Nanobody-liposomes as novel cancer vaccine platform to efficiently stimulate T cell immunity.

Cancer vaccines can be utilized in combination with checkpoint inhibitors to optimally stimulate the anti-tumor immune response. Uptake of vaccine antigen by antigen presenting cells (APCs) is a prerequisite for T cell priming, but often relies on non-specific mechanisms. Here, we have developed a novel vaccination strategy consisting of cancer antigen-containing liposomes conjugated with CD169- or DC-SIGN-specific nanobodies (single domain antibodies) to achieve specific uptake by APCs. Our studies demonstrate efficient nanobody liposome uptake by human and murine CD169+ and DC-SIGN+ APCs in vitro and in vivo when compared to control liposomes or liposomes with natural ligands for CD169 and DC-SIGN. Uptake of CD169 nanobody liposomes resulted in increased T cell activation by human APCs and stimulated naive T cell priming in mouse models. In conclusion, while nanobody liposomes have previously been utilized to direct drugs to tumors, here we show that nanobody liposomes can be applied as vaccination strategy that can be extended to other receptors on APCs in order to elicit a potent immune response against tumor antigens.

Does the innate relative size of the humeral head and glenoid affect the risk of anterior shoulder instability?

BACKGROUND: Bony lesions after shoulder dislocation reduce the joint contact area and increase the risk of recurrent instability. It is unknown whether the innate relative sizes of the humeral head and glenoid may predispose patients to shoulder instability. This study evaluated whether anterior shoulder instability is associated with a larger innate humeral head/glenoid ratio (IHGR). METHODS: We evaluated CT scans of 40 shoulders with anterior shoulder instability and 48 controls. We measured axial humeral head diameter and glenoid diameter following native contours, discarding any bony lesions, and calculated IHGR by dividing both diameters. Multivariate logistic regression determined whether the IHGR, corrected for age and gender as potential confounders, was associated with anterior shoulder instability. RESULTS: Mean IHGR was 1.48 ± 0.23 in the group with anterior shoulder instability and 1.42 ± 0.20 in the group without anterior shoulder instability. Measurements for axial humeral head and axial glenoid diameters demonstrated excellent intra-rater reliability (ICC range: 0.94-0.95). IHGR was not significantly associated with anterior shoulder instability (OR = 1.105, 95%CI = 0.118-10.339, p = 0.930). DISCUSSION: The innate ratio of humeral head and glenoid diameters was not significantly associated with anterior shoulder instability in this retrospective sample of 88 shoulder CT scans.

Microscopic characterization of defect structure in RDX crystals.

Three batches of the commercial energetic material RDX, as received from various production locations and differing in sensitivity towards shock initiation, have been characterized with different microscopic techniques in order to visualize the defect content in these crystals. The RDX crystals are embedded in an epoxy matrix and cross-sectioned. By a treatment of grinding and polishing of the crystals, the internal defect structure of a multitude of energetic crystals can be visualized using optical microscopy, scanning electron microscopy and confocal scanning laser microscopy. Earlier optical micrographs of the same crystals immersed in a refractive index matched liquid could visualize internal defects, only not in the required detail. The combination of different microscopic techniques allows for a better characterization of the internal defects, down to inclusions of approximately 0.5 µm in size. The defect structure can be correlated to the sensitivity towards a high-amplitude shock wave of the RDX crystals embedded in a polymer bonded explosive. The obtained experimental results comprise details on the size, type and quantity of the defects. These details should provide modellers with relevant and realistic information for modelling defects in energetic materials and their effect on the initiation and propagation of shock waves in PBX formulations.

Helping the female partners of men abusing alcohol: a comparison of three treatments.

AIM: To evaluate the effectiveness of three approaches to assisting the female partners of male problem drinkers with the stress imposed by the male's drinking. DESIGN: Participants were assigned randomly via random number tables to one of three treatment conditions: supportive counselling, stress management or alcohol-focused couples therapy. SETTING: The intervention took place at the Behaviour Research and Therapy Centre (BRTC), The University of Queensland. This research and training centre offers outpatient psychology services to the community. PARTICIPANTS: Sixty-one married women whose husbands drank heavily. Participants reported protracted alcohol problems, severe impact of alcohol on social functioning and severe marital distress. MEASUREMENT: The women's stress, alcohol consumption by the male, and relationship functioning were assessed at pre- and post-treatment and at 6-month follow-up. INTERVENTIONS: All three treatments involved 15 1-hour sessions with the woman. In the alcohol-focused couple therapy, attempts were made to engage the man in these sessions. RESULTS: Contrary to our predictions, there were few differences between the treatments. All three treatments were associated with reductions in the women's reported stress, with trends for somewhat greater reduction in the women's stress in the stress management and alcohol-focused couples therapy conditions than for supportive counselling. None of the treatments produced clinically significant reductions in men's drinking or relationship distress. CONCLUSION: The treatments ease stresses and burden but do not improve drinking or relationships. Limited power in the design restricted the capacity to detect differential treatment effects.

Individual psychopathology and marital distress. Analyzing the association and implications for therapy.

This article is a review of the association of individual and marital problems. The focus is on depression, alcohol abuse, anxiety disorders, and the functional psychoses, each of which interact with marital distress in important ways. Although the causal connections between these disorders and marital distress are complex and only particularly understood, the available evidence shows that individuals' and couples' problems often exacerbate each other. Consequently, regardless of whether the initial presentation is individual or couple focused, there is routinely a need to assess both individual and relationship functioning. Couples therapy, and in particular behavioral couples therapy (BCT), is an important element of effective treatment of depression, alcohol abuse, anxiety disorders, and the functional psychoses. The integration of couple and individual therapy presents a number of clinical challenges, and in concluding this article the authors provide guidelines for managing these challenges.

Attorney-case manager collaboration in the conservatorship of older adults.

The complex issues of long-term care are everchanging, with no one discipline having the corner on all the intricate options, regulations, and ethical choices that often confront an aging person. This is most critical when a person's incompetence requires the appointment of a conservator or guardian. When the probate court finds it necessary to appoint a conservator/guardian for an older adult, and family or other informal caregivers are unavailable or unable to assume the role, the responsibility is often delegated to an attorney. However, an attorney's expertise is in the field of law, not necessarily in the complex and intricate long-term health care system. Maintaining a mentally incompetent and functionally disabled person in the safest and least restrictive environment is demanding. It requires a thorough knowledge and understanding of the physical and emotional changes associated with the aging process, an area of expertise of long-term care case managers. Combining the clinical proficiency of the case manager with the legal and financial expertise of the attorney benefits the conserved older adult. This article illustrates this collaborative approach to long-term care through the use of several case histories.

Parent and adolescent perceptions of family functioning: a comparison of clinic and non-clinic families.

In this paper two studies are reported which compare (a) the perceptions of family functioning held by clinic and non-clinic adolescents, and (b) the perceptions of family functioning held by adolescents and their mothers in clinic and non-clinic families. In Study 1, matched group of clinic and non-clinic adolescents were compared on their responses to a 30-item scale (ICPS) designed to measure three factors of family functioning: Intimacy (high vs. low), Parenting Style (democratic vs. controlled) and Conflict (high vs. low). Clinic and non-clinic adolescents were also compared on their responses to a multi-dimensional measure of adolescent self-concept. Although there was little difference between the two groups of adolescents in terms of their perceptions of family functioning, there were strong relationships between the self-concept variables and the family functioning variables. In Study 2, comparisons were made between the perceptions of family functioning held by mothers and adolescents for both clinical and non-clinic families. There were no differences between the two groups of adolescents in terms of their perceptions of family functioning, although there were clear differences between the two groups of mothers. In addition, clinic adolescents and their mothers did not differ in their perceptions of the family, whereas adolescents in the non-clinic group saw their families significantly as less intimate and more conflicted than did their mothers.

The impact of chronic childhood illness on family stress: a comparison between autism and cystic fibrosis.

The study compared the different patterns of stress reported by mothers of children with either a chronic physical illness (cystic fibrosis), a chronic psychological disorder (autism), and children without a physical or psychological disorder. Twenty-four mothers from each of these three groups completed the Questionnaire on Resources and Stress Short Form (Holroyd & Guthrie, 1986). Each clinical group exhibited different patterns of stressful response consistent with the nature of the disorder and the requirements of care imposed on the families. Autism was found to contribute significantly more to family stress than did cystic fibrosis. The number of children in the family was not a significant variable. Implications for the development of family intervention programs are discussed.