Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels1 are essential for pacemaking activity and neural signalling2,3. Drugs inhibiting HCN1 are promising candidates for management of neuropathic pain4 and epileptic seizures5. The general anaesthetic propofol (2,6-di-iso-propylphenol) is a known HCN1 allosteric inhibitor6 with unknown structural basis. Here, using single-particle cryo-electron microscopy and electrophysiology, we show that propofol inhibits HCN1 by binding to a mechanistic hotspot in a groove between the S5 and S6 transmembrane helices. We found that propofol restored voltage-dependent closing in two HCN1 epilepsy-associated polymorphisms that act by destabilizing the channel closed state: M305L, located in the propofol-binding site in S5, and D401H in S6 (refs. 7,8). To understand the mechanism of propofol inhibition and restoration of voltage-gating, we tracked voltage-sensor movement in spHCN channels and found that propofol inhibition is independent of voltage-sensor conformational changes. Mutations at the homologous methionine in spHCN and an adjacent conserved phenylalanine in S6 similarly destabilize closing without disrupting voltage-sensor movements, indicating that voltage-dependent closure requires this interface intact. We propose a model for voltage-dependent gating in which propofol stabilizes coupling between the voltage sensor and pore at this conserved methionine-phenylalanine interface in HCN channels. These findings unlock potential exploitation of this site to design specific drugs targeting HCN channelopathies.

A pentameric TRPV3 channel with a dilated pore.

Transient receptor potential (TRP) channels are a large, eukaryotic ion channel superfamily that control diverse physiological functions, and therefore are attractive drug targets1-5. More than 210 structures from more than 20 different TRP channels have been determined, and all are tetramers4. Despite this wealth of structures, many aspects concerning TRPV channels remain poorly understood, including the pore-dilation phenomenon, whereby prolonged activation leads to increased conductance, permeability to large ions and loss of rectification6,7. Here, we used high-speed atomic force microscopy (HS-AFM) to analyse membrane-embedded TRPV3 at the single-molecule level and discovered a pentameric state. HS-AFM dynamic imaging revealed transience and reversibility of the pentamer in dynamic equilibrium with the canonical tetramer through membrane diffusive protomer exchange. The pentamer population increased upon diphenylboronic anhydride (DPBA) addition, an agonist that has been shown to induce TRPV3 pore dilation. On the basis of these findings, we designed a protein production and data analysis pipeline that resulted in a cryogenic-electron microscopy structure of the TRPV3 pentamer, showing an enlarged pore compared to the tetramer. The slow kinetics to enter and exit the pentameric state, the increased pentamer formation upon DPBA addition and the enlarged pore indicate that the pentamer represents the structural correlate of pore dilation. We thus show membrane diffusive protomer exchange as an additional mechanism for structural changes and conformational variability. Overall, we provide structural evidence for a non-canonical pentameric TRP-channel assembly, laying the foundation for new directions in TRP channel research.

Footprint evidence of early hominin locomotor diversity at Laetoli, Tanzania.

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage1-3. Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity3-5. In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli.

Large Clusters of Invasive emm49 Group A Streptococcus Identified Within Arizona Health Care Facilities Through Statewide Genomic Surveillance System, 2019-2021.

A statewide genomic surveillance system for invasive Group A Streptococcus was implemented in Arizona in June 2019, resulting in 1046 isolates being submitted for genomic analysis to characterize emm types and identify transmission clusters. Eleven of the 32 identified distinct emm types comprised >80% of samples, with 29.7% of all isolates being typed as emm49 (and its genetic derivative emm151). Phylogenetic analysis initially identified an emm49 genomic cluster of 4 isolates that rapidly expanded over subsequent months (June 2019 to February 2020). Public health investigations identified epidemiologic links with 3 different long-term care facilities, resulting in specific interventions. Unbiased genomic surveillance allowed for identification and response to clusters that would have otherwise remained undetected.

Cognitive household labor: gender disparities and consequences for maternal mental health and wellbeing.

PURPOSE: Although the division of unpaid household labor has been studied as a driver of global gender inequity, the cognitive dimension of household labor-planning, anticipating, and delegating household tasks-has received less empirical investigation. Cognitive household labor represents a form of invisible and often unacknowledged domestic work that has been challenging to measure. METHODS: Within 322 mothers of young children, we assessed the division of both cognitive ("planning") and physical ("execution") household labor within 30 common household tasks using a self-report measure. RESULTS: We found that while mothers did more of the overall domestic labor than their partners, the division of cognitive labor was particularly gendered, such that women's share of cognitive labor was more disproportionate than physical household labor. We found that cognitive labor was associated with women's depression, stress, burnout, overall mental health, and relationship functioning. CONCLUSIONS: This study is one of the first to investigate cognitive labor quantitatively, and the first to investigate cognitive and physical dimensions within the same household tasks. Understanding how cognitive labor affects mothers' mental wellbeing has important implications for both practice and policy.

Retaining Interest in Child and Adolescent Psychiatry Among General Residency Trainees.

OBJECTIVES: This study aimed to identify factors affecting current general psychiatry residents' interest in child and adolescent psychiatry (CAP) at Lehigh Valley Health Network (LVHN). Furthermore, it aimed to identify areas for improvement in clinical education to address the shortage of child psychiatrists at the institution at the time of this study. METHODS: An electronic anonymous pre-implementation survey was sent to all the current general psychiatry residents at LVHN. It assessed the most important factors for trainees in deciding their career paths into CAP, their comfort level with children and families, and overall CAP and related systems-based knowledge. Interventions based on the survey results were implemented in the LVHN psychiatry residency program. The residents then completed a post-intervention survey to assess the impact of these interventions on their perspectives toward CAP. RESULTS: CAP rotation experience and work with families were strong influencers for general psychiatry residents at LVHN in pursing CAP. Systems-based knowledge was particularly lacking compared to overall CAP knowledge. Educational interventions that were implemented at LVHN led to improvements in residents' sense of competence working with children and families with no net loss of interest in CAP. CONCLUSIONS: Educational modifications enhanced attitudes toward CAP among LVHN general psychiatry residents. Implementing such modifications at other residency programs may be likewise effective in retaining interest in CAP among their general psychiatry residents.

Tbx18 Orchestrates Cytostructural Transdifferentiation of Cardiomyocytes to Pacemaker Cells by Recruiting the Epithelial-Mesenchymal Transition Program.

Previously, we reported that heterologous expression of an embryonic transcription factor, Tbx18, reprograms ventricular cardiomyocytes into induced pacemaker cells (Tbx18-iPMs), though the key pathways are unknown. Here, we have used a tandem mass tag proteomic approach to characterize the impact of Tbx18 on neonatal rat ventricular myocytes. Tbx18 expression triggered vast proteome remodeling. Tbx18-iPMs exhibited increased expression of known pacemaker ion channels, including Hcn4 and Cx45 as well as upregulation of the mechanosensitive ion channels Piezo1, Trpp2 (PKD2), and TrpM7. Metabolic pathways were broadly downregulated, as were ion channels associated with ventricular excitation-contraction coupling. Tbx18-iPMs also exhibited extensive intracellular cytoskeletal and extracellular matrix remodeling, including 96 differentially expressed proteins associated with the epithelial-to-mesenchymal transition (EMT). RNAseq extended coverage of low abundance transcription factors, revealing upregulation of EMT-inducing Snai1, Snai2, Twist1, Twist2, and Zeb2. Finally, network diffusion mapping of >200 transcriptional regulators indicates EMT and heart development factors occupy adjacent network neighborhoods downstream of Tbx18 but upstream of metabolic control factors. In conclusion, transdifferentiation of cardiac myocytes into pacemaker cells entails massive electrogenic, metabolic, and cytostructural remodeling. Structural changes exhibit hallmarks of the EMT. The results aid ongoing efforts to maximize the yield and phenotypic stability of engineered biological pacemakers.

Persistent Ascaris Transmission Is Possible in Urban Areas Even Where Sanitation Coverage Is High.

In low-income, urban, informal communities lacking sewerage and solid waste services, onsite sanitation (sludges, aqueous effluent) and child feces are potential sources of human fecal contamination in living environments. Working in informal communities of urban Maputo, Mozambique, we developed a quantitative, stochastic, mass-balance approach to evaluate plausible scenarios of localized contamination that could explain why the soil-transmitted helminth Ascaris remains endemic despite nearly universal coverage of latrines that sequester most fecal wastes. We used microscopy to enumerate presumptively viable Ascaris ova in feces, fecal sludges, and soils from compounds (i.e., household clusters) and then constructed a steady-state mass-balance model to evaluate possible contamination scenarios capable of explaining observed ova counts in soils. Observed Ascaris counts (mean = -0.01 log10 ova per wet gram of soil, sd = 0.71 log10) could be explained by deposits of 1.9 grams per day (10th percentile 0.04 grams, 90th percentile 84 grams) of child feces on average, rare fecal sludge contamination events that transport 17 kg every three years (10th percentile 1.0 kg, 90th percentile 260 kg), or a daily discharge of 2.7 kg aqueous effluent from an onsite system (10th percentile 0.09 kg, 90th percentile 82 kg). Results suggest that even limited intermittent flows of fecal wastes in this setting can result in a steady-state density of Ascaris ova in soils capable of sustaining transmission, given the high prevalence of Ascaris shedding by children (prevalence = 25%; mean = 3.7 log10 per wet gram, sd = 1.1 log10), the high Ascaris ova counts in fecal sludges (prevalence = 88%; mean = 1.8 log10 per wet gram, sd = 0.95 log10), and the extended persistence and viability of Ascaris ova in soils. Even near-universal coverage of onsite sanitation may allow for sustained transmission of Ascaris under these conditions.

Minimally invasive biomarkers in human and non-human primate evolutionary biology: Tools for understanding variation and adaptation.

BACKGROUND: The use of minimally invasive biomarkers (MIBs - physiological biomarkers obtained from minimally invasive sample types) has expanded rapidly in science and medicine over the past several decades. The MIB approach is a methodological strength in the field of human and non-human primate evolutionary biology (HEB). Among humans and our closest relatives, MIBs provide unique opportunities to document phenotypic variation and to operationalize evolutionary hypotheses. AIMS: This paper overviews the use of MIBs in HEB. Our objectives are to (1) highlight key research topics which successfully implement MIBs, (2) identify promising yet under-investigated areas of MIB application, and (3) discuss current challenges in MIB research, with suggestions for advancing the field. DISCUSSION AND CONCLUSIONS: A range of MIBs are used to investigate focal topics in HEB, including energetics and life history variation/evolution, developmental plasticity, and social status and dominance relationships. Nonetheless, we identify gaps in existing MIB research on traits such as physical growth and gut function that are central to the field. Several challenges remain for HEB research using MIBs, including the need for additional biomarkers and methods of assessment, robust validations, and approaches that are standardized across labs and research groups. Importantly, researchers must provide better support for adaptation and fitness effects in hypothesis testing (e.g., by obtaining complementary measures of energy expenditure, demonstrating redundancy of function, and performing lifetime/longitudinal analyses). We point to continued progress in the use of MIBs in HEB to better understand the past, present, and future of humans and our closest primate relatives.

Cardiac microstructural alterations in immune-inflammatory myocardial disease: a retrospective case-control study.

BACKGROUND: Immune-inflammatory myocardial disease contributes to multiple chronic cardiac processes, but access to non-invasive screening is limited. We have previously developed a method of echocardiographic texture analysis, called the high-spectrum signal intensity coefficient (HS-SIC) which assesses myocardial microstructure and previously associated with myocardial fibrosis. We aimed to determine whether this echocardiographic texture analysis of cardiac microstructure can identify inflammatory cardiac disease in the clinical setting. METHODS: We conducted a retrospective case-control study of 318 patients with distinct clinical myocardial pathologies and 20 healthy controls. Populations included myocarditis, atypical chest pain/palpitations, STEMI, severe aortic stenosis, acute COVID infection, amyloidosis, and cardiac transplantation with acute rejection, without current rejection but with prior rejection, and with no history of rejection. We assessed the HS-SIC's ability to differentiate between a broader diversity of clinical groups and healthy controls. We used Kruskal-Wallis tests to compare HS-SIC values measured in each of the clinical populations with those in the healthy control group and compared HS-SIC values between the subgroups of cardiac transplantation rejection status. RESULTS: For the total sample of N = 338, the mean age was 49.6 ± 20.9 years and 50% were women. The mean ± standard error of the mean of HS-SIC were: 0.668 ± 0.074 for controls, 0.552 ± 0.049 for atypical chest pain/palpitations, 0.425 ± 0.058 for myocarditis, 0.881 ± 0.129 for STEMI, 1.116 ± 0.196 for severe aortic stenosis, 0.904 ± 0.116 for acute COVID, and 0.698 ± 0.103 for amyloidosis. Among cardiac transplant recipients, HS-SIC values were 0.478 ± 0.999 for active rejection, 0.594 ± 0.091 for prior rejection, and 1.191 ± 0.442 for never rejection. We observed significant differences in HS-SIC between controls and myocarditis (P = 0.0014), active rejection (P = 0.0076), and atypical chest pain or palpitations (P = 0.0014); as well as between transplant patients with active rejection and those without current or prior rejection (P = 0.031). CONCLUSIONS: An echocardiographic method can be used to characterize tissue signatures of microstructural changes across a spectrum of cardiac disease including immune-inflammatory conditions.

Canonical Wnt signaling promotes pacemaker cell specification of cardiac mesodermal cells derived from mouse and human embryonic stem cells.

Cardiac differentiation of embryonic stem cells (ESCs) can give rise to de novo chamber cardiomyocytes and nodal pacemaker cells. Compared with our understanding of direct differentiation toward atrial and ventricular myocytes, the mechanisms for nodal pacemaker cell commitment are not well understood. Taking a cue from the prominence of canonical Wnt signaling during cardiac pacemaker tissue development in chick embryos, we asked if modulations of Wnt signaling influence cardiac progenitors to bifurcate to either chamber cardiomyocytes or pacemaker cells. Omitting an exogenous Wnt inhibitor, which is routinely added to maximize cardiac myocyte yield during differentiation of mouse and human ESCs, led to increased yield of spontaneously beating cardiomyocytes with action potential properties similar to those of native sinoatrial node pacemaker cells. The pacemaker phenotype was accompanied by enhanced expression of genes and gene products that mark nodal pacemaker cells such as Hcn4, Tbx18, Tbx3, and Shox2. Addition of exogenous Wnt3a ligand, which activates canonical Wnt/ß-catenin signaling, increased the yield of pacemaker-like myocytes while reducing cTNT-positive pan-cardiac differentiation. Conversely, addition of inhibitors of Wnt/ß-catenin signaling led to increased chamber myocyte lineage development at the expense of pacemaker cell specification. The positive impact of canonical Wnt signaling on nodal pacemaker cell differentiation was evidenced in direct differentiation of two human ESC lines and human induced pluripotent stem cells. Our data identify the Wnt/ß-catenin pathway as a critical determinant of cardiac myocyte subtype commitment during ESC differentiation: endogenous Wnt signaling favors the pacemaker lineage, whereas its suppression promotes the chamber cardiomyocyte lineage.

Stem Cell Composition of Umbilical Cord Blood Following Milking Compared with Delayed Clamping of the Cord Appears Better Suited for Promoting Hematopoiesis.

In comparing placental transfusion strategies, blood obtained from an umbilical cord that has been "milked" vs one in which clamping was simply delayed contains mesenchymal stromal cells in addition to solely hematopoietic stem cells, a composition more favorable for hematopoiesis, as suggested by its superior rescue of lethally irradiated bone marrow-depleted mice.

Decriminalization in action: lessons from the Los Angeles model.

Los Angeles County's Office of Diversion and Reentry (ODR) has removed over 3800 people from the largest jail system in the country. Across various diversion programs, ODR's fundamental goal is to provide permanent, lifetime care for each diverted person. This article describes ODR's various diversion programs, and elucidates the types of elaborate clinical and court-related interventions that are necessary to remove persons with serious mental disorders from jail custody. As Los Angeles continues to build the necessary community-based continuum of mental health care, ODR's model proves that thoughtfully removing persons with serious mental disorders from jail is possible and necessary for the health of both patients and community.

Comparison of Nitroglycerin and Terbutaline for External Cephalic Version in Women Who Received Neuraxial Anesthesia: A Retrospective Analysis.

External cephalic version is a technique that decreases the need for cesarean delivery in patients with breech presentation. Several techniques exist to increase the success of external cephalic version; however, there are no studies comparing different tocolytics in patients who also received neuraxial anesthesia. We, therefore, performed a review of 198 patients who presented for external cephalic version and compared their success rates based on the tocolytic medication utilized. The external cephalic version success rate for patients who received terbutaline was significantly higher than for those who received nitroglycerin (N [%]: 57 [65.6] terbutaline group versus 40 [36.0] nitroglycerin group; P < .001).

Utilization of a Voice-Based Virtual Reality Advanced Cardiac Life Support Team Leader Refresher: Prospective Observational Study.

BACKGROUND: The incidence of cardiac arrests per year in the United States continues to increase, yet in-hospital cardiac arrest survival rates significantly vary between hospitals. Current methods of training are expensive, time consuming, and difficult to scale, which necessitates improvements in advanced cardiac life support (ACLS) training. Virtual reality (VR) has been proposed as an alternative or adjunct to high-fidelity simulation (HFS) in several environments. No evaluations to date have explored the ability of a VR program to examine both technical and behavioral skills and demonstrate a cost comparison. OBJECTIVE: This study aimed to explore the utility of a voice-based VR ACLS team leader refresher as compared with HFS. METHODS: This prospective observational study performed at an academic institution consisted of 25 postgraduate year 2 residents. Participants were randomized to HFS or VR training and then crossed groups after a 2-week washout. Participants were graded on technical and nontechnical skills. Participants also completed self-assessments about the modules. Proctors were assessed for fatigue and task saturation, and cost analysis based on local economic data was performed. RESULTS: A total of 23 of 25 participants were included in the scoring analysis. Fewer participants were familiar with VR compared with HFS (9/25, 36% vs 25/25, 100%; P<.001). Self-reported satisfaction and utilization scores were similar; however, significantly more participants felt HFS provided better feedback: 99 (IQR 89-100) vs 79 (IQR 71-88); P<.001. Technical scores were higher in the HFS group; however, nontechnical scores for decision making and communication were not significantly different between modalities. VR sessions were 21 (IQR 19-24) min shorter than HFS sessions, the National Aeronautics and Space Administration task load index scores for proctors were lower in each category, and VR sessions were estimated to be US $103.68 less expensive in a single-learner, single-session model. CONCLUSIONS: Utilization of a VR-based team leader refresher for ACLS skills is comparable with HFS in several areas, including learner satisfaction. The VR module was more cost-effective and was easier to proctor; however, HFS was better at delivering feedback to participants. Optimal education strategies likely contain elements of both modalities. Further studies are needed to examine the utility of VR-based environments at scale.

Effectiveness of a Tailored Intervention for Women With Attention Deficit Hyperactivity Disorder (ADHD) and ADHD Symptoms: A Randomized Controlled Study.

IMPORTANCE: Women with attention deficit hyperactivity disorder (ADHD) and ADHD symptoms may experience difficulty carrying out desired life roles and activities. OBJECTIVE: To determine whether a 7-wk tailored occupation-based intervention can reduce perceived stress and ADHD symptoms and enhance perceived performance of and satisfaction with daily roles and activities among women with ADHD. DESIGN: Randomization to intervention (n = 11) and control (n = 12) groups. SETTING: Home and community. PARTICIPANTS: Twenty-three participants ages 20-55 yr, English speaking, and with a self-reported diagnosis of ADHD. INTERVENTION: The intervention was administered for 7 wk in individual 1-hr sessions and addressed routine establishment, organization, time management, stress management, and sensory regulation in the home and community. OUTCOMES AND MEASURES: Adult Attention Deficit Hyperactivity Disorder Self-Report Scale, Perceived Stress Scale, and Canadian Occupational Performance Measure. RESULTS: At 1-wk postintervention, statistically significant differences were found between intervention and control groups in perceived stress (Z = -3.838, p < .000, d = -2.66), ADHD symptoms (Z = -3.605, p < .000, d = -2.17), and COPM Performance (Z = -4.074, p < .000, d = 3.04) and Satisfaction change scores (Z = -3.759, p < .000, d = 2.82). CONCLUSION AND RELEVANCE: A 7-wk tailored intervention reduced perceived stress and ADHD symptoms and enhanced perceived performance of and satisfaction with desired occupational roles and activities in a sample of women with ADHD. Further research is warranted to determine whether the intervention can be useful to women with ADHD beyond the present sample. WHAT THIS ARTICLE ADDS: This intervention may offer an effective nonpharmacological option for women with ADHD symptoms.

Acute neuropathological consequences of short-term mechanical ventilation in wild-type and Alzheimer's disease mice.

BACKGROUND: Mechanical ventilation is strongly associated with cognitive decline after critical illness. This finding is particularly evident among older individuals who have pre-existing cognitive impairment, most commonly characterized by varying degrees of cerebral amyloid-ß accumulation, neuroinflammation, and blood-brain barrier dysfunction. We sought to test the hypothesis that short-term mechanical ventilation contributes to the neuropathology of cognitive impairment by (i) increasing cerebral amyloid-ß accumulation in mice with pre-existing Alzheimer's disease pathology, (ii) increasing neurologic and systemic inflammation in wild-type mice and mice with pre-existing Alzheimer's disease pathology, and (iii) increasing hippocampal blood-brain barrier permeability in wild-type mice and mice with pre-existing Alzheimer's disease pathology. METHODS: We subjected double transgenic Alzheimer's disease (APP/PSEN1) and wild-type mice to mechanical ventilation for 4 h and compared to non-mechanically ventilated Alzheimer's disease model and wild-type mice. Cerebral soluble/insoluble amyloid-ß1-40/amyloid-ß1-42 and neurological and systemic markers of inflammation were quantified. Hippocampal blood-brain barrier permeability was quantified using a novel methodology that enabled assessment of small and large molecule permeability across the blood-brain barrier. RESULTS: Mechanical ventilation resulted in (i) a significant increase in cerebral soluble amyloid-ß1-40 (p = 0.007) and (ii) significant increases in neuroinflammatory cytokines in both wild-type and Alzheimer's disease mice which, in most cases, were not reflected in the plasma. There were (i) direct correlations between polymorphonuclear cells in the bronchoalveolar fluid and cerebral soluble amyloid-ß1-40 (p = 0.0033), and several Alzheimer's disease-relevant neuroinflammatory biomarkers including cerebral TNF-α and IL-6; (iii) significant decreases in blood-brain barrier permeability in mechanically ventilated Alzheimer's disease mice and a trend towards increased blood-brain barrier permeability in mechanically ventilated wild-type mice. CONCLUSIONS: These results provide the first evidence that short-term mechanical ventilation independently promotes the neuropathology of Alzheimer's disease in subjects with and without pre-existing cerebral Alzheimer's disease pathology. Future studies are needed to further clarify the specific mechanisms by which this occurs and to develop neuroprotective mechanical ventilation strategies that mitigate the risk of cognitive decline after critical illness.

Comparison of cardiovascular effects of crizotinib and chemotherapy in ALK-positive advanced non-small-cell lung cancer.

AIM: We analyzed cardiac function in two Phase III studies of previously treated (PROFILE 1007) or untreated (PROFILE 1014) ALK-positive advanced non-small-cell lung cancer. PATIENTS & METHODS: Adverse events associated with cardiac failure were compared between treatment arms in each study separately. Cardiac function was assessed prospectively by multigated acquisition scans or echocardiograms. RESULTS: In PROFILE 1007 and 1014, incidence of cardiac failure adverse events was 0% (crizotinib) versus 0.6% (chemotherapy) and 2.3% versus 0.6%, respectively. In crizotinib versus chemotherapy arms, respectively, >20% left ventricular ejection fraction decreases occurred in 0/19 (0%) versus 1/16 (6.3%) patients from PROFILE 1007 and 4/150 (2.7%) versus 10/150 (6.7%) patients from PROFILE 1014. CONCLUSION: These analyses did not reveal any clinically meaningful changes in myocardial function with crizotinib in patients with ALK-positive non-small-cell lung cancer. Clinicaltrials.gov identifier: PROFILE 1007, NCT00932893; PROFILE 1014, NCT01154140.

Nanoparticle and Laminar Structured Lead Selenide Photoconductive Thin Film.

Lead selenide thin films composed of nanoparticles and laminar structures were deposited on glass substrates by a chemical bath deposition technique, and then thermally oxidized in oxygen atmosphere at an annealing temperature of 400 °C for 20 min. The particles and laminar structures deposited were randomly dispersed and well crystalized according to the hexagonal structure with the preferential orientation (200). The energy dispersive spectrum analysis confirms that the heat treatment introduced oxygen elements into the thin film while reducing the amount of iodine and selenium. The structural, surface morphological and electrical properties of the thin film were determined using various techniques including X-ray diffraction, scanning electron microscopy, and energy dispersive and X-ray analysis. A 3×3 mm² sized photoconductive detector was patterned, and its IR response under a blackbody radiation was also discussed.

Preschoolers exhibit conformity to computer-simulated food portion selection behaviors of remote peers.

Children have been found to rely on others for food choice and food intake cues, but it is unclear whether a similar type of social modeling occurs for food portion selection, especially among young children. Given that portion size predicts energy intake, it is important to understand the role of social influence on portion selection behavior early in life. The present study aimed to determine preschoolers' conformity to food portion selection patterns of remote peers using a computerized Portion Selection Task and examined the role of parents' feeding styles in children's susceptibility to others' food portion choices. Seventy-five 3-6 year old Singaporean children (M = 62 ±â€¯0.72 months) were asked to make food portion selections of high-energy-density (ED) foods and low-ED foods both independently and after having viewed remote peers' portion selections of the same foods. In the unhealthy peers condition, children saw peers choose large portions of high-ED foods and small portions of low-ED foods, while in the healthy peers condition, children saw peers select large portions of low-ED foods and small portions of high-ED foods. Parents were surveyed about their child feeding practices. Results revealed that participants exhibited conformity to the portion sizes of remote peers for both high-ED and low-ED foods under the healthy peers condition, but only marginally for high-ED foods under the unhealthy peers condition. Parents' higher restriction of foods for child's health was marginally associated with lower conformity to peers' portion selections of unhealthy foods and higher conformity to peers' portion selections of healthy foods. This study provides support for social modeling of food portion selection among young children, but the extent of social modeling may be contingent on characteristics of the food.