A k-shell decomposition method for weighted networks

We present a generalized method for calculating the k-shell structure of weighted networks. The method takes into account both the weight and the degree of a network, in such a way that in the absence of weights we resume the shell structure obtained by the classic k-shell decomposition. In the presence of weights, we show that the method is able to partition the network in a more refined way, without the need of any arbitrary threshold on the weight values. Furthermore, by simulating spreading processes using the susceptible-infectious-recovered model in four different weighted real-world networks, we show that the weighted k-shell decomposition method ranks the nodes more accurately, by placing nodes with higher spreading potential into shells closer to the core. In addition, we demonstrate our new method on a real economic network and show that the core calculated using the weighted k-shell method is more meaningful from an economic perspective when compared with the unweighted one.Comment: 17 pages, 6 figure

Clinicopathologic Risk Factor Distributions for MLH1 Promoter Region Methylation in CIMP-Positive Tumors

The CpG Island Methylator Phenotype (CIMP) is a major molecular pathway in colorectal cancer (CRC). Approximately 25% to 60% of CIMP tumors are microsatellite unstable (MSI-H) due to DNA hypermethylation of the MLH1 gene promoter. Our aim was to determine if the distributions of clinicopathologic factors in CIMP-positive tumors with MLH1 DNA methylation differed from those in CIMP-positive tumors without DNA methylation of MLH1

Dutch translation and cross-cultural validation of the Adult Social Care Outcomes Toolkit (ASCOT)

Background: The Adult Social Care Outcomes Toolkit was developed to measure outcomes of social care in England. In this study, we translated the four level self-completion version (SCT-4) of the ASCOT for use in the Netherlands and performed a cross-cultural validation. Methods: The ASCOT SCT-4 was translated into Dutch following international guidelines, including two forward and back translations. The resulting version was pilot tested among frail older adults using think-aloud interviews. Furthermore, using a subsample of the Dutch ACT-study, we investigated test-retest reliability and construct validity and compared response distributions with data from a comparable English study. Results: The pilot tests showed that translated items were in general understood as intended, that most items were reliable, and that the response distributions of the Dutch translation and associations with other measures were comparable to the original English version. Based on the results of the pilot tests, some small modifications and a revision of the Dignity items were proposed for the final translation, which were approved by the ASCOT development team. The complete original English version and the final Dutch translation can be obtained after registration on the ASCOT website (http://www.pssru.ac.uk/ascot). Conclusions: This study provides preliminary evidence that the Dutch translation of the ASCOT is valid, reliable and comparable to the original English version. We recommend further research to confirm the validity of the modified Dutch ASCOT translation

Effect of a Motivational Interviewing–Based Intervention on Initiation of Mental Health Treatment and Mental Health After an Emergency Department Visit Among Suicidal Adolescents

Abstract IMPORTANCE Emergency department (ED) visits present opportunities to identify and refer suicidal youth for outpatient mental health care, although this practice is not routine. OBJECTIVE To examine whether a motivational interviewing–based intervention increases linkage of adolescents to outpatient mental health services and reduces depression symptoms and suicidal ideation in adolescents seeking emergency care for non–mental health–related concerns who screen positive for suicide risk. DESIGN, SETTING, AND PARTICIPANTS In this randomized clinical trial, adolescents aged 12 to 17 years who screened positive on the Ask Suicide Screening Questions (ASQ) during a nonpsychiatric ED visit at 2 academic pediatric EDs in Ohio were recruited from April 2013 to July 2015. Intention-totreat analyses were performed from September 2018 to October 2019. INTERVENTIONS The Suicidal Teens Accessing Treatment After an Emergency Department Visit (STAT-ED) intervention included motivational interviewing to target family engagement, problem solving, referral assistance, and limited case management. The enhanced usual care (EUC) intervention consisted of brief mental health care consultation and referral. MAIN OUTCOMES AND MEASURES Primary outcomes were mental health treatment initiation and attendance within 2 months of ED discharge and suicidal ideation (assessed by the Suicidal Ideation Questionnaire JR) and depression symptoms (assessed by the Center for Epidemiologic Studies– Depression scale) at 2 and 6 months. Exploratory outcomes included treatment initiation and attendance and suicide attempts at 6 months. RESULTS A total of 168 participants were randomized and 159 included in the intention-to-treat analyses (mean [SD] age, 15.0 [1.5] years; 126 [79.2%] female; and 80 [50.3%] white). Seventy-nine participants were randomized to receive the STAT-ED intervention and 80 to receive EUC. At 2 months, youth in the STAT-ED group had similar rates of mental health treatment initiation compared with youth in the EUC group as assessed by parent report (29 [50.9%] vs 22 [34.9%]; adjusted odds ratio [OR], 2.08; 95% CI, 0.97-4.45) and administrative data from mental health care agencies (19 [29.7%] vs 11 [19.3%]; adjusted OR, 1.77; 95% CI, 0.76-4.15). At 2 months, youth in the STAT-ED group and the EUC group had similar rates of treatment attendance (1 appointment: 6 [9.7%] vs 2 [3.6%]; adjusted OR, 2.97; 95% CI, 0.56-15.73; 2 appointments: 10 [16.1%] vs 7 [12.7%]; adjusted OR, 1.43; 95% CI, 0.50-4.11). There were no significant group × time differences in suicidal ideation (F = 0.28; P = .72) and depression symptoms (F = 0.49; P = .60) during the 6-month follow-up period. In exploratory analyses, at 6 months, STAT-ED participants had significantly higher rates of agencyreported mental health treatment initiation (adjusted OR, 2.48; 95% CI, 1.16-5.28) and more completed appointments (t99.7 = 2.58; P = .01). CONCLUSIONS AND RELEVANCE This study’s findings indicate that no differences were found on any primary outcome by study condition. However, STAT-ED was more efficacious than EUC at increasing mental health treatment initiation and attendance at 6 months. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01779414 JAMA Network Open. 2019;2(12):e1917941. doi:10.1001/jamanetworkopen.2019.1794

The influence of thermal evolution in the magnetic protection of terrestrial planets

Magnetic protection of potentially habitable planets plays a central role in determining their actual habitability and/or the chances of detecting atmospheric biosignatures. Here we develop a thermal evolution model of potentially habitable Earth-like planets and super-Earths (SEs). Using up-to-date dynamo-scaling laws, we predict the properties of core dynamo magnetic fields and study the influence of thermal evolution on their properties. The level of magnetic protection of tidally locked and unlocked planets is estimated by combining simplified models of the planetary magnetosphere and a phenomenological description of the stellar wind. Thermal evolution introduces a strong dependence of magnetic protection on planetary mass and rotation rate. Tidally locked terrestrial planets with an Earth-like composition would have early dayside magnetopause distances between 1.5 and 4.0 Rp , larger than previously estimated. Unlocked planets with periods of rotation ~1 day are protected by magnetospheres extending between 3 and 8 Rp . Our results are robust in comparison with variations in planetary bulk composition and uncertainties in other critical model parameters. For illustration purposes, the thermal evolution and magnetic protection of the potentially habitable SEs GL 581d, GJ 667Cc, and HD 40307g were also studied. Assuming an Earth-like composition, we found that the dynamos of these planets are already extinct or close to being shut down. While GL 581d is the best protected, the protection of HD 40307g cannot be reliably estimated. GJ 667Cc, even under optimistic conditions, seems to be severely exposed to the stellar wind, and, under the conditions of our model, has probably suffered massive atmospheric losses

5D gravity and the discrepant G measurements

It is shown that 5D Kaluza-Klein theory stabilized by an external bulk scalar field may solve the discrepant laboratory G measurements. This is achieved by an effective coupling between gravitation and the geomagnetic field. Experimental considerations are also addressed.Comment: 13 pages, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The gravitational Constant. Generalized gravitational theories and experiments (30 April-10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, (Kluwer), 13pp. (in print) (2003

Infected Cell Killing by HIV-1 Protease Promotes NF-κB Dependent HIV-1 Replication

Acute HIV-1 infection of CD4 T cells often results in apoptotic death of infected cells, yet it is unclear what evolutionary advantage this offers to HIV-1. Given the independent observations that acute T cell HIV-1 infection results in (1) NF-κB activation, (2) caspase 8 dependent apoptosis, and that (3) caspase 8 directly activates NF-κB, we questioned whether these three events might be interrelated. We first show that HIV-1 infected T cell apoptosis, NF-κB activation, and caspase 8 cleavage by HIV-1 protease are coincident. Next we show that HIV-1 protease not only cleaves procaspase 8, producing Casp8p41, but also independently stimulates NF-κB activity. Finally, we demonstrate that the HIV protease cleavage of caspase 8 is necessary for optimal NF-κB activation and that the HIV-1 protease specific cleavage fragment Casp8p41 is sufficient to stimulate HIV-1 replication through NF-κB dependent HIV-LTR activation both in vitro as well as in cells from HIV infected donors. Consequently, the molecular events which promote death of HIV-1 infected T cells function dually to promote HIV-1 replication, thereby favoring the propagation and survival of HIV-1

Factor structure and construct validity of the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer)

Background: The ASCOT-Carer is a self-report instrument designed to measure social care-related quality of life (SCRQoL). This article presents the psychometric testing and validation of the ASCOT-Carer four response-level interview (INT4) in a sample of unpaid carers of adults who receive publicly-funded social care services in England. Methods: Unpaid carers were identified through a survey of users of publicly-funded social care services in England. 387 carers completed a face-to-face or telephone interview. Data on variables hypothesised to be related to SCRQoL (for example, characteristics of the carer, cared-for person and care situation) and measures of carer experience, strain, health-related quality of life and overall QoL were collected. Relationships between these variables and overall SCRQoL score were evaluated through correlation, ANOVA and regression analysis to test the construct validity of the scale. Internal reliability was assessed using Cronbach’s alpha and feasibility by the number of missing responses. Results: The construct validity was supported by statistically significant relationships between SCRQoL and scores on instruments of related constructs, as well as with characteristics of the carer and care recipient in univariate and multivariate analyses. A Cronbach’s alpha of 0.87 (7 items) indicates that the internal reliability of the instrument is satisfactory and a low number of missing responses (<1%) indicates a high level of acceptance. Conclusions: The results provide evidence to support the construct validity, factor structure, internal reliability and feasibility of the ASCOT-Carer INT4 as an instrument for measuring social care-related quality of life of unpaid carers who care for adults with a variety of long-term conditions, disability or problems related to old age

Pathway Analysis for Genome-Wide Association Study of Basal Cell Carcinoma of the Skin

Recently, a pathway-based approach has been developed to evaluate the cumulative contribution of the functionally related genes for genome-wide association studies (GWASs), which may help utilize GWAS data to a greater extent.In this study, we applied this approach for the GWAS of basal cell carcinoma (BCC) of the skin. We first conducted the BCC GWAS among 1,797 BCC cases and 5,197 controls in Caucasians with 740,760 genotyped SNPs. 115,688 SNPs were grouped into gene transcripts within 20 kb in distance and then into 174 Kyoto Encyclopedia of Genes and Genomes pathways, 205 BioCarta pathways, as well as two positive control gene sets (pigmentation gene set and BCC risk gene set). The association of each pathway with BCC risk was evaluated using the weighted Kolmogorov-Smirnov test. One thousand permutations were conducted to assess the significance.Both of the positive control gene sets reached pathway p-values<0.05. Four other pathways were also significantly associated with BCC risk: the heparan sulfate biosynthesis pathway (p  =  0.007, false discovery rate, FDR  =  0.35), the mCalpain pathway (p  =  0.002, FDR  =  0.12), the Rho cell motility signaling pathway (p  =  0.011, FDR  =  0.30), and the nitric oxide pathway (p  =  0.022, FDR  =  0.42).We identified four pathways associated with BCC risk, which may offer new insights into the etiology of BCC upon further validation, and this approach may help identify potential biological pathways that might be missed by the standard GWAS approach