Interaction design and emotional wellbeing

The World Health Organisation has concluded that emotional wellbeing is fundamental to our quality of life. It enables us to experience life as meaningful and is an essential component of social cohesion, peace and stability in the living environment [21]. This workshop will bring together a diverse community to consolidate existing knowledge and identify new opportunities for research on technologies designed to support emotional wellbeing. The workshop will examine uses of technology in mental health settings, but will also consider the importance of emotional needs in physical healthcare and wellbeing more generally. The design of technology to provide social support and to extend traditional care networks will be key workshop themes

Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2

Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite the availability of animal models for HSV-2 infection, little is known regarding the mechanism of immune induction within the vaginal mucosa. Here, we examined the cell types responsible for the initiation of protective Th1 immunity to HSV-2. Intravaginal inoculation of HSV-2 led to a rapid recruitment of submucosal dendritic cells (DCs) to the infected epithelium. Subsequently, CD11c+ DCs harboring viral peptides in the context of MHC class II molecules emerged in the draining lymph nodes and were found to be responsible for the stimulation of IFNγ secretion from HSV-specific CD4+ T cells. Other antigen-presenting cells including B cells and macrophages did not present viral peptides to T cells in the draining lymph nodes. Next, we assessed the relative contribution to immune generation by the Langerhans cells in the vaginal epithelium, the submucosal CD11b+ DCs, and the CD8α+ lymph node DCs. Analysis of these DC populations from the draining lymph nodes revealed that only the CD11b+ submucosal DCs, but not Langerhans cell–derived or CD8α+ DCs, presented viral antigens to CD4+ T cells and induced IFNγ secretion. These results demonstrate a previously unanticipated role for submucosal DCs in the generation of protective Th1 immune responses to HSV-2 in the vaginal mucosa, and suggest their importance in immunity to other sexually transmitted diseases

Reasons for non-suicidal self-harm in adult male offenders with and without borderline personality traits

The presented study aimed to advance understanding of the reasons for non-suicidal self-harm (NSSH) in adult male offenders, with and without borderline personality traits. 179 offenders completed self-report measures of NSSH and other clinical constructs, with 42 being identified as having self-harmed. Results were consistent with past research and supported the relative importance of intrapersonal over interpersonal functions, but also highlight that self-harm is performed rarely for one type of reason. The results also show that the presence of borderline personality traits increases the likelihood of endorsing a range of interpersonal reasons. These findings highlight the importance of understanding the range of reasons for engaging in NSSH to help manage the behaviour within the priso

Neoadjuvant Therapy of Pancreatic Cancer: The Emerging Paradigm?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140013/1/onco0192-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140013/2/onco0192.pd

Down-regulation of PLCγ2-β-catenin pathway promotes activation and expansion of myeloid-derived suppressor cells in cancer

Myeloid-derived suppressor cells (MDSCs) favor tumor promotion, mainly by suppressing antitumor T cell responses in many cancers. Although the mechanism of T cell inhibition is established, the pathways leading to MDSC accumulation in bone marrow and secondary lymphoid organs of tumor-bearing hosts remain unclear. We demonstrate that down-regulation of PLCγ2 signaling in MDSCs is responsible for their aberrant expansion during tumor progression. PLCγ2(−/−) MDSCs show stronger immune-suppressive activity against CD8(+) T cells than WT MDSCs and potently promote tumor growth when adoptively transferred into WT mice. Mechanistically, PLCγ2(−/−) MDSCs display reduced β-catenin levels, and restoration of β-catenin expression decreases their expansion and tumor growth. Consistent with a negative role for β-catenin in MDSCs, its deletion in the myeloid population leads to MDSC accumulation and supports tumor progression, whereas expression of β-catenin constitutively active reduces MDSC numbers and protects from tumor growth. Further emphasizing the clinical relevance of these findings, MDSCs isolated from pancreatic cancer patients show reduced p-PLCγ2 and β-catenin levels compared with healthy controls, similar to tumor-bearing mice. Thus, for the first time, we demonstrate that down-regulation of PLCγ2–β-catenin pathway occurs in mice and humans and leads to MDSC-mediated tumor expansion, raising concerns about the efficacy of systemic β-catenin blockade as anti-cancer therapy

Effect of 3-Dimensional Virtual Reality Models for Surgical Planning of Robotic-Assisted Partial Nephrectomy on Surgical Outcomes: A Randomized Clinical Trial.

Importance: Planning complex operations such as robotic-assisted partial nephrectomy requires surgeons to review 2-dimensional computed tomography or magnetic resonance images to understand 3-dimensional (3-D), patient-specific anatomy. Objective: To determine surgical outcomes for robotic-assisted partial nephrectomy when surgeons reviewed 3-D virtual reality (VR) models during operative planning. Design, Setting, and Participants: A single-blind randomized clinical trial was performed. Ninety-two patients undergoing robotic-assisted partial nephrectomy performed by 1 of 11 surgeons at 6 large teaching hospitals were prospectively enrolled and randomized. Enrollment and data collection occurred from October 2017 through December 2018, and data analysis was performed from December 2018 through March 2019. Interventions: Patients were assigned to either a control group undergoing usual preoperative planning with computed tomography and/or magnetic resonance imaging only or an intervention group where imaging was supplemented with a 3-D VR model. This model was viewed on the surgeon\u27s smartphone in regular 3-D format and in VR using a VR headset. Main Outcomes and Measures: The primary outcome measure was operative time. It was hypothesized that the operations performed using the 3-D VR models would have shorter operative time than those performed without the models. Secondary outcomes included clamp time, estimated blood loss, and length of hospital stay. Results: Ninety-two patients (58 men [63%]) with a mean (SD) age of 60.9 (11.6) years were analyzed. The analysis included 48 patients randomized to the control group and 44 randomized to the intervention group. When controlling for case complexity and other covariates, patients whose surgical planning involved 3-D VR models showed differences in operative time (odds ratio [OR], 1.00; 95% CI, 0.37-2.70; estimated OR, 2.47), estimated blood loss (OR, 1.98; 95% CI, 1.04-3.78; estimated OR, 4.56), clamp time (OR, 1.60; 95% CI, 0.79-3.23; estimated OR, 11.22), and length of hospital stay (OR, 2.86; 95% CI, 1.59-5.14; estimated OR, 5.43). Estimated ORs were calculated using the parameter estimates from the generalized estimating equation model. Referent group values for each covariate and the corresponding nephrometry score were summed across the covariates and nephrometry score, and the sum was exponentiated to obtain the OR. A mean of the estimated OR weighted by sample size for each nephrometry score strata was then calculated. Conclusions and Relevance: This large, randomized clinical trial demonstrated that patients whose surgical planning involved 3-D VR models had reduced operative time, estimated blood loss, clamp time, and length of hospital stay. Trial Registration: ClinicalTrials.gov identifiers (1 registration per site): NCT03334344, NCT03421418, NCT03534206, NCT03542565, NCT03556943, and NCT03666104

Natural history and ecological effects on the establishment and fate of Florida carpenter ant cadavers infected by the parasitic manipulator Ophiocordyceps camponoti‐floridani

Ophiocordyceps fungi manipulate the behaviour of their ant hosts to produce a summit disease phenotype, thereby establishing infected ant cadavers onto vegetation at elevated positions suitable for fungal growth and transmission. Multiple environmental and ecological factors have been proposed to shape the timing, positioning and outcome of these manipulations. We conducted a long-term field study of Ophiocordyceps camponoti-floridani infections of Camponotus floridanus ants—the Florida zombie ants. We propose and refine hypotheses on the factors that shape infection outcomes by tracking the occurrence of and fungal growth from hundreds of ant cadavers. We modelled and report these data in relation to weather, light, vegetation and attack by hyperparasites. We investigated environmental factors that could affect the occurrence and location of newly manipulated ant cadavers. New cadaver occurrence was preferentially biased towards epiphytic Tillandsia bromeliads, canopy openness and summer weather conditions (an interactive effect of temperature, humidity and precipitation). Furthermore, we suggest that incident light at the individual cadaver level reflects microhabitat choice by manipulated ants or selective pressure on cadaver maintenance for conditions that improve fungal survival. We also asked which environmental conditions affect fungal fitness. Continued fungal development of reproductive structures and putative transmission increased with moist weather conditions (interaction of humidity and precipitation) and canopy openness, while being reduced by hyperparasitic mycoparasite infections. Moreover, under the most open canopy conditions, we found an atypical Ophiocordyceps growth morphology that could represent a plastic response to conditions influenced by high light levels. Taken together, we explore general trends and the effects of various ecological conditions on host and parasite disease outcomes in the Florida zombie ant system. These insights from the field can be used to inform experimental laboratory setups that directly test the effects of biotic and abiotic factors on fungus–ant interactions or aim to uncover underlying molecular mechanisms. Read the free Plain Language Summary for this article on the Journal blog

Jaundice: an important, poorly recognized risk factor for diminished survival in patients with adenocarcinoma of the head of the pancreas

AbstractObjectivesJaundice impairs cellular immunity, an important defence against the dissemination of cancer. Jaundice is a common mode of presentation in pancreatic head adenocarcinoma. The purpose of this study was to determine whether there is an association between preoperative jaundice and survival in patients who have undergone resection of such tumours.MethodsThirty possible survival risk factors were evaluated in a database of over 400 resected patients. Univariate analysis was used to determine odds ratio for death. All factors for which a P‐value of <0.30 was obtained were entered into a multivariate analysis using the Cox model with backward selection.ResultsPreoperative jaundice, age, positive node status, poor differentiation and lymphatic invasion were significant indicators of poor outcome in multivariate analysis. Absence of jaundice was a highly favourable prognostic factor. Interaction emerged between jaundice and nodal status. The benefit conferred by the absence of jaundice was restricted to patients in whom negative node status was present. Five‐year overall survival in this group was 66%. Jaundiced patients who underwent preoperative stenting had a survival advantage.ConclusionsPreoperative jaundice is a negative risk factor in adenocarcinoma of the pancreas. Additional studies are required to determine the exact mechanism for this effect

Novel pulsatile-release microparticles for single-injection vaccination

Many controlled release devices are designed to achieve near zero-order release kinetics, however for some applications, such as vaccination, non-continuous or pulsatile release is desired. Such pulsatile release systems may enable the creation of single-injection vaccines that eliminate the need for subsequent booster immunizations by spontaneously releasing antigen at time points that correspond to normal vaccination regimens. This would be especially important in the developing world where a lack of consistent access to healthcare contributes to approximately 1.5 million vaccine-preventable deaths each year.1 Here we present the fabrication and characterization of biodegradable core-shell microparticles that exhibit pulsatile release kinetics due to their unique structure. These particles are produced using a novel fabrication process that combines soft lithography, picoliter dispensing, optical alignment, and a gentle heat-based sintering step to generate microparticles with a biodegradable polymeric shell surrounding an antigen-filled core. By altering the composition (e.g. copolymer ratio or molecular weight) of the poly(lactic-co-glycolic acid) shell, particles can be tuned to release discrete pulses of a model antigen at times ranging from four days to two months. This fabrication method is also compatible with sensitive biologics, such as the inactivated polio virus, which retains \u3e80% of its antigenicity after encapsulation. Further, because the shell of the particle is physically separated from the core, these particles can be filled with any aqueous vaccine solution without affecting release kinetics and be easily scaled via massively parallel fabrication. As a result, these particles have exciting potential as single-injection vaccines that fully mimic the antigen presentation profile of traditional bolus injections administered over the course of months or years. Please click Additional Files below to see the full abstract