Cancer Treatment Survey (CaTS): development and validation of a new instrument to measure patients' preparation for chemotherapy and radiotherapy

Objective: Cancer patients experience high levels of pre-treatment anxiety. Chemotherapy and radiotherapy are threatening medical procedures. Preparation for these procedures should include the provision of sensory and procedural information, and addressing fears. The aim of this study was to develop a cancer treatment survey (CaTS) to assess the preparation for chemotherapy and radiotherapy in cancer patients.

Methods: Drawing on evidence for how to prepare patients for threatening procedures, items were generated by psychosocial/clinical experts and pilot tested with cancer patients. The 36-item draft CaTS was administered to 192 cancer patients commencing chemotherapy for lymphoma, breast or colon cancer. Participants also completed the Hospital Anxiety and Depression Scale (HADS) and basic medical and demographic information was recorded.

Results: A systematic process of item selection removed 11 items. Factor analysis indicated a two-factor solution, with 11 items representing sensory/psychological concerns and 14 items representing procedural concerns. The two subscales demonstrated excellent internal reliability with Cronbach's alpha both over 0.90 and the average inter-item correlation for each scale exceeded 0.30. Divergent validity was established for both CaTS subscales with the HADS-A and-T (all r<0.30). Younger participants (under 65 years of age) had significantly greater procedural concerns (p = 0.001; medium effect).

Conclusions: The CaTS is a two factor, 25-item measure that assesses sensory/psychological concerns and procedural concerns relating to cancer treatment. The instrument provides a reliable and valid outcome measure for interventions to prepare cancer patients for chemotherapy and radiotherapy.

Negotiating and creating intercultural relations: Chinese immigrant children in New Zealand early childhood education centres

A multiple-case study investigation of the experiences of eight Chinese immigrant children in New Zealand early childhood centres suggested that the immigrant children’s learning experiences in their first centre can be understood as a process of negotiating and creating intercultural relations. The children’s use of family cultural tools, such as the Chinese language, was a distinctive feature of their learning experiences, simultaneously revealing and extending their exploration of the intercultural practices and their establishment of a sense of belonging. In the presence of Chinese-speaking peers who acted as ‘bridges’ and ‘boundary objects’, the Chinese language was actively used by the immigrant children in English-speaking early childhood centres and, as a result, they created intercultural relations which: (i) bridged the two cultures; (ii) brought the cultures into convergence; (iii) enabled the children to claim group identity; and (iv) battled intercultural constraints. The absence of Chinese speakers, on the other hand, constrained possibilities for intercultural relations. The focus on intercultural relations in this study is expected to lead to educational initiatives to support the incorporation of diverse cultures in early childhood services.

A longitudinal evaluation of the resilient families randomized trial to prevent early adolescent depressive symptoms

This study aimed to evaluate whether an intervention prevented the development of depressive symptoms through the early years of secondary school (Grades 7 to 9 - mean ages 12.3 to 14.5 years) in Victoria, Australia. Twelve schools were randomized to a universal preventative intervention (including a student social relationship/emotional health curriculum, and parent/caregiver parenting education); 12 were randomized as control schools. Multivariate regression analyses used student self-report to predict depressive symptoms at 26-month follow-up (13-months after intervention completion) from baseline measures and intervention status (N = 2027). There was no overall intervention effect on depressive symptoms. However, intervention students with moderate symptoms whose parents attended parent education events had a significantly reduced risk of depressive symptoms at follow-up. Future evaluations of interventions of this type should investigate: therapeutic processes; methods to increase recruitment into effective parent education events; and the potential to target assistance to students with high depressive symptoms.

A delayed inheritance: The Medical Board of Victoria's 75-year wait to find doctors guilty of "infamous conduct in a professional respect"

The Medical Board of Victoria (Board) was created in 1844 to register “legally qualified medical practitioners”. It was not until 1933, however, that the Board attained the power to remove from its register a doctor who had engaged in “infamous conduct in a professional respect” (the power), even though the General Council of Medical Education and Registration of the United Kingdom on which the Board was modelled had been granted the power 75 years earlier. This article argues that the delay in the Board’s inheritance was attributable to successive Victorian Parliaments’ distrust of the Board and that this attitude was unwarranted, at least from early in the 20th century. The article maintains that the granting of the power to the Board was a crucial event in the history of the regulation of the Victorian medical profession. This is illustrated both by the difficulty encountered by the medical profession in dealing with doctors’ unethical conduct before 1933, and the Board’s concern to use its new authority responsibly and appropriately to protect the public and the profession in the three years after it attained the power.

Symptoms of depression and difficulty initiating sleep from early adolescence to early adulthood: a longitudinal study

STUDY OBJECTIVES: To assess the direction of the relationship and degree of shared associations between symptoms of depression and difficulty initiating sleep (DIS) from early adolescence to early adulthood. DESIGN: Cross-sectional and longitudinal assessment of the symptoms of depression-DIS association from early adolescence (age 13 y) to early adulthood (age 23 y). SETTING: Hordaland, Norway. PARTICIPANTS: There were 1,105 individuals (55% male) who took part in the Norwegian Longitudinal Health Behaviour Study (NLHB) and participated at least once across seven data collection waves during the years 1990-2000. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Characteristic data were obtained during the first assessment. Symptoms of depression and instances of DIS were assessed during each data collection wave. Symptoms of depression and DIS were associated in all data waves, and one-step cross-lagged bivariate correlations were significant and comparatively high for both factors. Structural equation modelling indicated that DIS and symptoms of depression at wave 1 remain relatively stable across waves (all P < 0.001), and a significant and consistent unidirectional cross-lagged effect was noted running from symptoms of depression to DIS from early adolescence to early adulthood. DIS is only marginally and inconsistently associated with the lagged symptoms of depression score across waves. CONCLUSIONS: These results suggest that symptoms of depression established in early adolescence are a moderate predictor of difficulty initiating sleep (DIS) in early adulthood, whereas the reverse association of DIS predicting depression was not convincingly supported. These findings are in contrast to previous findings that suggest sleep problems as a risk factor for the later development of depression.

An integrative approach to characterize Malagasy bats of the subfamily Vespertilioninae Gray, 1821, with the description of a new species of Hypsugo

© 2015 The Linnean Society of London. Although important advances have been made in recent years in the taxonomy of different families and subfamilies of Malagasy bats, those belonging to the Vespertilioninae remain partially unresolved. Herein using a mitochondrial marker (cytochrome b) as the point of departure for 76 specimens of Malagasy vespers and appropriate African taxa, we diagnose the six taxa of this subfamily on the island by overlaying different morphological and bioacoustic characters on the clade structure of sequenced animals. The species include: endemic Neoromicia matroka, which is sister to African N. capensis; endemics N. malagasyensis and N. robertsi, which form sister species; a member of the genus Hypsugo, which is sister to African H. anchietae and described herein as new to science; Pipistrellus hesperidus for which Madagascar animals are genetically close but distinct from African populations of the same species; and endemic P. raceyi, which shows segregation of eastern (mesic) and western (dry) populations and its sister species relationships are unresolved. While the external and craniodental measurements, as well as bioacoustic variables, allow only partial differentiation of these six species of Vespertilioninae, molecular characters provide definitive separation of the taxa, as do male bacular morphology.

Alex E. Davis, Graduate of the New York Trade School

Alexander Davis, Jr., a graduate of the Carpentry program of the New York Trade School in 1955 is shown working. Original caption reads, "Carpenter Contractor, Alex E. Davis Builder, Easton, Pa. Alexander Davis, Jr. - Carpentry 1955. The remodeling of old and building of new houses etc., offers many opportunities for success. Mr. Davis is shown hanging a new door on a building." Black and white photograph with caption glued to reverse.

Working on a Lathe in the Carpentry Department of the New York Trade School

A student or teacher at the New York Trade School is shown working on a lathe in the Carpentry Department. Black and white photograph credited to the New York City Works Progress Administration.

Market entry of an innovative technology : the example of a new app on the Brazilian tourism market

The Brazilian start-up Local Wander plans to enter the tourism sector with a mobile application aiming to enable a new form of travel research. A web-based survey has been sent out to the start-up’s target audience (n: 236) in order to gain further relevant information for the designing of Local Wander’s market entry strategy. By applying the diffusion of innovation theory, this thesis could detect five different adopter categories, originally described by Rogers (1962), among Local Wander’s target audience based on their adoption intention. The Early Market was observed to be significantly bigger than the theory predicted. Research revealed four characteristics to be of significant impact on the adoption intention: Relative Perceived Product Advantage, Perceived Product Complexity, Compatibility with digital travel research sources, and the adopter’s Innovativeness towards mobile applications. Specific characteristics in order to identify Local Wander’s early users, the so called Innovators, were detected giving indications for further necessary company market research. Findings showed that the diffusion of innovation framework is a helpful tool for start-ups’ prospective decision making and market entry strategy planning.

Functionalization of dendrimers for improved gene delivery to mesenchymal stem cell

Disease, injury, and age problems compromise human quality of life and continuously motivate the search for new and more efficacious therapeutic approaches. The field of Tissue Regeneration and Engineering has greatly evolved over the last years, mainly due to the combination of the important advances verified in Biomaterials Science and Engineering with those of Cell and Molecular Biology. In particular, a new and promising area arose – Nanomedicine – that takes advantage of the extremely small size and especial chemical and physical properties of Nanomaterials, offering powerful tools for health improvement. Research on Stem Cells, the self-renewing progenitors of body tissues, is also challenging to the medical and scientific communities, being expectable the appearance of new and exciting stem cell-based therapies in the next years. The control of cell behavior (namely, of cell proliferation and differentiation) is of key importance in devising strategies for Tissue Regeneration and Engineering. Cytokines, growth factors, transcription factors and other signaling molecules, most of them proteins, have been identified and found to regulate and support tissue development and regeneration. However, the application of these molecules in long-term regenerative processes requires their continuous presence at high concentrations as they usually present short half-lives at physiological conditions and may be rapidly cleared from the body. Alternatively, genes encoding such proteins can be introduced inside cells and be expressed using cell’s machinery, allowing an extended and more sustained production of the protein of interest (gene therapy). Genetic engineering of stem cells is particularly attractive because of their self-renewal capability and differentiation potential. For Tissue Regeneration and Engineering purposes, the patient’s own stem cells can be genetically engineered in vitro and, after, introduced in the body (with or without a scaffold) where they will not only modulate the behavior of native cells (stem cell-mediated gene therapy), but also directly participate in tissue repair. Cells can be genetically engineered using viral and non-viral systems. Viruses, as a result of millions of years of evolution, are very effective for the delivery of genes in several types of cells, including cells from primary sources. However, the risks associated with their use (like infection and immunogenic reactions) are driving the search for non-viral systems that will efficiently deliver genetic material into cells. Among them, chemical methods that are promising and being investigated use cationic molecules as carriers for DNA. In this case, gene delivery and gene expression level remain relatively low when primary cells are used. The main goal of this thesis was to develop and assess the in vitro potential of polyamidoamine (PAMAM) dendrimers based carriers to deliver genes to mesenchymal stem cells (MSCs). PAMAM dendrimers are monodispersive, hyperbranched and nanospherical molecules presenting unique characteristics that make them very attractive vehicles for both drug and gene delivery. Although they have been explored for gene delivery in a wide range of cell lines, the interaction and the usefulness of these molecules in the delivery of genes to MSCs remains a field to be explored. Adult MSCs were chosen for the studies due to their potential biomedical applications (they are considered multipotent cells) and because they present several advantages over embryonic stem cells, such as easy accessibility and the inexistence of ethical restrictions to their use. This thesis is divided in 5 interconnected chapters. Chapter I provides an overview of the current literature concerning the various non-viral systems investigated for gene delivery in MSCs. Attention is devoted to physical methods, as well as to chemical methods that make use of polymers (natural and synthetic), liposomes, and inorganic nanoparticles as gene delivery vectors. Also, it summarizes the current applications of genetically engineered mesenchymal stem cells using non-viral systems in regenerative medicine, with special focus on bone tissue regeneration. In Chapter II, the potential of native PAMAM dendrimers with amine termini to transfect MSCs is evaluated. The level of transfection achieved with the dendrimers is, in a first step, studied using a plasmid DNA (pDNA) encoding for the β-galactosidase reporter gene. The effect of dendrimer’s generation, cell passage number, and N:P ratio (where N= number of primary amines in the dendrimer; P= number of phosphate groups in the pDNA backbone) on the level of transfection is evaluated, being the values always very low. In a second step, a pDNA encoding for bone morphogenetic protein-2, a protein that is known for its role in MSCs proliferation and differentiation, is used. The BMP-2 content produced by transfected cells is evaluated by an ELISA assay and its effect on the osteogenic markers is analyzed through several classical assays including alkaline phosphatase activity (an early marker of osteogenesis), osteocalcin production, calcium deposition and mineralized nodules formation (late osteogenesis markers). Results show that a low transfection level is enough to induce in vitro osteogenic differentiation in MSCs. Next, from Chapter III to Chapter V, studies are shown where several strategies are adopted to change the interaction of PAMAM dendrimers with MSCs cell membrane and, as a consequence, to enhance the levels of gene delivery. In Chapter III, generations 5 and 6 of PAMAM dendrimers are surface functionalized with arginine-glycine-aspartic acid (RGD) containing peptides – experiments with dendrimers conjugated to 4, 8 and 16 RGD units were performed. The underlying concept is that by including the RGD integrin-binding motif in the design of the vectors and by forming RGD clusters, the level of transfection will increase as MSCs highly express integrins at their surface. Results show that cellular uptake of functionalized dendrimers and gene expression is enhanced in comparison with the native dendrimers. Furthermore, gene expression is dependent on both the electrostatic interaction established between the dendrimer moiety and the cell surface and the nanocluster RGD density. In Chapter IV, a new family of gene delivery vectors is synthesized consisting of a PAMAM dendrimer (generation 5) core randomly linked at the periphery to alkyl hydrophobic chains that vary in length and number. Herein, the idea is to take advantage of both the cationic nature of the dendrimer and the capacity of lipids to interact with biological membranes. These new vectors show a remarkable capacity for internalizing pDNA, being this effect positively correlated with the –CH2– content present in the hydrophobic corona. Gene expression is also greatly enhanced using the new vectors but, in this case, the higher efficiency is shown by the vectors containing the smallest hydrophobic chains. Finally, chapter V reports the synthesis, characterization and evaluation of novel gene delivery vectors based on PAMAM dendrimers (generation 5) conjugated to peptides with high affinity for MSCs membrane binding - for comparison, experiments are also done with a peptide with low affinity binding properties. These systems present low cytotoxicity and transfection efficiencies superior to those of native dendrimers and partially degraded dendrimers (Superfect®, a commercial product). Furthermore, with this biomimetic approach, the process of gene delivery is shown to be cell surface receptor-mediated. Overall, results show the potential of PAMAM dendrimers to be used, as such or modified, in Tissue Regeneration and Engineering. To our knowledge, this is the first time that PAMAM dendrimers are studied as gene delivery vehicles in this context and using, as target, a cell type with clinical relevancy. It is shown that the cationic nature of PAMAM dendrimers with amine termini can be synergistically combined with surface engineering approaches, which will ultimately result in suitable interactions with the cytoplasmic membrane and enhanced pDNA cellular entry and gene expression. Nevertheless, the quantity of pDNA detected inside cell nucleus is always very small when compared with the bigger amount reaching cytoplasm (accumulation of pDNA is evident in the perinuclear region), suggesting that the main barrier to transfection is the nuclear membrane. Future work can then be envisaged based on the versatility of these systems as biomedical molecular materials, such as the conjugation of PAMAM dendrimers to molecules able to bind nuclear membrane receptors and to promote nuclear translocation.