Strain effect on electronic transport and ferromagnetic transition temperature in La0.9_{0.9}Sr0.1_{0.1}MnO3_{3} thin films

We report on a systematic study of strain effects on the transport properties and the ferromagnetic transition temperature $T_{c}$ of high-quality La$_{0.9}$Sr$_{0.1}$MnO$_{3}$ thin films epitaxially grown on (100) SrTiO$_{3}$ substrates. Both the magnetization and the resistivity are critically dependent on the film thickness. $T_{c}$ is enhanced with decreasing the film thickness due to the compressive stain produced by lattice mismatch. The resistivity above 165 K of the films with various thicknesses is consistent with small polaronic hopping conductivity. The polaronic formation energy $E_{P}$ is reduced with the decrease of film thickness. We found that the strain dependence of $T_{c}$ mainly results from the strain-induced electron-phonon coupling. The strain effect on $E_{P}$ is in good agreement with the theoretical predictions.Comment: 6 pages and 5 figures, accepted for publication in Phys. Rev.

Regular spectra in the vibron model with random interactions

The phenomenom of emerging regular spectral features from random interactions is addressed in the context of the vibron model. A mean-field analysis links different regions of the parameter space with definite geometric shapes. The results that are, to a large extent, obtained in closed analytic form, provide a clear and transparent interpretation of the high degree of order that has been observed in numerical studies.Comment: 19 pages, 8 figures, 2 tables. Physical Review C, in pres

The ER stress inducer DMC enhances TRAIL-induced apoptosis in glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour in humans and is highly resistant to current treatment modalities. We have explored the combined treatment of the endoplasmic reticulum (ER) stress-inducing agent 2,5-dimethyl-celecoxib (DMC) and TNF-related apoptosis-inducing ligand (TRAIL WT) or the DR5-specific TRAIL D269H/E195R variant as a potential new strategy to eradicate GBM cells using TRAIL-resistant and -sensitive GBM cells. GBM cell lines were investigated for their sensitivity to TRAIL, DMC and combination of both agents. Cell viability was measured by MTS assay and apoptosis was assessed by Annexin V/PI and acridine orange staining. Caspase activation and protein expression levels were analysed with Western blotting. Death Receptor (DR) cell surface expression levels were quantified by flow cytometry. DR5 expression was increased in U87 cells by ectopic expression using a retroviral plasmid and survivin expression was silenced using specific siRNAs. We demonstrate that A172 expresses mainly DR5 on the cell surface and that these cells show increased sensitivity for the DR5-specific rhTRAIL D269H/E195R variant. In contrast, U87 cells show low DR cell surface levels and is insensitive via both DR4 and DR5. We determined that DMC treatment displays a dose-dependent reduction in cell viability against a number of GBM cells, associated with ER stress induction, as shown by the up-regulation of glucose-regulated protein 78 (GRP78) and CCAAT/-enhancer-binding protein homologous protein (CHOP) in A172 and U87 cells. The dramatic decrease in cell viability is not accompanied by a correspondent increase in Annexin V/PI or caspase activation typically seen in apoptotic or/and necrotic cells within 24h of treatment. Although DMC did not affect DR5 expression in the GBM cells, it increased TRAIL-induced caspase-8 activation in both TRAIL-sensitive and -resistant cells, indicating that DMC potentiates initiator caspase activation in these cells. In A172 cells, sub-toxic concentrations of DMC greatly potentiated TRAIL-induced apoptosis. Furthermore, DMC strongly reduced survivin expression in A172 and U87 cells and silencing of this anti-apoptotic protein partially sensitized cells to TRAIL-induced apoptosis. Our findings corroborate that DMC is a promising agent against GBM, and uncovers a potential synergistic cooperation with TRAIL in this highly malignant cancer

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Differences in avoidable mortality between migrants and the native Dutch in the Netherlands

BACKGROUND: The quality of the healthcare system and its role in influencing mortality of migrant groups can be explored by examining ethnic variations in 'avoidable' mortality. This study investigates the association between the level of mortality from 'avoidable' causes and ethnic origin in the Netherlands and identifies social factors that contribute to this association. METHODS: Data were obtained from cause of death and population registries in the period 1995–2000. We compared mortality rates for selected 'avoidable' conditions for Turkish, Moroccan, Surinamese and Antillean/Aruban groups to native Dutch. RESULTS: We found slightly elevated risk in total 'avoidable' mortality for migrant populations (RR = 1.13). Higher risks of death among migrants were observed from almost all infectious diseases (most RR > 3.00) and several chronic conditions including asthma, diabetes and cerebro-vascular disorders (most RR > 1.70). Migrant women experienced a higher risk of death from maternity-related conditions (RR = 3.37). Surinamese and Antillean/Aruban population had a higher mortality risk (RR = 1.65 and 1.31 respectively), while Turkish and Moroccans experienced a lower risk of death (RR = 0.93 and 0.77 respectively) from all 'avoidable' conditions compared to native Dutch. Control for demographic and socioeconomic factors explained a substantial part of ethnic differences in 'avoidable' mortality. CONCLUSION: Compared to the native Dutch population, total 'avoidable' mortality was slightly elevated for all migrants combined. Mortality risks varied greatly by cause of death and ethnic origin. The substantial differences in mortality for a few 'avoidable' conditions suggest opportunities for quality improvement within specific areas of the healthcare system targeted to disadvantaged groups

Assessing the performance of maternity care in Europe: A critical exploration of tools and indicators

Background: This paper critically reviews published tools and indicators currently used to measure maternity care performance within Europe, focusing particularly on whether and how current approaches enable systematic appraisal of processes of minimal (or non-) intervention in support of physiological or "normal birth". The work formed part of COST Actions IS0907: "Childbirth Cultures, Concerns, and Consequences: Creating a dynamic EU framework for optimal maternity care" (2011-2014) and IS1405: Building Intrapartum Research Through Health - an interdisciplinary whole system approach to understanding and contextualising physiological labour and birth (BIRTH) (2014-). The Actions included the sharing of country experiences with the aim of promoting salutogenic approaches to maternity care. Methods: A structured literature search was conducted of material published between 2005 and 2013, incorporating research databases, published documents in english in peer-reviewed international journals and indicator databases which measured aspects of health care at a national and pan-national level. Given its emergence from two COST Actions the work, inevitably, focused on Europe, but findings may be relevant to other countries and regions. Results: A total of 388 indicators were identified, as well as seven tools specifically designed for capturing aspects of maternity care. Intrapartum care was the most frequently measured feature, through the application of process and outcome indicators. Postnatal and neonatal care of mother and baby were the least appraised areas. An over-riding focus on the quantification of technical intervention and adverse or undesirable outcomes was identified. Vaginal birth (no instruments) was occasionally cited as an indicator; besides this measurement few of the 388 indicators were found to be assessing non-intervention or "good" or positive outcomes more generally. Conclusions: The tools and indicators identified largely enable measurement of technical interventions and undesirable health (or pathological medical) outcomes. A physiological birth generally necessitates few, or no, interventions, yet most of the indicators presently applied fail to capture (a) this phenomenon, and (b) the relationship between different forms and processes of care, mode of birth and good or positive outcomes. A need was identified for indicators which capture non-intervention, reflecting the reality that most births are low-risk, requiring few, if any, technical medical procedures

Individual accumulation of heterogeneous risks explains perinatal inequalities within deprived neighbourhoods

Dutch' figures on perinatal mortality and morbidity are poor compared to EU-standards. Considerable within-country differences have been reported too, with decreased perinatal health in deprived urban areas. We investigated associations between perinatal risk factors and adverse perinatal outcomes in 7,359 pregnant women participating in population-based prospective cohort study, to establish the independent role, if any, for living within a deprived urban neighbourhood. Main outcome measures included perinatal death, intrauterine growth restriction (IUGR), prematurity, congenital malformations, Apgar at 5 min < 7, and pre-eclampsia. Information regarding individual risk factors was obtained from questionnaires, physical examinations, ultrasounds, biological samples, and medical records. The dichotomous Dutch deprivation indicator was additionally used to test for unexplained deprived urban area effects. Pregnancies from a deprived neighbourhood had an increased risk for perinatal death (RR 1.8, 95% CI [1.1; 3.1]). IUGR, prematurity, Apgar at 5 min < 7, and pre-eclampsia also showed higher prevalences (P < 0.05). Residing within a deprived neighbourhood was associated with increased prevalence of all measured risk factors. Regression analysis showed that the observed neighbourhood related differences in perinatal outcomes could be attributed to the increased risk factor prevalence only, without a separated role for living within a deprived neighbourhood. Women from a deprived neighbourhood had significantly more 'possibly avoidable' risk factors. To conclude, women from a socioeconomically deprived neighbourhood are at an increased risk for adverse pregnancy outcomes. Differences regarding possibly avoidable risk factors imply that preventive strategies may prove effective

An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2−/− γc−/− mouse

The occurrence of metastases is a critical determinant of the prognosis for breast cancer patients. Effective treatment of breast cancer metastases is hampered by a poor understanding of the mechanisms involved in the formation of these secondary tumor deposits. To study the processes of metastasis, valid in vivo tumor metastasis models are required. Here, we show that increased expression of the EGF receptor in the MTLn3 rat mammary tumor cell-line is essential for efficient lung metastasis formation in the Rag mouse model. EGFR expression resulted in delayed orthotopic tumor growth but at the same time strongly enhanced intravasation and lung metastasis. Previously, we demonstrated the critical role of NK cells in a lung metastasis model using MTLn3 cells in syngenic F344 rats. However, this model is incompatible with human EGFR. Using the highly metastatic EGFR-overexpressing MTLn3 cell-line, we report that only Rag2−/−γc−/− mice, which lack NK cells, allow efficient lung metastasis from primary tumors in the mammary gland. In contrast, in nude and SCID mice, the remaining innate immune cells reduce MTLn3 lung metastasis formation. Furthermore, we confirm this finding with the orthotopic transplantation of the 4T1 mouse mammary tumor cell-line. Thus, we have established an improved in vivo model using a Rag2−/− γc−/− mouse strain together with MTLn3 cells that have increased levels of the EGF receptor, which enables us to study EGFR-dependent tumor cell autonomous mechanisms underlying lung metastasis formation. This improved model can be used for drug target validation and development of new therapeutic strategies against breast cancer metastasis formation

Communication about genetic testing with breast and ovarian cancer patients: a scoping review

© 2018, The Author(s). Genetic testing of patients with cancer is increasingly offered to guide management, resulting in a growing need for oncology health professionals to communicate genetics information and facilitate informed decision-making in a short time frame. This scoping review aimed to map and synthesise what is known about health professionals’ communication about genetic testing for hereditary breast and ovarian cancer with cancer patients. Four databases were systematically searched using a recognised scoping review method. Areas and types of research were mapped and a narrative synthesis of the findings was undertaken. Twenty-nine papers from 25 studies were included. Studies were identified about (i) information needs, (ii) process and content of genetic counselling, (iii) cognitive and emotional impact, including risk perception and recall, understanding and interpretation of genetic test results, and anxiety and distress, (iv) patients’ experiences, (v) communication shortly after diagnosis and (vi) alternatives to face-to-face genetic counselling. Patients’ need for cancer-focused, personalised information is not always met by genetic counselling. Genetic counselling tends to focus on biomedical information at the expense of psychological support. For most patients, knowledge is increased and anxiety is not raised by pre-test communication. However, some patients experience anxiety and distress when results are disclosed, particularly those tested shortly after diagnosis who are unprepared or unsupported. For many patients, pre-test communication by methods other than face-to-face genetic counselling is acceptable. Research is needed to identify patients who may benefit from genetic counselling and support and to investigate communication about hereditary breast and ovarian cancer by oncology health professionals