents one type of emotion regulation that can be voluntarily employed to modulate responses to emotional stimuli. Here, the late positive potential (LPP), a specific event-related brain potential (ERP) component, was measured in response to neutral, positive and negative images while participants performed an evaluative categorization task. One experimental group adopted a "negative frame" in which images were categorized as negative or not. The other adopted a "positive frame" in which the exact same images were categorized as positive or not. Behavioral performance confirmed compliance with random group assignment, and peak LPP amplitude to negative images was affected by group membership: brain responses to negative images were significantly reduced in the "positive frame" group. This suggests that adopting a more positive appraisal frame can modulate brain activity elicited by negative stimuli in the environment.

Background/aims: Current therapy for gastroparesis with prokinetic agents is limited by options and side effects. One macrolide, erythromycin (ERY), is associated with possible sudden cardiac death from QT prolongation due to P450 iso-enzyme inhibition. An alternative, azithromycin (AZI), lacks P450 inhibition. We compared the effect on gastric emptying half-times (t½) between AZI and ERY in patients diagnosed with gastroparesis by gastric emptying scintigraphy., Methods: Patients stopped medications known to affect gastric emptying prior to the study, and then ingested 1 scrambled egg meal labeled with 18.5-37 MBq of technetium-99m sulfur colloid followed by continuous imaging for 120 minutes, at 1 minute per frame. A simple linear fit was applied to the rate of gastric emptying, and gastric emptying t½ was calculated (normal = 45-90 minutes). At 75-80 minutes, if the stomach had clearly not emptied, patients were given either ERY (n = 60) or AZI (n = 60) 250 mg IV and a new post-treatment gastric emptying t½ was calculated., Results: Comparison of gastric emptying t½ showed a similar positive effect (mean gastric emptying t½ for AZI = 10.4 ± 7.2 minutes; mean gastric emptying t½ for ERY = 11.9 ± 8.4 minutes; p = 0.30)., Conclusions: AZI is equivalent to ERY in accelerating the gastric emptying of adult patients with gastroparesis. Given the longer duration of action, better side effect profile and lack of P450 interaction for AZI as compared with ERY, further research should evaluate the long term effectiveness and safety of AZI as a gastroparesis treatment.

22q11.2 Deletion syndrome (22q11.2 DS) [DiGeorge syndrome type 1 (DGS1)] occurs in ∼1:3,000 live births; 75% of children with DGS1 have severe congenital heart disease requiring early intervention. The gold standard for detection of DGS1 is fluorescence in situ hybridization (FISH) with a probe at the TUPLE1 gene. However, FISH is costly and is typically ordered in conjunction with a karyotype analysis that takes several days. Therefore, FISH is underutilized and the diagnosis of 22q11.2 DS is frequently delayed, often resulting in profound clinical consequences. Our goal was to determine whether multiplexed, quantitative real-time PCR (MQPCR) could be used to detect the haploinsufficiency characteristic of 22q11.2 DS. A retrospective blinded study was performed on 382 subjects who had undergone congenital heart surgery. MQPCR was performed with a probe localized to the TBX1 gene on human chromosome 22, a gene typically deleted in 22q11.2 DS. Cycle threshold (C(t)) was used to calculate the relative gene copy number (rGCN). Confirmation analysis was performed with the Affymetrix 6.0 Genome-Wide SNP Array. With MQPCR, 361 subjects were identified as nondeleted with an rGCN near 1.0 and 21 subjects were identified as deleted with an rGCN near 0.5, indicative of a hemizygous deletion. The sensitivity (21/21) and specificity (361/361) of MQPCR to detect 22q11.2 deletions was 100% at an rGCN value drawn at 0.7. One of 21 subjects with a prior clinical (not genetically confirmed) DGS1 diagnosis was found not to carry the deletion, while another subject, not previously identified as DGS1, was detected as deleted and subsequently confirmed via microarray. The MQPCR assay is a rapid, inexpensive, sensitive, and specific assay that can be used to screen for 22q11.2 deletion syndrome. The assay is readily adaptable to high throughput.

Recent evidence has suggested a role for vitamin D in breast cancer prevention and survival. Studies have reported an inverse relation between vitamin D intake and the risk of breast cancer, improvements in survival after a diagnosis of breast cancer in women with higher levels of vitamin D, and vitamin D insufficiency in up to 75% of women with breast cancer. Preclinical data have indicated that vitamin D affects up to 200 genes that influence cellular proliferation, apoptosis, angiogenesis, terminal differentiation of normal and cancer cells, and macrophage function. Vitamin D receptors have been found in up to 80% of breast cancers, and vitamin D receptor polymorphisms have been associated with differences in survival. Although ongoing studies have investigated a possible link between adequate levels of vitamin D and improved cancer prognosis, breast cancer survivors may derive additional, non-cancer-related benefits from adequate vitamin D levels, including improvements in bone mineral density, quality of life, and mood. Maintaining adequate vitamin D stores is recommended for breast cancer survivors throughout their lifetime., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Pet birds can harbor diseases that can be transmitted to their owners. This review describes the presentation, evaluation, and basic treatment of infectious syndromes caused by these bacterial, viral, protozoal, fungal, and parasitic zoonoses.

Breast cancer must be considered in the evaluation of breast masses in men, although various benign causes are more common, including gynecomastia and conditions of the skin and subcutaneous tissue. A patient's history may identify key features suspicious for malignancy or reassuring for benign disease. Physical examination has been documented to be as effective as mammography in distinguishing benign from malignant lesions, and both have been reported as highly accurate for the identification of malignancy. Mammography is therefore best used when the physical examination findings are indeterminate. Ultrasonography may be used as an adjunct to mammography; no evidence supports the use of magnetic resonance imaging in male breast patients. If clinical or mammographic features are suspicious or indeterminate for malignancy, tissue diagnosis is warranted and may be achieved surgically or via core-needle biopsy or fine-needle aspiration cytology. Given the lack of uniformity in the clinical recommendations for the evaluation of breast masses in men, a practical approach is proposed.

Context: Vascular endothelial growth factor A (VEGF-A) is a potent cytokine that promotes angiogenesis and vascular permeability. After controlled ovarian stimulation (COS) for in vitro fertilization (IVF), excessive VEGF-A production can occur, particularly in women with polycystic ovarian syndrome (PCOS); however, it is unclear whether the regulation of VEGF-A production is different between PCOS and non-PCOS women., Objective: The aim of this study was to determine whether there were differences in the dose- and time-dependent effects of insulin and IGFs on VEGF-A production by luteinized granulosa cells (LGCs) from women with and without PCOS., Design and Setting: A prospective comparative experimental study was conducted at an institutional practice., Patients: Patients included six PCOS and six non-PCOS women undergoing COS and IVF., Interventions: Interventions included COS for IVF., Main Outcome Measures: VEGF-A levels in culture media were collected daily for 3 d from LGCs after incubation with variable doses of insulin, IGF-I, and IGF-II in the presence and absence of LH., Results: In both study groups, exposure to LH alone did not alter VEGF-A levels. However, insulin or IGF increased VEGF-A levels within 1 d and appeared to synergize with LH at 3 d. VEGF-A production by non-PCOS LGCs was more sensitive to IGF exposure, whereas PCOS cells were more sensitive to insulin. Although an increase in DNA content (P < 0.05) was noted in cultures of PCOS cells, progesterone levels were lower compared with non-PCOS LGCs., Conclusion: Insulin and IGFs promote VEGF-A production in LGCs, but the response patterns are different when cells from PCOS and non-PCOS women are compared.

It is difficult to perform two tasks at the same time. Such performance limitations are exemplified by the psychological refractory period (PRP): when participants make distinct motor responses to two stimuli presented in rapid succession, the response to the second stimulus is increasingly slowed as the time interval between the two stimuli is decreased. This impairment is thought to reflect a central limitation in selecting the appropriate response to each stimulus, but not in perceptually encoding the stimuli. In the present study, it was sought to determine which brain regions are specifically involved in response selection under dual-task conditions by contrasting fMRI brain activity measured from a response selection manipulation that increased dual-task costs, with brain activity measured from an equally demanding manipulation that affected perceptual visibility. While a number of parieto-frontal areas involved in response selection were activated by both dual-task manipulations, the dorsal pre-motor cortex, and to a lesser extent the inferior frontal cortex, were specifically engaged by the response selection manipulation. These results suggest that the pre-motor cortex is an important neural locus of response selection limitation under dual-task situations.

Spectral imaging is a natural extension of the capabilities of confocal microscopes. The first confocal spectral imaging (CSI) instruments were able to acquire spectral data that allowed the emissions of overlapping fluorescent probes to be assigned to data channels representing a spectrum rather than a range of emission wavelengths. This marked a significant improvement over what could be done by channel series with standard confocal microscopes. However the performance of these earlier designs can fall short in one or more of the following areas; sensitivity, spectral resolution and reproducibility, acquisition speed, and unmixing accuracy. Nikon has recently introduced a new CSI instrument, C1si, that overcomes some of the more serious performance deficiencies of earlier designs through unique optical, electronic, and data handling advances. C1si uses a multianode photomultiplier tube (PMT) as the detector and typically acquires spectral data in a single scan. Sensitivity is enhanced over designs diffracting randomly polarized fluorescence by rotating the polarization of all emission photons to the S-plane, the plane for which the diffraction grating is most efficient. Three diffraction gratings are provided supporting wavelength sampling increments of 2.5, 5, and 10 nm. Improvements have been made in the digitization process to increase detection efficiency as well. C1si is calibrated to a high enough standard that it is possible to share and reproduce data between instruments. The algorithm implemented in the EZ-C1 software is able to accurately and repeatedly unmix fluorescent probes with emission peaks separated by as little as 5 nm. It is possible to unmix probes with emission peaks separated by 20 nm with a 10-1 brightness difference. Three probes can be unmixed with emission peaks contained within a 20 nm range. Acquisition is fast enough and the sensitivity is sufficient for C1si to acquire more than 100 frames of spectral time series data without serious photobleaching., ((c) 2006 International Society for Analytical Cytology.)

When two masked targets (T1 and T2), both requiring attention, are presented within half a second of each other, report of the second target is poor, demonstrating an attentional blink (AB). Potter, Chun, Banks, and Muckenhoupt (1998) argued that all previous demonstrations of an AB occurring when one or more targets were presented outside the visual modality did not represent true AB but were, instead, artifactual, resulting from switching of task set. In the present experiments, T1 and T2 modalities were independent and varied randomly from trial to trial, allowing no useful preparatory task-set switching from T1 to T2. However, reliable ABs were observed when both targets were visual, when both targets were auditory, and cross-modally when T2s were visual. Furthermore, the ABs observed for cross-modality visual T2s showed the characteristic U-shaped pattern often found in AB experiments in which two visual targets are used--a pattern that should not be observed under task-set switching conditions. These results provide evidence that cross-modality AB can be found under conditions that do not allow useful preparatory task-set switching.

Objective: To study and evaluate a sequential, extended embryo culture system., Design: Prospective study., Setting: University-affiliated IVF clinic., Patient(s): All couples who were treated between October 1997 and July 1998., Intervention(s): A standard human tubal fluid plus 10% serum substitute supplement (SSS) culture medium was used. The embryos were transferred to extended culture medium (S2 or G2) on day 3., Main Outcome Measure(s): Blastocyst formation and implantation and pregnancy rates., Result(s): Forty percent of the 20 donated cryopreserved embryos progressed to the blastocyst stage by day 6. Clinically, 7 (5.6%) of the 125 cycles did not result in a transfer. Blastocyst formation rates ranged from 33%-63% in the five study groups. Implantation rates ranged from 15%-52% and pregnancy rates ranged from 37%-75%., Conclusion(s): Extended culture to day 5 or 6 results in acceptable blastocyst formation rates, implantation rates, and pregnancy rates.

Objective: To test a sucrose-glycerol cryoprotectant for IUI-ready sperm preparation., Design: Semen aliquots from normozoospermic donors either were subjected to conventional semen freezing (TES and Tris yolk buffer in 7.4% final glycerol) with post-thaw processing or were preprocessed and frozen in HEPES-buffered human tubal fluid with 1% human serum albumin, 4% sucrose, and 6% glycerol. All aliquots were cooled to 4 degrees C, exposed to liquid nitrogen vapors, and stored in liquid nitrogen. Aliquots from each were processed by centrifugation resuspension or by centrifugation in Percoll (Pharmacia, Alameda, CA) before sperm parameters were analyzed., Setting: University-based andrology laboratory., Main Outcome Measure(s): Recovery of motile sperm., Result(s): Percoll processing produced preparations with higher percentages of motile cells; however, cryopreserved sperm had a lower recovery of motile sperm compared with Percoll-processed fresh semen or centrifugation/resuspension-processed fresh or frozen samples. The percentages of sperm with normal morphologies were significantly increased in the IUI-ready samples compared with samples frozen conventionally. The IUI-ready Percoll-processed sample produced the best results, with a final mean motility of 36% and an overall yield of motile sperm of 17.4%., Conclusion(s): The sucrose-glycerol-based cryoprotectant produced an IUI-ready preparation with motile sperm recovery comparable to that of conventional semen cryopreservation but with improved percent morphology.

Purpose: To determine fetal outcomes and the capability of sonography to help predict these outcomes in patients with maternal serum alpha-fetoprotein (MSAFP) levels of 5.0 multiples of the median or greater., Materials and Methods: Real-time sonography was performed in patients with singleton and multiple gestations. After sonography, the pregnancy was monitored., Results: Inaccurate historical dating caused elevated MSAFP levels in 14 patients. In the remaining 72 singleton gestations, 42 fetuses (58%) had anomalies, 13 (18%) died in utero or after birth, three (4%) had intrauterine growth retardation or were premature, and 14 (19%) were normal, with no complications. A poor outcome occurred in 58 (80%) of the singleton pregnancies, and sonography depicted an abnormality in 49 (84%) of these patients., Conclusion: Most pregnant patients with MSAFP levels of 5.0 MOM or greater have an unfavorable outcome. Sonography depicts most of these abnormal pregnancies.

Marked discrepancies (values up to four times higher in on assay than in the other) were observed when the plasma concentration of immunoreactive human calcitonin (iCT) was measured by two radioimm8noassays in 18 patients with medullary thyroid carcinoma. The two antisera used had different binding affinities for the NH2- and COOH-terminal regions of synthetic calcitonin monomer (CT-1-32). Except for this difference, the assays were identical and reacted equally with CT 1-32. Plasma samples from patients with medullary thyroid carcinoma were gel filtered on columns of Bio-Gel P-150, and the immunoreactivity in column effuent fractions was measured with both assays. The one utilizing the antiserum with prominent NH2-terminal binding affinity (and giving higher iCT values) recognized at least five molecular species that eluted with or before CT 1-32. The other assay, utilizing the antiserum with a COOH-terminal binding affinity, recognized two fo these molecular species-one eluting with CT 1-32 and the other in a position consistent with a dimer. A mixture of athreotic asthma and added CT 1-32 contained a single immunologic species that was recoqnized equally by both antisera. No forms smaller than CT 1-32 were detected in any study. The results suggest that iCT circulating in the plasma of patients with medullary thryoid carcinoma is hetergeneous. The absolute iCT concentration measured by radioimmunoassays depends on recognition of these distinct molecular species as well as on the specific binding affinities of the antiserum used to detect them. These observations may partially explain the variations among iCT values reported by different laboratories.

The histocompatibility antigen HLA-B27 was determined in 43 patients with post-traumatic spinal cord injury (SCI). The prevalence of B27 was significantly increased in the SCI patients with ectopic ossification. Five of 21 patients with ectopic bone had B27 compared to none of the 22 patients without ossification (P = 0.021). This finding indicates that HLA-B27 is a genetically determined risk factor for the development of heterotopic ossification following injury to the central nervous system. Future studies may determine that HLA-typing can identify a group of patients at a high risk of a disabling complication of SCI who should be treated prophylactically to prevent ectopic bone.

From 1968 to 1973, the number of dermatologists in the United States per 100,000 population gradually increased from 1.6 to 1.8, with the West and Northeast regions showing relatively higher rates and the South and North Central regions showing relatively lower rates. The variation in rate, considered by geographic divisions, can be analyzed to identify areas in the United States that may be in need of additional dermatologists. Given the current number of dermatologists being certified by the American Board of Dermatology and given the current death rate, there appear to be a sufficient number of dermatologists to ensure future growth.