Long-term prevalence and predictors of prolonged grief disorder amongst bereaved cancer caregivers: A cohort study

Context: The short-term impact of prolonged grief disorder (PGD) following bereavement is well documented. The longer term sequelae of PGD however are poorly understood, possibly unrecognized, and may be incorrectly attributed to other mental health disorders and hence undertreated. Objectives: The aims of this study were to prospectively evaluate the prevalence of PGD three years post bereavement and to examine the predictors of long-term PGD in a population-based cohort of bereaved cancer caregivers. Methods: A cohort of primary family caregivers of patients admitted to one of three palliative care services in Melbourne, Australia, participated in the study (n = 301). Sociodemographic, mental health, and bereavement-related data were collected from the caregiver upon the patient\u27s admission to palliative care (T1). Further data addressing circumstances around the death and psychological health were collected at six (T2, n = 167), 13 (T3, n = 143), and 37 months (T4, n = 85) after bereavement. Results: At T4, 5% and 14% of bereaved caregivers met criteria for PGD and subthreshold PGD, respectively. Applying the total PGD score at T4, linear regression analysis found preloss anticipatory grief measured at T1 and self-reported coping measured at T2 were highly statistically significant predictors (both p \u3c 0.0001) of PGD in the longer term. Conclusion: For almost 20% of caregivers, the symptoms of PGD appear to persist at least three years post bereavement. These findings support the importance of screening caregivers upon the patient\u27s admission to palliative care and at six months after bereavement to ascertain their current mental health. Ideally, caregivers at risk of developing PGD can be identified and treated before PGD becomes entrenched

Prospects for the cavity-assisted laser cooling of molecules

Cooling of molecules via free-space dissipative scattering of photons is thought not to be practicable due to the inherently large number of Raman loss channels available to molecules and the prohibitive expense of building multiple repumping laser systems. The use of an optical cavity to enhance coherent Rayleigh scattering into a decaying cavity mode has been suggested as a potential method to mitigate Raman loss, thereby enabling the laser cooling of molecules to ultracold temperatures. We discuss the possibility of cavity-assisted laser cooling particles without closed transitions, identify conditions necessary to achieve efficient cooling, and suggest solutions given experimental constraints. Specifically, it is shown that cooperativities much greater than unity are required for cooling without loss, and that this could be achieved via the superradiant scattering associated with intracavity self-localization of the molecules. Particular emphasis is given to the polar hydroxyl radical (OH), cold samples of which are readily obtained from Stark deceleration.Comment: 18 pages, 10 figure

Recombinant Listeria promotes tumor rejection by CD8+ T cell-dependent remodeling of the tumor microenvironment.

Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1+PD1loCD62L- CD8+ T cells. These IFNγ-producing effector CD8+ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to an inflamed microenvironment that was characterized by a decrease in regulatory T cells (Treg) levels, a proinflammatory cytokine milieu, and the shift of M2 macrophages to an inducible nitric oxide synthase (iNOS)+CD206- M1 phenotype. Remarkably, these LADD-Ag-induced tumor-specific T cells persisted for more than 2 months after primary tumor challenge and rapidly controlled secondary tumor challenge. Our results indicate that the striking antitumor efficacy observed in mice with LADD-based immunotherapy stems from TME remodeling which is a direct consequence of eliciting potent, systemic tumor-specific CD8+ T cells

Exploring the impact, value and limitations of reflective practice groups for clergy in a Church in Wales diocese

This is an Accepted Manuscript of an article published by Taylor & Francis in Mental Health, Religion and Culture on 3rd September 2020, available online: https://doi.org/10.1080/13674676.2020.1789571This research explores the impact, value and limitations of reflective practice groups for Clergy in a Church in Wales diocese. The aims were to explore what participants of reflective practice groups experience as the impact, value and limitations of their groups, and to better understand any implications for delivery of reflective practice groups for Clergy. Two focus groups comprising of the participants from two reflective practice groups from a diocese in the Church in Wales were interviewed, and the data analysed using Interpretative Phenomenological Analysis. Two superordinate themes emerged along with ten subordinate themes. The key findings are that the participants of both groups clearly found them to be a valuable experience and self-defined the impact on their ministries as: creating more reflective clergy; developing greater wisdom; building and gaining affirmed strategies that they could take back into relationships within their parishes; enabling a different perspective to be gained on management expectations; development of self-preservation strategies for coping with those expectations; improvement in practice and relationships within their work; improving their priestly skills; managing boundaries more appropriately; approaching meetings more positively; managing situations in more helpful ways; and discerning what God may be saying in certain situations

Characteristics of effective collaborative care for treatment of depression: a systematic review and meta-regression of 74 randomised controlled trials

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.BACKGROUND: Collaborative care is a complex intervention based on chronic disease management models and is effective in the management of depression. However, there is still uncertainty about which components of collaborative care are effective. We used meta-regression to identify factors in collaborative care associated with improvement in patient outcomes (depressive symptoms) and the process of care (use of anti-depressant medication). METHODS AND FINDINGS: Systematic review with meta-regression. The Cochrane Collaboration Depression, Anxiety and Neurosis Group trials registers were searched from inception to 9th February 2012. An update was run in the CENTRAL trials database on 29th December 2013. Inclusion criteria were: randomised controlled trials of collaborative care for adults ≥18 years with a primary diagnosis of depression or mixed anxiety and depressive disorder. Random effects meta-regression was used to estimate regression coefficients with 95% confidence intervals (CIs) between study level covariates and depressive symptoms and relative risk (95% CI) and anti-depressant use. The association between anti-depressant use and improvement in depression was also explored. Seventy four trials were identified (85 comparisons, across 21,345 participants). Collaborative care that included psychological interventions predicted improvement in depression (β coefficient -0.11, 95% CI -0.20 to -0.01, p = 0.03). Systematic identification of patients (relative risk 1.43, 95% CI 1.12 to 1.81, p = 0.004) and the presence of a chronic physical condition (relative risk 1.32, 95% CI 1.05 to 1.65, p = 0.02) predicted use of anti-depressant medication. CONCLUSION: Trials of collaborative care that included psychological treatment, with or without anti-depressant medication, appeared to improve depression more than those without psychological treatment. Trials that used systematic methods to identify patients with depression and also trials that included patients with a chronic physical condition reported improved use of anti-depressant medication. However, these findings are limited by the observational nature of meta-regression, incomplete data reporting, and the use of study aggregates.NIH

Measurement of Intracellular Fluorescence of Human Monocytes Relative to Oxidative Metabolism

Human monocytes (MN) produce O2â and H2O2 when stimulated by agonists. Dichlorofluorescin diacetate (DCFHâ DA) has been used as a substrate for measuring intracellular oxidant production in neutrophils. DCFHâ DA is hydrolyzed by esterases to dichlorofluorescin (DCFH), which is trapped within the cell. This nonfluorescent molecule is then oxidized to fluorescent dichlorofluorescin (DCF) by action of cellular oxidants. DCFHâ DA can not be appreciably oxidized to a fluorescent state without prior hydrolysis. We have examined the utility of DCFHâ DA for the assessment of monocyte oxidative responses. The levels of intracellular fluorescence measured by flow cytometry were considerably less than expected from reported levels of O2â â production or chemiluminescence assays. Compared with neutrophils, monocytes produced minimal increases in DCF fluorescence after stimulation with phorbol myristate acetate as measured by flow cytometry, but both cell types showed increases in fluorescence when bulk cell suspensions were measured by spectrofluorometry. To determine the intracellular location of the DCFH, bulk fluorescence measurements were made on both whole and sonicated cell preparations. When intact mononuclear cells were preloaded with DCFHâ DA, then sonicated and oxidized with added excess H2O2, the increase in fluorescence was only 30% of the fluorescence of mononuclear cell sonicates to which DCFHâ DA was added and oxidized in a similar manner. These results suggest that a portion of the DCFHâ DA incorporated by intact cells, is not susceptible to oxidation by the added H2O2. Addition of NaOH to induce hydrolysis of any residual DCFHâ DA in the sonicates of DCFHâ DAâ loaded intact mononuclear cells resulted in a further increase in fluorescence upon addition of H2O2, suggesting that a significant portion of the DCFHâ DA was not hydrolyzed despite ample uptake of this dye by these cells. In contrast, no further increase in fluorescence was observed in sonicates of DCFHâ DAâ loaded intact neutrophils, suggesting complete hydrolysis of all incorporated DCFHâ DA to DCFH. When monocytes were allowed to phagocytose DCFHâ DAâ loaded Staphylococcus aureus, intracellular fluorescence was measurable by flow cytometry, indicating intracellular oxidation of the fluorochromes. We therefore propose that in monocytes the mechanism of intracellular processing of these fluorochromes differs from that in neutrophils owing to differences in intracellular localization of fluorochromes, site of oxidant production, and/or accessibility of the DCFHâ DA to esterolysis.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141433/1/jlb0304.pd

Benefits and resource implications of family meetings for hospitalized palliative care patients: research protocol.

BACKGROUND:Palliative care focuses on supporting patients diagnosed with advanced, incurable disease; it is 'family centered', with the patient and their family (the unit of care) being core to all its endeavours. However, approximately 30-50% of carers experience psychological distress which is typically under recognised and consequently not addressed. Family meetings (FM) are recommended as a means whereby health professionals, together with family carers and patients discuss psychosocial issues and plan care; however there is minimal empirical research to determine the net effect of these meetings and the resources required to implement them systematically. The aims of this study were to evaluate: (1) if family carers of hospitalised patients with advanced disease (referred to a specialist palliative care in-patient setting or palliative care consultancy service) who receive a FM report significantly lower psychological distress (primary outcome), fewer unmet needs, increased quality of life and feel more prepared for the caregiving role; (2) if patients who receive the FM experience appropriate quality of end-of-life care, as demonstrated by fewer hospital admissions, fewer emergency department presentations, fewer intensive care unit hours, less chemotherapy treatment (in last 30 days of life), and higher likelihood of death in the place of their choice and access to supportive care services; (3) the optimal time point to deliver FM and; (4) to determine the cost-benefit and resource implications of implementing FM meetings into routine practice.METHODS:Cluster type trial design with two way randomization for aims 1-3 and health economic modeling and qualitative interviews with health for professionals for aim 4.DISCUSSION:The research will determine whether FMs have positive practical and psychological impacts on the family, impacts on health service usage, and financial benefits to the health care sector. This study will also provide clear guidance on appropriate timing in the disease/care trajectory to provide a family meeting.<br/

A Method for Data-Driven Simulations of Evolving Solar Active Regions

We present a method for performing data-driven simulations of solar active region formation and evolution. The approach is based on magnetofriction, which evolves the induction equation assuming the plasma velocity is proportional to the Lorentz force. The simulations of active region coronal field are driven by temporal sequences of photospheric magnetograms from the Helioseismic Magnetic Imager (HMI) instrument onboard the Solar Dynamics Observatory (SDO). Under certain conditions, the data-driven simulations produce flux ropes that are ejected from the modeled active region due to loss of equilibrium. Following the ejection of flux ropes, we find an enhancement of the photospheric horizontal field near the polarity inversion line. We also present a method for the synthesis of mock coronal images based on a proxy emissivity calculated from the current density distribution in the model. This method yields mock coronal images that are somewhat reminiscent of images of active regions taken by instruments such as SDO's Atmospheric Imaging Assembly (AIA) at extreme ultraviolet wavelengths.Comment: Accepted to ApJ; comments/questions related to this article are welcome via e-mail, even after publicatio

Rigorous mean field model for CPA: Anderson model with free random variables

A model of a randomly disordered system with site-diagonal random energy fluctuations is introduced. It is an extension of Wegner's $n$-orbital model to arbitrary eigenvalue distribution in the electronic level space. The new feature is that the random energy values are not assumed to be independent at different sites but free. Freeness of random variables is an analogue of the concept of independence for non-commuting random operators. A possible realization is the ensemble of at different lattice-sites randomly rotated matrices. The one- and two-particle Green functions of the proposed hamiltonian are calculated exactly. The eigenstates are extended and the conductivity is nonvanishing everywhere inside the band. The long-range behaviour and the zero-frequency limit of the two-particle Green function are universal with respect to the eigenvalue distribution in the electronic level space. The solutions solve the CPA-equation for the one- and two-particle Green function of the corresponding Anderson model. Thus our (multi-site) model is a rigorous mean field model for the (single-site) CPA. We show how the Llyod model is included in our model and treat various kinds of noises.Comment: 24 pages, 2 diagrams, Rev-Tex. Diagrams are available from the authors upon reques

Physiological effects of major genes affecting ovulation rate in sheep

Genetic mutations with major effects on ovulation rate in sheep were recently identified in two genes of the transforming growth factor (TGFβ) superfamily and a TGFβ receptor, namely bone morphogenetic protein 15 (BMP15), otherwise known as the growth differentiation factor 9b (GDF9b), GDF9 and activin-like kinase 6 (ALK6) otherwise known as the BMP receptor type IB (BMPRIB). Animals homozygous for the BMP15 or GDF9 mutations are anovulatory whereas animals heterozygous for BMP15 or GDF9 or heterozygous or homozygous for ALK6 have higher than normal ovulation rates. Immunisation of ewes against BMP15 or GDF9 shows that both are essential for normal follicular development and control of ovulation rate. Common features of fertile animals with the BMP15, ALK6 (and possibly GDF9) mutations are changes in oocyte development during early preantral follicular growth, earlier maturation of granulosa cells and ovulation of mature follicles at smaller diameters. In summary, these findings have led to a new paradigm in reproductive biology, namely that the oocyte plays a key role in regulating the ovulation rate