Psychometric testing of three Chinese online-related addictive behavior instruments among Hong Kong university students

Objective: To validate the Chinese version of the nine-item Internet Gaming Disorder Scales- Short Form (IGDS-SF9), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application-Based Addiction Scale (SABAS) among Hong Kong university students. Participants and Methods: Participants aged between 17 and 30 years participated in the present study (n=307; 32.4% males; mean [SD] age=21.64 [8.11]). All the participants completed the IGDS-SF9, BSMAS, SABAS, and the Hospital Anxiety and Depression Scale (HADS). Confirmatory factor analyses (CFAs) were used to examine the factorial structures and the unidimensionality for IGDS-SF9, BSMAS, and SABAS. Results: CFAs demonstrated that the three scales were all unidimensional with satisfactory fit indices: comparative fit index = 0.969 to 0.992. In addition, the IGDS-SF9 and BSMAS were slightly modified based on the modification index in CFA. Conclusions: The Chinese IGDS-SF9, BSMAS, and SABAS are valid instruments to assess the addiction levels of internet-related activities for Hong Kong university students

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications

EFFICACY OF PNEUMATIC DILATATION FOR THE TREATMENT OF IDIOPATIC ACHALASIA: A SINGLE-CENTRE EXPERIENCE

Pneumatic dilatation (PD) and surgical miotomy (SM) are presentely the best treastments for untreated achalasia, with similar efficacy. There is no information on the relative efficacy of PD in younger compared to older patients. Aim of our study was to compare success rate and safety of PD patients under fifty years old in our Unit with graded PD under fluoroscopic view. Five male and 15 female with a median age of 47 years were treated. Twelve patients were less than fifthy years old (group I) while 8 were older (group II). Median dysphagia questionnaire score was 14 and 13 in group I and II respectively. Technical success was achieved in all patients. Seven patients were previously treated through other techniques. In group I all patients achieved a complete remission of symptoms with significant decrease of the dysphagia questionnaire (3). in group II all patients achieved a complete remissionof symptoms with significant decrease of the dysphagia questionnaire score (4,5) but 3 of them repeated the procedure. In boths groups the efficacy of the dilation was radiologically confirmed. Neither early nor late complications were reported in either groups. In our experience PD was an effective and safe procedure both in young and old patients although the older group had more recurrences, all successfully re-dilated

Long-distance quantum communication with atomic ensembles and linear optics

Quantum communication holds a promise for absolutely secure transmission of secret messages and faithful transfer of unknown quantum states. Photonic channels appear to be very attractive for physical implementation of quantum communication. However, due to losses and decoherence in the channel, the communication fidelity decreases exponentially with the channel length. We describe a scheme that allows to implement robust quantum communication over long lossy channels. The scheme involves laser manipulation of atomic ensembles, beam splitters, and single-photon detectors with moderate efficiencies, and therefore well fits the status of the current experimental technology. We show that the communication efficiency scale polynomially with the channel length thereby facilitating scalability to very long distances.Comment: 2 tex files (Main text + Supplement), 4 figure

Implementing mentor mothers in family practice to support abused mothers: Study protocol

Contains fulltext : 97988.pdf (postprint version ) (Open Access)ABSTRACT: BACKGROUND: Intimate partner violence is highly prevalent and mostly affects women with negative consequences for their physical and mental health. Children often witness the violence which has negative consequences for their well-being too. Care offered by family physicians is often rejected because abused women experience a too high threshold. Mentor mother support, a low threshold intervention for abused mothers in family practice, proved to be feasible and effective in Rotterdam, the Netherlands. The primary aim of this study is to investigate which factors facilitate or hinder the implementation of mentor mother support in family practice. Besides we evaluate the effect of mentor mother support in a different region. METHODS/DESIGN: An observational study with pre- and posttests will be performed. Mothers with home living children or pregnant women who are victims of intimate partner violence will be offered mentor mother support by the participating family physicians. The implementation process evaluation consists of focus groups, interviews and questionnaires. In the effect evaluation intimate partner violence, the general health of the abused mother, the mother-child relationship, social support, and acceptance of professional help will be measured twice (t = 0 and t = 6 months) by questionnaires, reporting forms, medical records and interviews with the abused mothers. Qualitative coding will be used to analyze the data from the reporting forms, medical records, focus groups, interviews, and questionnaires. Quantitative data will be analyzed with descriptive statistics, chi square test and t-test matched pairs. DISCUSSION: While other intervention studies only evaluate the feasibility and effectiveness of the intervention, our primary aim is to evaluate the implementation process and thereby investigate which factors facilitate or hinder implementation of mentor mother support in family practice.6 p

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. <p/>Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. <p/>Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

Biopsy confirmation of metastatic sites in breast cancer patients:clinical impact and future perspectives

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome,and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations,the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future,advances in targeted therapy will depend on the availability of metastatic tissue