The interpersonal process model of intimacy, burden and communal motivation to care in a multinational group of informal caregivers

The interpersonal process model of intimacy suggests that intimacy within dyads develops when open communication from one dyad member is met with validating, understanding and caring responses from the other dyad member. Little is known about interpersonal processes between informal caregivers and care recipients in different illness contexts (i.e., coping with neurological, physical or other impairments/comorbidities) and relationship types (i.e., spouses, adult children and others), and how interpersonal processes are linked to the caregivers’ wellbeing. In this cross-sectional study, caregivers (N = 882) from nine countries reported on their open communication with care recipients, care recipients’ responsiveness, and caregivers’ wellbeing (i.e., intimacy, burden and communal motivation to care). Although caregivers of care recipients with neurological impairments and adult child caregivers reported lower mean levels of open communication and perceived responsiveness, similar mediating effects of perceived responsiveness between open communication and intimacy (effect = 0.05; CI95 = [0.04, 0.06]), burden (effect = −0.42; CI95 = [−0.49, −0.35]), and communal motivation to care (effect = 0.28; CI95 = [0.21, 0.36]) were reported across different illness contexts and relationship types. Only the negative relationship between perceived responsiveness and burden was stronger for spouses (b = −0.23, CI95 = [-0.26, −0.19]) than for adult children and others. Results suggest the interpersonal process model of intimacy may be used to identify caregivers at risk of poor wellbeing in different illness contexts and with different relationships with their care recipients. Lack of open communication and caregivers’ misperceptions of care recipients’ responsiveness may represent opportunities to intervene to enhance caregivers’ intimacy to the care recipients, communal motivation to care, and to decrease caregiver burden.</p

The ENTWINE iCohort Study, a multinational longitudinal web-based study of informal care

Informal care is a key pillar of long-term care provision across Europe and will likely play an even greater role in the future. Thus, research that enhances our understanding of caregiving experiences becomes increasingly relevant. The ENTWINE iCohort Study examines the personal, psychological, social, economic, and geographic factors that shape caregiving experiences. Here, we present the baseline cohort of the study and describe its design, recruitment methods, data collection procedures, measures, and early baseline findings. The study was conducted in nine countries: Germany, Greece, Ireland, Israel, Italy, the Netherlands, Poland, Sweden, and the United Kingdom. The study comprised a web- based longitudinal survey (baseline + 6-month follow-up) and optional weekly diary assessments, conducted separately with caregivers and care recipients. From 14 August 2020 to 31 August 2021, 1872 caregivers and 402 care recipients were enrolled at baseline. Participants were recruited via Facebook, and to a lesser extent via the study website or caregiver/patient organisations. Caregiver participants were predominantly female (87%) and primary caregivers (82%), with a median age of 55 years. A large proportion (80%) held at least post-secondary education, and two-thirds were married/partnered. Over half of the caregivers were employed (53%) and caring for a person with multiple chronic conditions (56%), and nearly three-quarters were caring for either a parent (42%) or a spouse/partner (32%). About three-quarters of care recipient participants were female (77%), not employed (74%), and had at least post-secondary education (77%), with a median age of 55 years. Over half of the care recipients were married/partnered (59%), receiving care primarily from their spouses/partners (61%), and diagnosed with multiple chronic conditions (57%). This study examining numerous potential influences on caregiving experiences provides an opportunity to better understand the multidimensional nature of these experiences. Such data could have implications for developing caregiving services and policies, and for future informal care research.<br/

Process sequence of soil aggregate formation disentangled through multi-isotope labelling

Microaggregates (250 µm) that resisted 60 J mL−1 ultrasonic dispersion. Afterwards, we assessed the C, N, Fe, and Si stable isotope composition in each size fraction. After four weeks we found a rapid build-up of stable macroaggregates comprising almost 50 % of soil mass in the treatment with plants and respective soil rooting, but only 5 % when plants were absent. The formation of these stable macroaggregates proceeded with time. Soil organic carbon (SOC) contents were elevated by 15 % in the large macroaggregates induced by plant growth. However, the recovery of EPS-derived 13C was below 20 % after 4 weeks, indicating rapid turnover in treatments both with and without plants. The remaining EPS-derived C was mainly found in macroaggregates when plants were present and in the occluded small microaggregates (<20 µm) when plants were absent. The excess of bacterial 15N closely followed the pattern of EPS-derived 13C (R2 = 0.72). In contrast to the organic gluing agents, the goethite-57Fe and montmorillonite-29Si were relatively equally distributed across all size fractions. Overall, microaggregates were formed within weeks. Roots enforced this process by stabilizing microaggregates within stable macroaggregates. As time proceeded the labelled organic components decomposed, while the labelled secondary oxides and clay minerals increasingly contributed to aggregate stabilization and turnover at the scale of months and beyond. Consequently, the well-known hierarchical organization of aggregation follows a clear chronological sequence of stabilization and turnover processes

Architecture of soil microaggregates: Advanced methodologies to explore properties and functions

The functions of soils are intimately linked to their three-dimensional pore space and the associated biogeochemical interfaces, mirrored in the complex structure that developed during pedogenesis. Under stress overload, soil disintegrates into smaller compound structures, conventionally named aggregates. Microaggregates (<250 µm) are recognized as the most stable soil structural units. They are built of mineral, organic, and biotic materials, provide habitats for a vast diversity of microorganisms, and are closely involved in the cycling of matter and energy. However, exploring the architecture of soil microaggregates and their linkage to soil functions remains a challenging but demanding scientific endeavor. With the advent of complementary spectromicroscopic and tomographic techniques, we can now assess and visualize the size, composition, and porosity of microaggregates and the spatial arrangement of their interior building units. Their combinations with advanced experimental pedology, multi-isotope labeling experiments, and computational approaches pave the way to investigate microaggregate turnover and stability, explore their role in element cycling, and unravel the intricate linkage between structure and function. However, spectromicroscopic techniques operate at different scales and resolutions, and have specific requirements for sample preparation and microaggregate isolation; hence, special attention must be paid to both the separation of microaggregates in a reproducible manner and the synopsis of the geography of information that originates from the diverse complementary instrumental techniques. The latter calls for further development of strategies for synlocation and synscaling beyond the present state of correlative analysis. Here, we present examples of recent scientific progress and review both options and challenges of the joint application of cutting-edge techniques to achieve a sophisticated picture of the properties and functions of soil microaggregates

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Having a creative day:understanding entrepreneurs’ daily idea generation through a recovery lens

Prior research has shown that trait creativity is important for becoming an entrepreneur and successful in business. We explore a new perspective by investigating how recovery from work stress influences entrepreneurs’ daily idea generation, a key aspect of creativity. Physio-logical and mental recovery enables the cognitive processes of creative problem-solving. Moreover, differences in mental recovery processes help to explain age-related changes in en-trepreneurs’ creativity. Multilevel analyses based on 415 daily data from 62 entrepreneurs support our predictions. Our study introduces a new “state” perspective to understanding en-trepreneurs’ creativity, and highlights the critical role of recovery processes for idea genera-tion

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The interpersonal process model of intimacy, burden and communal motivation to care in a multinational group of informal caregivers

The interpersonal process model of intimacy suggests that intimacy within dyads develops when open communication from one dyad member is met with validating, understanding and caring responses from the other dyad member. Little is known about interpersonal processes between informal caregivers and care recipients in different illness contexts (i.e., coping with neurological, physical or other impairments/comorbidities) and relationship types (i.e., spouses, adult children and others), and how interpersonal processes are linked to the caregivers’ wellbeing. In this cross-sectional study, caregivers (N = 882) from nine countries reported on their open communication with care recipients, care recipients’ responsiveness, and caregivers’ wellbeing (i.e., intimacy, burden and communal motivation to care). Although caregivers of care recipients with neurological impairments and adult child caregivers reported lower mean levels of open communication and perceived responsiveness, similar mediating effects of perceived responsiveness between open communication and intimacy (effect = 0.05; CI95 = [0.04, 0.06]), burden (effect = −0.42; CI95 = [−0.49, −0.35]), and communal motivation to care (effect = 0.28; CI95 = [0.21, 0.36]) were reported across different illness contexts and relationship types. Only the negative relationship between perceived responsiveness and burden was stronger for spouses (b = −0.23, CI95 = [-0.26, −0.19]) than for adult children and others. Results suggest the interpersonal process model of intimacy may be used to identify caregivers at risk of poor wellbeing in different illness contexts and with different relationships with their care recipients. Lack of open communication and caregivers’ misperceptions of care recipients’ responsiveness may represent opportunities to intervene to enhance caregivers’ intimacy to the care recipients, communal motivation to care, and to decrease caregiver burden.</p