Individuation Revisited: Implications for Parent Education

Researchers have suggested that adolescents\u27 increase in autonomy is accompanied by maintaining close relations with parents. In this article, we explore this process of individuation from the perspective of mothers. Nearly 900 (n=878) white mothers of children aged 2 to 14 were interviewed via the telephone about their child\u27s independence and their perception of parent-child connectedness. Analyses revealed that from the perspective of mothers, while independence increased across childhood, parent-child connectedness decreased. These data suggest the need to support parents in remaining connected to their children as they enter adolescence. Implications of these findings for parent education are considered

Janus monolayers of transition metal dichalcogenides.

Structural symmetry-breaking plays a crucial role in determining the electronic band structures of two-dimensional materials. Tremendous efforts have been devoted to breaking the in-plane symmetry of graphene with electric fields on AB-stacked bilayers or stacked van der Waals heterostructures. In contrast, transition metal dichalcogenide monolayers are semiconductors with intrinsic in-plane asymmetry, leading to direct electronic bandgaps, distinctive optical properties and great potential in optoelectronics. Apart from their in-plane inversion asymmetry, an additional degree of freedom allowing spin manipulation can be induced by breaking the out-of-plane mirror symmetry with external electric fields or, as theoretically proposed, with an asymmetric out-of-plane structural configuration. Here, we report a synthetic strategy to grow Janus monolayers of transition metal dichalcogenides breaking the out-of-plane structural symmetry. In particular, based on a MoS2 monolayer, we fully replace the top-layer S with Se atoms. We confirm the Janus structure of MoSSe directly by means of scanning transmission electron microscopy and energy-dependent X-ray photoelectron spectroscopy, and prove the existence of vertical dipoles by second harmonic generation and piezoresponse force microscopy measurements

Integrity of H1 helix in prion protein revealed by molecular dynamic simulations to be especially vulnerable to changes in the relative orientation of H1 and its S1 flank

In the template-assistance model, normal prion protein (PrPC), the pathogenic cause of prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrPSc) through an autocatalytic process triggered by a transient interaction between PrPC and PrPSc. Conventional studies suggest the S1-H1-S2 region in PrPC to be the template of S1-S2 $\beta$-sheet in PrPSc, and the conformational conversion of PrPC into PrPSc may involve an unfolding of H1 in PrPC and its refolding into the $\beta$-sheet in PrPSc. Here we conduct a series of simulation experiments to test the idea of transient interaction of the template-assistance model. We find that the integrity of H1 in PrPC is vulnerable to a transient interaction that alters the native dihedral angles at residue Asn$^{143}$, which connects the S1 flank to H1, but not to interactions that alter the internal structure of the S1 flank, nor to those that alter the relative orientation between H1 and the S2 flank.Comment: A major revision on statistical analysis method has been made. The paper now has 23 pages, 11 figures. This work was presented at 2006 APS March meeting session K29.0004 at Baltimore, MD, USA 3/13-17, 2006. This paper has been accepted for pubcliation in European Biophysical Journal on Feb 2, 200

Pulmonary Tuberculosis and Delay in Anti-Tuberculous Treatment Are Important Risk Factors for Chronic Obstructive Pulmonary Disease

OBJECTIVE: Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database. MAIN OUTCOME MEASURES: Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment. RESULTS: The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768-2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD. CONCLUSIONS: Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients

457 KEYNOTE-495/KeyImPaCT: interim analysis of a randomized, biomarker-directed, phase 2 trial of pembrolizumab-based combination therapy for non–small cell lung cancer (NSCLC)

BackgroundT-cell–inflamed gene expression profile (TcellinfGEP) and tumor mutational burden (TMB) are clinically validated biomarkers that independently predict pembrolizumab response. This study investigated prospective TcellinfGEP and TMB assessment in evaluating first-line pembrolizumab-based combination therapies; the different treatment combinations evaluated may provide insight into the unique biology of each biomarker subgroup.MethodsKEYNOTE-495/KeyImPaCT is a group-sequential, adaptively randomized, multisite, open-label, phase 2 study investigating first-line pembrolizumab plus the VEGF/FGFR inhibitor lenvatinib, CTLA-4 inhibitor quavonlimab (MK-1308), or LAG-3 inhibitor favezelimab (MK-4280) in patients with advanced NSCLC. DNA and RNA were extracted from tumor tissue to determine TcellinfGEP and TMB; patients were assigned to one of four biomarker-defined subgroups (TcellinfGEPlowTMBlow, TcellinfGEPlowTMBhigh, TcellinfGEPhighTMBlow, TcellinfGEPhighTMBhigh) and randomly assigned 1:1:1 to receive pembrolizumab (200mg IV Q3W)+lenvatinib (20mg oral QD), pembrolizumab+quavonlimab (75mg IV Q6W), or pembrolizumab+favezelimab (200mg [n=30] or 800mg [n=34] Q3W; the initial prespecified dose was 200mg but changed to 800mg based on emerging data). The primary end point was investigator-assessed ORR per RECIST v1.1. Multiple interim analyses will be performed until the prespecified clinical signal is observed. The first interim analysis for each combination therapy occurred after ≥10 patients had ≥12 weeks of follow-up.ResultsAt the data cutoff (January 11, 2021), 208 patients were treated (pembrolizumab+lenvatinib, n=72; pembrolizumab+quavonlimab, n=72; pembrolizumab+favezelimab 200mg, n=30; pembrolizumab+favezelimab 800mg, n=34). The overall assay success rate for testing and determining TcellinfGEP and TMB was 94%. In patients treated with pembrolizumab+lenvatinib, pembrolizumab+quavonlimab, or pembrolizumab+favezelimab, ORRs were generally highest in the TcellinfGEPhighTMBhigh subgroup (table 1); response rates were similar across combinations within this subgroup. ORR was low across combinations within the TcellinfGEPlowTMBlow subgroup. Treatment-related adverse events (TRAEs) occurred in 88%, 65%, 57%, and 59% of patients in the pembrolizumab+lenvatinib, pembrolizumab+quavonlimab, pembrolizumab+favezelimab 200mg and pembrolizumab+favezelimab 800mg arms, respectively. Consistent with the known TRAEs of these agents, most TRAEs were grade 1 or 2 in severity except in the pembrolizumab+lenvatinib arm (grade 3–5, 63%). Three deaths from TRAEs occurred (pembrolizumab+lenvatinib [n=2], brain hemorrhage and myocardial infarction; pembrolizumab+favezelimab 800 mg [n=1], pneumonitis).Abstract 457 Table 1Confirmed ORR by Therapy and Biomarker StatusConclusionsThese data demonstrate the feasibility and clinical usefulness of prospective TcellinfGEP and TMB assessment to study the clinical activity of three first-line pembrolizumab-based combination therapies in patients with advanced NSCLC. Although sample sizes were small, the TcellinfGEPhighTMBhigh subgroup demonstrated the best response among the biomarker subgroups for all three combination therapies; further validation is needed to determine additional signals and may be addressed as more mature data become available.AcknowledgementsJeanne Fahey, PhD, of Merck & Co., Inc., Kenilworth, New Jersey, USA, provided critical review of the abstract. Elisha Dettman PhD, Mark Ayers MS, and Andrey Loboda PhD of Merck & Co., Inc., Kenilworth, New Jersey, USA, provided critical review of study translational data. Medical writing and/or editorial assistance was provided by Shane Walton, PhD, and Lei Bai, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicalTrials.gov, NCT03516981Ethics ApprovalThe study protocol and all amendments were approved by the relevant institutional review board or ethics committee at each study site. All patients provided written informed consent to participate in the clinical trial

Functional and Structural Characteristics of Tumor Angiogenesis in Lung Cancers Overexpressing Different VEGF Isoforms Assessed by DCE- and SSCE-MRI

The expressions of different vascular endothelial growth factor (VEGF) isoforms are associated with the degree of tumor invasiveness and the patient's prognosis in human cancers. We hypothesized that different VEGF isoforms can exert different effects on the functional and structural characteristics of tumor angiogenesis. We used dynamic contrast-enhanced MRI (DCE-MRI) and steady-state contrast-enhanced MRI (SSCE-MRI) to evaluate in vivo vascular functions (e.g., perfusion and permeability) and structural characteristics (e.g., vascular size and vessel density) of the tumor angiogenesis induced by different VEGF isoforms (VEGF121, VEGF165, and VEGF189) in a murine xenograft model of human lung cancer. Tumors overexpressing VEGF189 were larger than those overexpressing the other two VEGF isoforms. The Ktrans map obtained from DCE-MRI revealed that the perfusion and permeability functions of tumor microvessels was highest in both the rim and core regions of VEGF189-overexpressing tumors (p<0.001 for both tumor rim and core). The relative vessel density and relative vessel size indexes derived from SSCE-MRI revealed that VEGF189-overexpressing tumors had the smallest (p<0.05) and the most-dense (p<0.01) microvessels, which penetrated deeply from the tumor rim into the core, followed by the VEGF165-overepxressing tumor, whose microvessels were located mainly in the tumor rim. The lowest-density microvessels were found in the VEGF121-overexpressing tumor; these microvessels had a relatively large lumen and were found mainly in the tumor rim. We conclude that among the three VEGF isoforms evaluated, VEGF189 induces the most densely sprouting and smallest tumor microvessels with the highest in vivo perfusion and permeability functions. These characteristics of tumor microvessels may contribute to the reported adverse effects of VEGF189 overexpression on tumor progression, metastasis, and patient survival in several human cancers, including non-small cell lung cancer, and suggest that applying aggressive therapy may be necessary in human cancers in which VEGF189 is overexpressed

Presentations of patients of poisoning and predictors of poisoning-related fatality: Findings from a hospital-based prospective study

<p>Abstract</p> <p>Background</p> <p>Poisoning is a significant public health problem worldwide and is one of the most common reasons for visiting emergency departments (EDs), but factors that help to predict overall poisoning-related fatality have rarely been elucidated. Using 1512 subjects from a hospital-based study, we sought to describe the demographic and clinical characteristics of poisoning patients and to identify predictors for poisoning-related fatality.</p> <p>Methods</p> <p>Between January 2001 and December 2002 we prospectively recruited poisoning patients through the EDs of two medical centers in southwest Taiwan. Interviews were conducted with patients within 24 hours after admission to collect relevant information. We made comparisons between survival and fatality cases, and used logistic regressions to identify predictors of fatality.</p> <p>Results</p> <p>A total of 1512 poisoning cases were recorded at the EDs during the study period, corresponding to an average of 4.2 poisonings per 1000 ED visits. These cases involved 828 women and 684 men with a mean age of 38.8 years, although most patients were between 19 and 50 years old (66.8%), and 29.4% were 19 to 30 years. Drugs were the dominant poisoning agents involved (49.9%), followed by pesticides (14.5%). Of the 1512 patients, 63 fatalities (4.2%) occurred. Paraquat exposure was associated with an extremely high fatality rate (72.1%). The significant predictors for fatality included age over 61 years, insufficient respiration, shock status, abnormal heart rate, abnormal body temperature, suicidal intent and paraquat exposure.</p> <p>Conclusion</p> <p>In addition to well-recognized risk factors for fatality in clinical settings, such as old age and abnormal vital signs, we found that suicidal intent and ingestion of paraquat were significant predictors of poisoning-related fatality. Identification of these predictors may help risk stratification and the development of preventive interventions.</p

The Influences of H2Plasma Pretreatment on the Growth of Vertically Aligned Carbon Nanotubes by Microwave Plasma Chemical Vapor Deposition

The effects of H2flow rate during plasma pretreatment on synthesizing the multiwalled carbon nanotubes (MWCNTs) by using the microwave plasma chemical vapor deposition are investigated in this study. A H2and CH4gas mixture with a 9:1 ratio was used as a precursor for the synthesis of MWCNT on Ni-coated TaN/Si(100) substrates. The structure and composition of Ni catalyst nanoparticles were investigated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The present findings showed that denser Ni catalyst nanoparticles and more vertically aligned MWCNTs could be effectively achieved at higher flow rates. From Raman results, we found that the intensity ratio of G and D bands (ID/IG) decreases with an increasing flow rate. In addition, TEM results suggest that H2plasma pretreatment can effectively reduce the amorphous carbon and carbonaceous particles. As a result, the pretreatment plays a crucial role in modifying the obtained MWCNTs structures

Three New Structures of Left-Handed RadA Helical Filaments: Structural Flexibility of N-Terminal Domain Is Critical for Recombinase Activity

RecA family proteins, including bacterial RecA, archaeal RadA, and eukaryotic Dmc1 and Rad51, mediate homologous recombination, a reaction essential for maintaining genome integrity. In the presence of ATP, these proteins bind a single-strand DNA to form a right-handed nucleoprotein filament, which catalyzes pairing and strand exchange with a homologous double-stranded DNA (dsDNA), by as-yet unknown mechanisms. We recently reported a structure of RadA left-handed helical filament, and here present three new structures of RadA left-handed helical filaments. Comparative structural analysis between different RadA/Rad51 helical filaments reveals that the N-terminal domain (NTD) of RadA/Rad51, implicated in dsDNA binding, is highly flexible. We identify a hinge region between NTD and polymerization motif as responsible for rigid body movement of NTD. Mutant analysis further confirms that structural flexibility of NTD is essential for RadA's recombinase activity. These results support our previous hypothesis that ATP-dependent axial rotation of RadA nucleoprotein helical filament promotes homologous recombination