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Micro-computed X-ray tomography (μCT) is a volumetric imaging tool used to quantify the internal structure of materials. μCT imaging with mechanical testing (in situ μCT) helps visualize strain-induced structural changes and develop structure-property relationships. However, the effects on thermophysical properties of radiation exposure during in situ μCT imaging are seldom addressed, despite potential radiation sensitivity in elastomers. This work quantifies the radiation dosage effect on thermo-, chemical-, and mechanical-properties for a vinyl nitrile-based foam. Material properties were measured after (0, 1, 2, and 3)days at (8.1±0.9)kGy/d. Morphological characteristics were investigated via scanning electron microscopy. Thermal transitions were assessed using differential scanning calorimetry. Viscoelasticity was measured with dynamic mechanical analysis over a range from -30°C to 60°C. Higher dose lead to stiffening and increased dissipation. Chemical structure was assessed with Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy. Soxhlet extraction was used to measure gel content. In summary, substantial changes occur in thermophysical properties, which may confound structure-property measurements. However, this also provides a modification pathway. Quantitation and calibration of the properties changes informed a finite element user material for material designers to explore tunablity and design optimization for impact protection engineers.

To equip graduates to respond to sustainability challenges, higher education institutions are developing programs and innovative pedagogical approaches that target new types of 21st century knowledge and skills. Resilience is a core concept in sustainability discourse, and one that is also driving pedagogical innovation that targets specific learner attributes. We argue that the topic of community resilience – as a theoretical boundary object – presents rich opportunities for transdisciplinary Education for Sustainable Development (ESD). This paper highlights international and cross-disciplinary trends in learning design for community resilience-focused university programs. The results outline the survey responses of 111 educators, researchers, and practitioners from a range of disciplines. One-way analysis of variance showed consistent results across the different groups of participants, regardless of geographic location, disciplinary background, or employment context. The research offers a learning design framework for teaching community resilience in higher education institutions, highlighting the importance of academic—practitioner collaboration in program development, disciplinary expertise to inform transdisciplinary learning, hybridised pedagogical approaches, and fostering student agency through assessment tasks.

Objective: To evaluate if an internet-delivered parent training program is noninferior to its group-delivered counterpart in reducing child disruptive behavior problems (DBP)., Method: This noninferiority randomized clinical trial enrolled families seeking treatment in primary care in Stockholm, Sweden, for DBP in a child 3-11 years of age. Participants were randomized to internet-delivered (iComet) or group-delivered (gComet) parent training. The primary outcome was parent-rated DBP. Assessments were made at baseline and 3, 6, and 12 months. Secondary outcomes included child and parent behaviors and well-being and treatment satisfaction. The noninferiority analysis was determined by a one-sided 95% CI of the mean difference between gComet and iComet using multilevel modeling., Results: This trial included 161 children (mean age 8.0); 102 (63%) were boys. In both intention-to-treat and per-protocol analyses, iComet was noninferior to gComet. There were small differences in between-group effect sizes (d = -0.02 to 0.13) on the primary outcome with the upper limit of the one-sided 95% CI below the noninferiority margin at 3-, 6-, and 12-month follow-up. Parents were more satisfied with gComet (d = 0.49, 95% CI [0.26, 0.71]). At 3-month follow-up, there were also significant differences in treatment effect on attention-deficit/hyperactivity disorder symptoms (d = 0.34, 95% CI [0.07, 0.61]) and parenting behavior (d = 0.41, 95% CI [0.17, 0.65]) favoring gComet. At 12-month follow-up, there were no differences in any outcomes., Conclusion: Internet-delivered parent training was noninferior to group-delivered parent training in reducing child DBP. The results were maintained at 12-month follow-up. This study supports internet-delivered parent training being used as an alternative to group-delivered parent training in clinical settings., Clinical Trial Registration Information: Randomized Controlled Trial of Comet via the Internet or in Group Format; https://www., Clinicaltrials: gov/; NCT03465384., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Adverse childhood experiences (ACE), including maltreatment and household dysfunction, are consistent predictors of health compromising behaviors in adulthood. While most ACE studies have focused on adults, there is an emerging body of research focusing on young adulthood., Methods: This review describes research focused on the relationship between ACE and substance use among young adults. Two databases were searched for studies published from 1998 to 2021 that assess the relationship between ACE and substance use among young adults. Of the 1474 articles identified in the search, 43 met the inclusion criteria., Results: Consensus across reviewed studies is that the relationship between ACE and substance use demonstrated in the general adult population is evident in young adults, although effects varied by demographic variables such as gender and ethnic background., Conclusions: The need for standardized measures across studies, racial/ethnic considerations, and the importance of building trauma informed prevention programs targeting this age group are discussed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Perceived discrimination, perceptions of receiving differential treatment due to negative attitudes, and stereotypes about one's racial/ethnic group can increase vulnerability to depression and anxiety. Although ethnic minority youth now represent over half of the U.S. youth population, few studies have investigated potential protective factors in the relationship between perceived discrimination and mental health across diverse ethnic minority immigrant youth from different cultural backgrounds., Methods: We examined the association between perceived discrimination and past week symptoms of depression and anxiety and whether patterns of problem and emotion-focused coping moderate these relationships among Somali and Hispanic immigrant youth (N = 353) in an urban midwestern setting (mean age = 15; 53% male, 39% first generation, 75% low income). Path analysis models examined the main effects of perceived discrimination for depression and anxiety and whether problem and emotion-focused coping moderated these associations., Results: Path analysis models suggest that perceived discrimination was positively associated with past week symptoms of depression (β = .37, standard error = .06) and anxiety (β = .16, standard error = .06) across ethnicity. However, adolescents who reported high levels of discrimination and who used predominantly problem-focused coping strategies experienced fewer internalizing problems than youth who relied predominantly on emotion-focused coping strategies., Conclusions: Our findings suggest that strengthening youths' problem-focused coping strategies in the face of discriminatory stress is a promising health promotion and risk prevention approach., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The side effects of systemic cancer therapy and the lack of clinical data on safety and efficacy of COVID-19 vaccination in cancer patients cause uncertainty among the patients about whether to get vaccinated or not. Here, we evaluated attitude towards and effects of COVID-19 vaccination in patients with breast and gynecological cancer undergoing systemic cancer therapy., Methods: Since March 15th, 2021, cancer patients who received one of the approved COVID-19 vaccines were routinely interviewed about immediate and late side effects. Clinical parameters such as current therapy, time interval between therapy administration and vaccination, and changes in the therapy schedule due to vaccination were documented. The collected data were analyzed de-identified as a part of routine quality assurance., Results: By July 27th, 2021, 218 patients (74.3% breast cancer patients) had received one of two COVID-19 vaccine doses, and 112 patients had received both doses: 77.5% received Conmirnaty (BioNTech/Pfizer), 16.1% Vaxzevria (Astra Zeneca) and 5.9% COVID-19 Vaccine Moderna. The COVID-19 vaccines had an acceptable safety profile with self-limiting local and systemic adverse events, which rarely lasted >48 h post vaccination. Symptoms occurred predominantly after the second dose of the vaccine and less frequently in older patients >55 years. No vaccine-related serious adverse events were reported, and only limited effects of vaccination on the therapy schedule were observed., Conclusions: Breast and gynecologic cancer patients tolerate the COVID-19 vaccination while undergoing systemic cancer therapy without any additional side effects beyond those reported in the general population., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study assessed the checkpoint kinase 1 inhibitor prexasertib in patients with extensive-stage small-cell lung cancer (ED-SCLC)., Patients and Methods: This was a parallel-cohort phase II study of 105 mg/m 2 prexasertib once every 14 days for patients who progressed after no more than two prior therapies and had platinum-sensitive (Cohort 1) or platinum-resistant/platinum-refractory (Cohort 2) disease. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Exploratory endpoints included biomarker identification and assessment of an alternative regimen (Cohort 3: 40 mg/m 2 days 1-3, 14-day cycle)., Results: In Cohort 1 (n = 58), ORR was 5.2%; DCR, 31%; median PFS, 1.41 months (95% confidence interval [CI], 1.31-1.64); and median OS, 5.42 months (95% CI, 3.75-8.51). In Cohort 2 (n = 60), ORR was 0%; DCR, 20%; median PFS, 1.36 months (95% CI, 1.25-1.45); and median OS, 3.15 months (95% CI, 2.27-5.52). The most frequent all-grade, related, treatment-emergent adverse events were decreased neutrophil count (Cohort 1, 69.6%; Cohort 2, 73.3%), decreased platelet count (Cohort 1, 51.8%; Cohort 2, 50.0%), decreased white blood cell count (Cohort 1, 28.6%; Cohort 2, 40.0%), and anemia (Cohort 1, 39.3%; Cohort 2, 28.3%). Eleven patients (19.6%) in Cohort 1 and one patient (1.7%) in Cohort 2 experienced grade ≥3 febrile neutropenia. Prexasertib pharmacokinetics were consistent with prior studies. Cohort 3 outcomes were similar to those of Cohorts 1 and 2. No actionable biomarkers were identified., Conclusion: Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The increasing frequency and complexity of cancer genomic profiling represents a challenge for the oncology community. Results from next-generation sequencing-based clinical tests require expert review to determine their clinical relevance and to ensure patients are stratified appropriately to established therapies or clinical trials., Methods: The Sarah Cannon Research Institute UK/UCL Genomics Review Board (GRB) was established in 2014 and represents a multidisciplinary team with expertise in molecular oncology, clinical trials, clinical cancer genetics and molecular pathology. Prospective data from this board were collated., Results: To date, 895 patients have been reviewed by the GRB, of whom 180 (20%) were referred for clinical trial screening and 62 (7%) received trial therapy. For a further 106, a clinical trial recommendation was given., Conclusions: Numerous challenges are faced in implementing a GRB, including the identification of potential germline variants, the interpretation of variants of uncertain significance and consideration of the technical limitations of pathology material when interpreting results. These challenges are likely to be encountered with increasing frequency in routine practice. This GRB experience provides a model for the multidisciplinary review of molecular profiling data and for the linking of molecular analysis to clinical trial networks., Competing Interests: Competing interests: PB has participated in ThermoFisher’s European Clinical Oncology Advisory Board meetings, and has delivered sponsored, but not for profit, presentations at the invitation of ThermoFisher UK on a number of occasions. CS reports grant support from Cancer Research UK, UCLH Biomedical Research Council, Rosetrees Trust and AstraZeneca. Personal fees from Boehringer Ingelheim, Novartis, Eli Lilly, Roche Ventana, GlaxoSmithKline, Pfizer, Genentech and Celgene. Stock options in GRAIL, APOGEN Biotechnologies and EPIC Bioscience and has stock options and is cofounder of Achilles Therapeutics.

Background: Gastrointestinal (GI) cancer patients may not be considered for therapy with fluoropyrimidines (FPs) because of previous cardiovascular (CV) toxicity or preexisting risk factors; such patients may benefit from raltitrexed-based therapy., Patients and Methods: Patient, tumor, and treatment characteristics, as well as clinical outcomes of all consecutively treated patients with raltitrexed at the Royal Marsden Hospital between October 1998 and July 2011 were examined. GI cancer patients who developed CV toxicity as a result of FPs and those with significant CV risk factors receiving raltitrexed were included in this analysis., Results: A total of 247 patients (155 and 92 with CV FP-related CV toxicities and significant CV risk factors, respectively) treated with raltitrexed alone or in combination were examined after a median follow-up of 47.1 months. CV toxicity profiles of patients receiving capecitabine (n = 110) and 5-fluorouracil (n = 45) were largely similar. Of raltitrexed-treated patients, 13 (5%) experienced CV toxicities and 1 (< 0.1%) died as a result of myocardial infarction. The median progression-free survival (PFS) and overall survival (OS) were 36.0 months (95% confidence interval [CI], 26.5-48.6) and 44.3 months (95% CI, 33.1-56.8), respectively. The 5-year survival for early stage GI malignancies (n = 140) was 62.0% (95% CI, 50.1-71.9). Median PFS and OS were not reached in this group (interquartile range = 38.4 months to NR); median PFS and OS for advanced GI malignancies (n = 107) were 18.8 (95% CI, 11.9-25.7) and 23.7 months (95% CI, 17.0-26.9), respectively., Conclusion: A raltitrexed-based regimen is well-tolerated therapy with comparable efficacy to FPs in patients with GI malignancies with significant CV toxicities or risk factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Poor family management and antisocial peer associations are related risk factors for negative outcomes such as adolescent substance misuse and conduct disorders. The relationship between family management and antisocial peer associations is complex. The purpose of this study was to test the reciprocal relationships between youth-reports of poor family management and antisocial peer associations over multiple time-points., Methods: We used four data points (5th-11th grade) from the Australian arm of the longitudinal International Youth Development Study (IYDS) to test a random-intercepts cross-lagged path model (N = 922)., Results: The model fit the data well with path estimates showing that poor family management predicted greater antisocial peer associations at the next wave but not the reverse. A second model included a third autoregressive path to control for youth's own antisocial behavior; the direction of the relationships between poor family management and antisocial peer associations did not change., Conclusions: These results indicate that across adolescence poor family management predicts greater antisocial peer association, which provides evidence that family-focused interventions are an important prevention strategy even in adolescence., (Copyright © 2018 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Objectives: p16 INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven., Materials and Methods: We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression., Results: While p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (-) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (-) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (-)/p16-high tumors., Conclusions: RPPA data suggest high p16 protein expression in many HPV (-) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The predominant framing of indigenous people's alcohol use as problematic has resulted in narrow understandings of indigenous alcohol use in general. In particular, there has been little exploration of how Māori, those indigenous to Aotearoa/New Zealand, contextualise and understand their alcohol use. To build on current understandings of Māori alcohol use, this study explored the broader and socially shared meanings of alcohol use from the perspectives of older Māori., Methods: Hui (meeting/s) were held with five kaupapa whānau (groups with a common purpose) comprising older Māori (n = 19) who shared their perspectives on Māori alcohol use. Data were analysed using a master/counter discursive narrative analytical framework., Results: The results show that older Māori drew on a number of discursive strategies to construct three cultural narratives of Māori alcohol use. These were: 'Not all Māori are problem drinkers', 'There is good Māori alcohol use', and 'Alcohol is not the problem'. These narratives simultaneously supported and challenged the dominant narrative that problematises Māori alcohol use., Conclusion: These findings can be used to inform future research to show Māori understandings of alcohol use. Such research will support the development of culturally responsive alcohol policy and health promotion initiatives aimed at addressing alcohol related issues among Māori and thereby improve Māori health and wellbeing., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The tobacco heating product THP1.0, which heats but does not burn tobacco, was tested as part of a modified-risk tobacco product assessment framework for its impacts on indoor air quality and residual tobacco smoke odour. THP1.0 heats the tobacco to less than 240 °C ± 5 °C during puffs. An environmentally controlled room was used to simulate ventilation conditions corresponding to residential, office and hospitality environments. An analysis of known tobacco smoke constituents, included CO, CO 2 , NO, NO 2 , nicotine, glycerol, 3-ethenyl pyridine, sixteen polycyclic aromatic hydrocarbons, eight volatile organic compounds, four carbonyls, four tobacco-specific nitrosamines and total aerosol particulate matter. Significant emissions reductions in comparison to conventional cigarettes were measured for THP1.0. Levels of nicotine, acetaldehyde, formaldehyde and particulate matter emitted from THP1.0 exceeded ambient air measurements, but were more than 90% reduced relative to cigarette smoke emissions within the laboratory conditions defined Residual tobacco smoke odour was assessed by trained sensory panels after exposure of cloth, hair and skin to both mainstream and environmental emissions from the test products. Residual tobacco smoke odour was significantly lower from THP1.0 than from a conventional cigarette. These data show that using THP1.0 has the potential to result in considerably reduced environmental emissions that affect indoor air quality relative to conventional cigarettes., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

A novel tobacco heating product, THP1.0, that heats tobacco below 245 °C is described. It was designed to eliminate tobacco combustion, while heating tobacco to release nicotine, tobacco volatiles and glycerol to form its aerosol. The stewardship assessment approach behind the THP 1.0 design was based on established toxicological principles. Thermophysical studies were conducted to examine the extent of tobacco thermal conversion during operation. Thermogravimetric analysis of the tobacco material revealed the major thermal behaviour in air and nitrogen up to 900 °C. This, combined with the heating temperature profiling of the heater and tobacco rod, verified that the tobacco was not subject to combustion. The levels of tobacco combustion markers (CO, CO 2 , NO and NO x ) in the aerosol of THP1.0 were significantly lower than the levels if there were any significant pyrolysis or combustion. Quantification of other tobacco thermal decomposition and evaporative transfer markers showed that these levels were, on average, reduced by more than 90% in THP1.0 aerosol as compared with cigarette smoke. The physical integrity of the tobacco consumable rod showed no ashing. Taken together, these data establish that the aerosol generated by THP1.0 is produced mainly by evaporation and distillation, and not by combustion or pyrolysis., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

For a tobacco heating product (THP), which heats rather than burns tobacco, the emissions of toxicants in the aerosol were compared with those in cigarette smoke under a machine-puffing regimen of puff volume 55 ml, puff duration 2 s and puff interval 30 s. The list of toxicants included those proposed by Health Canada, the World Health Organization Study Group on Tobacco Product Regulation (TobReg), the US Food and Drug Administration and possible thermal breakdown products. In comparison to the University of Kentucky 3R4F reference cigarette the toxicant levels in the THP1.0 emissions were significantly reduced across all chemical classes. For the nine toxicants proposed by TobReg for mandated reduction in cigarette emissions, the mean reductions in THP1.0 aerosol were 90.6-99.9% per consumable with an overall average reduction of 97.1%. For the abbreviated list of harmful and potentially harmful constituents of smoke specified by the US Food and Drug Administration Tobacco Products Scientific Advisory Committee for reporting in cigarette smoke (excluding nicotine), reductions in the aerosol of THP1.0 were 84.6-99.9% per consumable with an overall average reduction of 97.5%., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Lurbinectedin (PM01183) has synergistic antitumor activity when combined with doxorubicin in mice with xenografted tumors. This phase I trial determined the recommended dose (RD) of doxorubicin (bolus) and PM01183 (1-h intravenous infusion) on day 1 every 3 weeks (q3wk), and obtained preliminary evidence of antitumor activity for this combination in small-cell lung cancer (SCLC)., Patients and Methods: Patients with advanced solid tumors received doxorubicin and PM01183 following a standard dose escalation design and expansion at the RD. Twenty-seven patients had relapsed SCLC: 12 with sensitive disease (platinum-free interval ≥90 days) and 15 with resistant disease (platinum-free interval <90 days)., Results: Doxorubicin 50 mg/m2 and PM01183 4.0 mg flat dose was the RD. In relapsed SCLC, treatment tolerance at the RD was manageable. Transient and reversible myelosuppression (including neutropenia, thrombocytopenia, and febrile neutropenia) was the main toxicity, managed with dose adjustment and colony-stimulating factors. Fatigue (79%), nausea/vomiting (58%), decreased appetite (53%), mucositis (53%), alopecia (42%), diarrhea/constipation (42%), and asymptomatic creatinine (68%) and transaminase increases (alanine aminotransferase 42%; aspartate aminotransferase 32%) were common, and mostly mild or moderate. Complete (n = 2, 8%) and partial response (n = 13, 50%) occurred in relapsed SCLC, mostly at the RD. Response rates at second line were 91.7% in sensitive disease [median progression-free survival (PFS)=5.8 months] and 33.3% in resistant disease (median PFS = 3.5 months). At third line, response rate was 20.0% (median PFS = 1.2 months), all in resistant disease., Conclusion: Doxorubicin 50 mg/m2 and PM01183 4.0 mg flat dose on day 1 q3wk has shown remarkable activity, mainly in second line, with manageable tolerance in relapsed SCLC, leading to further evaluation of this combination within an ongoing phase III trial., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Context: Spiritual, existential, and psychological issues represent central components of quality of life (QOL) in palliative care. A better understanding of the dynamic nature underlying these components is essential for the development of interventions tailored to the palliative context., Objectives: The aims were to explore 1) the relationship between spirituality, meaning in life, wishes for hastened death and psychological distress in palliative patients and 2) the extent to which these nonphysical determinants influence QOL., Methods: A cross-sectional study involving face-to-face interviews with Swiss palliative patients was performed, including the Schedule for Meaning in Life Evaluation (SMILE), the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), the Idler Index of Religiosity (IIR), the Hospital Anxiety and Depression Scale (HADS), and the Schedule of Attitudes toward Hastened Death (SAHD). QOL was measured with a single-item visual analogue scale (0-10)., Results: Two hundred and six patients completed the protocol (51.5% female; mean age = 67.5 years). The results indicated a significant negative relationship between FACIT-Sp/SMILE and HADS total scores (P = 0.000). The best model for QOL explained 32.8% of the variance (P = 0.000) and included the FACIT-Sp, SMILE, and SAHD total scores, the IIR "private religiosity" score, as well as the HADS "depression" score., Conclusion: Both spiritual well-being and meaning in life appear to be potential protective factors against psychological distress at the end of life. Since nonphysical determinants play a major role in shaping QOL at the end of life, there is a need for the development of meaning-oriented and spiritual care interventions tailored to the fragility of palliative patients., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Ayurveda claims to be effective in the treatment of psychosomatic disorders by means of lifestyle and nutritional counseling., Design: In a randomized controlled study mothers with burnout were randomized into two groups: Ayurvedic nutritional counseling (according to tradition), and conventional nutritional counseling (following the recommendations of a family doctor). Patients received five counseling sessions over twelve weeks., Main Outcome Measures: Outcomes included levels of burnout, quality of life, sleep, stress, depression/anxiety, and spirituality at three and six months. It also included a qualitative evaluation of the communication processes., Results: We randomized thirty four patients; twenty three participants were included in the per protocol analysis. No significant differences were observed between the groups. However, significant and clinically relevant intra-group mean changes for the primary outcome burnout, and secondary outcomes sleep, stress, depression and mental health were only found in the Ayurveda group. The qualitative part of the study identified different conversational styles and counseling techniques between the two study groups. In conventional consultations questions tended to be category bound, while counseling-advice was predominantly admonitory. The Ayurvedic practitioner used open-ended interrogative forms, devices for displaying understanding, and positive re-evaluation more frequently, leading to an overall less asymmetrical interaction., Conclusions: We found positive effects for both groups, which however were more pronounced in the Ayurvedic group. The conversational and counseling techniques in the Ayurvedic group offered more opportunities for problem description by patients as well as patient-centered practice and resource-oriented recommendations by the physician., Trial Registration: NCT01797887., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This paper has a rather audacious purpose: to present a comprehensive theory explaining, and further providing hypotheses for the empirical study of, the multiple ways by which people respond to art. Despite common agreement that interaction with art can be based on a compelling, and occasionally profound, psychological experience, the nature of these interactions is still under debate. We propose a model, The Vienna Integrated Model of Art Perception (VIMAP), with the goal of resolving the multifarious processes that can occur when we perceive and interact with visual art. Specifically, we focus on the need to integrate bottom-up, artwork-derived processes, which have formed the bulk of previous theoretical and empirical assessments, with top-down mechanisms which can describe how individuals adapt or change within their processing experience, and thus how individuals may come to particularly moving, disturbing, transformative, as well as mundane, results. This is achieved by combining several recent lines of theoretical research into a new integrated approach built around three processing checks, which we argue can be used to systematically delineate the possible outcomes in art experience. We also connect our model's processing stages to specific hypotheses for emotional, evaluative, and physiological factors, and address main topics in psychological aesthetics including provocative reactions-chills, awe, thrills, sublime-and difference between "aesthetic" and "everyday" emotional response. Finally, we take the needed step of connecting stages to functional regions in the brain, as well as broader core networks that may coincide with the proposed cognitive checks, and which taken together can serve as a basis for future empirical and theoretical art research., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 41/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively., (Copyright © 2015. Published by Elsevier B.V.)

Objective: To conduct a systematic review of the literature examining risk and protective factors of alcohol related negative consequences (ARNCs) among adolescents., Methods: We conducted a systematic search of original empirical articles published between January 1, 1990 and June 1, 2015. The qualitative synthesis was performed using the Theory of Triadic Influence as a framework., Results: Fifty-two studies were reviewed. Intrapersonal (e.g., personality traits, drinking motives and expectancies, depression), interpersonal (e.g., parental and peer alcohol use, violence exposure) and attitudinal factors (e.g., media exposure to alcohol, religiosity) influence ARNCs. Emerging evidence of new trends contributing to ARNCs include ready mixed alcohol drinks and childhood trauma and abuse., Conclusions: Risk factors from all domains of influence were observed. More research is needed on protective factors and how alcohol use interacts with preventive factors in predicting ARNCs. The conceptualization of negative consequences varies significantly between studies and may impact the external validity of previous research., (Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Myofibrillar myopathies (MFM) are progressive diseases of human heart and skeletal muscle with a severe impact on life quality and expectancy of affected patients. Although recently several disease genes for myofibrillar myopathies could be identified, today most genetic causes and particularly the associated mechanisms and signaling events that lead from the mutation to the disease phenotype are still mostly unknown. To assess whether the zebrafish is a suitable model system to validate MFM candidate genes using targeted antisense-mediated knock-down strategies, we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally. Consistently, targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure. Similar to what was shown in MFM patients, MFM gene-deficient zebrafish showed pronounced gene-specific phenotypic and structural differences. In summary, our results indicate that the zebrafish is a suitable model to functionally and structurally evaluate novel MFM disease genes in vivo., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine the impact of quantity and location of aortic valve calcification (AVC) on paravalvular regurgitation (PVR) and rates of post-dilation (PD) immediately after transcatheter aortic valve replacement (TAVR)., Background: The impact of AVC in different locations within the aortic valve complex is incompletely understood., Methods: This study analyzed 150 patients with severe, symptomatic aortic stenosis who underwent TAVR. Total AVC volume scores were calculated from contrast-enhanced multidetector row computed tomography imaging. AVC was divided by leaflet sector and region (Leaflet, Annulus, left ventricular outflow tract [LVOT]), and a combination of LVOT and Annulus (AnnulusLVOT). Asymmetry was assessed. Receiver-operating characteristic analysis was performed with greater than or equal to mild PVR and PD as classification variables. Logistic regression was performed., Results: Quantity of and asymmetry of AVC for all regions of the aortic valve complex predicted greater than or equal to mild PVR by receiver-operating characteristic analysis (area under the curve = 0.635 to 0.689), except Leaflet asymmetry. Receiver-operating characteristic analysis for PD was significant for quantity and asymmetry of AVC in all regions, with higher area under the curve values than for PVR (area under the curve = 0.648 to 0.741). On multivariable analysis, Leaflet and AnnulusLVOT calcification were independent predictors of both PVR and PD regardless of multidetector row computed tomography area cover index., Conclusions: Quantity and asymmetry of AVC in all regions of the aortic valve complex predict greater than or equal to mild PVR and performance of PD, with the exception of Leaflet asymmetry. Quantity of AnnulusLVOT and Leaflet calcification independently predict PVR and PD when taking into account multidetector row computed tomography area cover index., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

This study examined the effectiveness of a Swedish parent management training (PMT) intervention for parents of children aged 3 to 10 within the context of regular social service. Self-referred parents of 159 children (aged 3 to 10) with conduct problems were randomly assigned to either 11 practitioner-assisted group sessions (PMT-P), or a single instructional workshop followed by self-administration of the training material (PMT-S), or a waitlist control group. Intent-to-treat analyses showed that both PMT-P and PMT-S improved parent competence and reduced child conduct problems compared to the waitlist at posttest. Both training conditions showed further significant improvements at the 6-month follow-up. In direct comparison, PMT-P was superior to PMT-S on measures of child conduct problems at both posttest and follow-up. Improvement in child conduct was mediated by improvement in parent competencies and homework fidelity. The findings in this study have implications for large-scale dissemination of parent management training through different means of delivery., (Copyright © 2010. Published by Elsevier Ltd.)

Background Aims: Current clinical trials utilize non-selected bone marrow (BM) mononuclear cells (MNC) to augment vasculo genesis within ischemic vascular beds. Recent reports have identified a diminished number and function of hemat-opoietic stem cells (HSC) from aged and diseased patients. Umbilical cord blood (UCB) provides a potential robust allo-geneic source of HSC for therapeutic vasculogenesis., Methods: MNC and magnetically isolated CD133(+) cells were assessed for viability (trypan blue) and surface phenotype (flow cytometry). To test in vivo functionality of the cells, NOD/SCID mice underwent ligation of the right femoral artery followed immediately by cell injection. Blood flow recovery, necrosis, BM engraftment of human cells and histologic capillary density were determined. Cells were tested for potential mechanisms mediating the in vivo effects, including migration, cytokine secretion and angiogenic augmentation (Matrigel assays)., Results: Surface expression analysis showed CD31 (PECAM) expression was greatly increased in UCB CD133(+) cells compared with BM MNC. At 28 days, perfusion ratios were highest in animals receiving UCB CD133(+) cells, while animals receiving BM CD133(+) cells and BM MNC demonstrated perfusion ratios statistically higher than in animals treated with cytokine media alone. Animals receiving CD133(+) cells showed a statistically higher capillary density, reduced severe digit necrosis and increased engraftment in the BM than animals treated with unselected BM MNC. In vitro studies showed equivalent migration to stromal-derived factor-1 (SDF-1), increased production of tumor necrosis factor alpha (TNF-alpha) and increased branch points with the co-incubation of CD133(+) cells with human umbilical vein endothelial cells (HUVEC) in the Matrigel angiogenesis assay., Conclusions: Taken together, UCB CD133(+) cells exhibit robust vasculogenic functionality compared with BM MNC in response to ischemia.

Acute myelogenous leukemia is driven by leukemic stem cells (LSCs) generated by mutations that confer (or maintain) self-renewal potential coupled to an aberrant differentiation program. Using retroviral mutagenesis, we identified genes that generate LSCs in collaboration with genetic disruption of the gene encoding interferon response factor 8 (Irf8), which induces a myeloproliferation in vivo. Among the targeted genes, we identified Mef2c, encoding a MCM1-agamous-deficiens-serum response factor transcription factor, and confirmed that overexpression induced a myelomonocytic leukemia in cooperation with Irf8 deficiency. Strikingly, several of the genes identified in our screen have been reported to be up-regulated in the mixed-lineage leukemia (MLL) subtype. High MEF2C expression levels were confirmed in acute myelogenous leukemia patient samples with MLL gene disruptions, prompting an investigation of the causal interplay. Using a conditional mouse strain, we demonstrated that Mef2c deficiency does not impair the establishment or maintenance of LSCs generated in vitro by MLL/ENL fusion proteins; however, its loss led to compromised homing and invasiveness of the tumor cells. Mef2c-dependent targets included several genes encoding matrix metalloproteinases and chemokine ligands and receptors, providing a mechanistic link to increased homing and motility. Thus, MEF2C up-regulation may be responsible for the aggressive nature of this leukemia subtype.

Many localised, superficial bladder cancers can be effectively controlled. However, disease which has spread to nodes outside the pelvis or to distant organs is generally incurable and systemic therapies, rather than surgery, are appropriate. Combination chemotherapy based around established cytotoxic drugs such as cisplatin has proven benefit in palliating symptoms and prolonging survival in responsive patients with advanced disease. Combination chemotherapies which include newer cytotoxic drugs such as gemcitabine provide the potential for equivalent efficacy with less toxicity than established regimens. Between the extremes of superficial and advanced disease, muscle-invasive bladder cancers have traditionally been treated, with curative intent, by radical surgery or radiotherapy. However, newly published data suggest, for the first time, genuine survival benefits from peri-operative chemotherapy. This article reviews the evidence for cisplatin-based chemotherapy in advanced disease, assesses the potential benefits of newer cytotoxic drugs, discusses the latest evidence pertaining to peri-operative chemotherapy in muscle-invasive disease, and looks forward to potential new biological agents in the systemic therapy of bladder cancer.