Recruiting hard to reach populations to studies: breaking the silence: an example from a study that recruited people with dementia

Objective To share the challenges of recruiting people with dementia to studies, using experiences from one recently completed trial as an exemplar. Background Research publications always cite participant numbers but the effort expended to achieve the sample size is rarely reported, even when the study involved recruiting a hard to reach population. A multisite study of a psychosocial intervention for people with dementia illustrates the challenges. This study recruited 468 ‘dyads’ (a person with dementia and a family carer together) from 15 sites but the time taken to achieve this was longer than originally estimated. This led to a study extension and the need for additional sites. Recruitment data revealed that certain sites were more successful than others, but why? Can the knowledge gained be used to inform other studies? Methods Secondary analysis of routinely collected recruitment data from three purposefully selected sites was examined to understand the strategies used and identify successful approaches. Findings At all three sites, the pool of potential recruits funnelled to a few participants. It took two sites 18 months longer than the third to achieve recruitment numbers despite additional efforts. Explanations given by potential participants for declining to take part included ill health, reporting they were ‘managing’, time constraints, adjusting to a diagnosis of dementia and burden of study procedures. Conclusions Successful recruitment of people with dementia to studies, as one example of a hard to reach group, requires multiple strategies and close working between researchers and clinical services. It requires a detailed understanding of the needs and perspectives of the specific population and knowledge about how individuals can be supported to participate in research. Experiences of recruitment should be disseminated so that knowledge generated can be used to inform the planning and implementation of future research studies

Aperture Synthesis Imaging of V892 Tau and PV Cep: Disk Evolution

I present a study of two Herbig Ae stars that are in completely different evolutionary stages: V892 Tau and PV Cep. Using sub arc-second interferometric observations obtained with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at the 1.3 and 2.7 mm wavelengths, I have for the first time resolved their disks. I deduce that the 5 Myr old V892 Tau has a low dust opacity index $\beta$=1.1 and a disk mass of 0.03 \msun. These values correspond to the growth of its dust into large up to centimeters size structures. In contrast, the very young (a few 10$^5$yrs) PV Cep has a quite high opacity index $\beta$ =1.75 and a more massive disk 0.8 \msun. PV Cep has the youngest resolved disk around any Herbig Ae star. Unlike the youngest T Tauri and Class 0 stars, which contain large and processed grains, the young Herbig Ae star, PV Cep, disk contains ISM-like unprocessed dust. This suggests that PV Cep's dust evolution is slower than T Tauri stars'. I also present high spatial resolution interferometric observations of the PV Cep outflow. The outflow inclination is consistent with the orientation of the known Herbig-Haro flow in that region, HH315.Comment: 15 pages, Accepted for publication in Ap

Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation

Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo

Recruiting hard to reach populations to studies: breaking the silence: an example from a study that recruited people with dementia

Objective To share the challenges of recruiting people with dementia to studies, using experiences from one recently completed trial as an exemplar. Background Research publications always cite participant numbers but the effort expended to achieve the sample size is rarely reported, even when the study involved recruiting a hard to reach population. A multisite study of a psychosocial intervention for people with dementia illustrates the challenges. This study recruited 468 ‘dyads’ (a person with dementia and a family carer together) from 15 sites but the time taken to achieve this was longer than originally estimated. This led to a study extension and the need for additional sites. Recruitment data revealed that certain sites were more successful than others, but why? Can the knowledge gained be used to inform other studies? Methods Secondary analysis of routinely collected recruitment data from three purposefully selected sites was examined to understand the strategies used and identify successful approaches. Findings At all three sites, the pool of potential recruits funnelled to a few participants. It took two sites 18 months longer than the third to achieve recruitment numbers despite additional efforts. Explanations given by potential participants for declining to take part included ill health, reporting they were ‘managing’, time constraints, adjusting to a diagnosis of dementia and burden of study procedures. Conclusions Successful recruitment of people with dementia to studies, as one example of a hard to reach group, requires multiple strategies and close working between researchers and clinical services. It requires a detailed understanding of the needs and perspectives of the specific population and knowledge about how individuals can be supported to participate in research. Experiences of recruitment should be disseminated so that knowledge generated can be used to inform the planning and implementation of future research studies

Interactions between microenvironment and cancer cells in two animal models of bone metastasis

The preferential proliferation of cancer cells in the bone microenvironment is poorly characterised. Expression pattern of bone marrow and other organ microenvironment in contact with osteolytic (Walker W256) and osteoblastic (MatLyLu MLL) metastases were investigated. Fisher and Copenhagen rats received, respectively, W256 and MLL cells injection. Bone and soft tissues were analysed by immunochemistry for DKK1, cathepsin K, RANKL, MCSF or IL6 expression. Tartrate-resistant acid phosphatase (TRAcP)-positive cells were detected by a histoenzymatic technique. In bone, expressions of MCSF and DKK1 were shown in stromal cells of the bone marrow, in contact with metastatic foci of both tumours. Many stromal cells were found RANKL positive in the vicinity of the tumours. Cells expressing cathepsin K and multinucleated TRAcP+ cells were found in direct contact with trabeculae but also in bone marrow spaces near metastatic cells. In extraosseous tumours, cells in contact with malignant cells did not expressed DKK1, MCSF, cathepsin K and IL6. Some RANKL+ cells were found in the periphery of subcutaneous tumours but may represent Langerhans cells. Abnormal presence of TRAcP+ cells was never observed in the vicinity of malignant cells. Interaction between stromal and cancer cells induces the expression on the formers of characteristics leading to osteoclastogenesis only in the bone microenvironment

Hypoxia perturbs endothelium by re-organizing cellular actin architecture: Nitric oxide offers limited protection

Exposure to hypoxia causes structural changes in the endothelial cell (EC) monolayer that alter its permeability. There was a report earlier of impairment of nitric oxide (NO) production in endothelium. Intervention of NO in the altered cellular arrangements of actin cytoskeleton in endothelium for rectification of paracellular gaps in endothelium under hypoxia was observed. The present study demonstrates hypoxia inducing paracellular gaps in hypoxia exposed blood capillaries in chick embryo extra vascular model. Phalloidin staining confirmed significant polymerization of actin and unique cellular localization of the F-actin bands under hypoxia treatments. Addition of spermine NONOate (SPNO), a NO donor, or reoxygenation to endothelial monolayer attenuated hypoxia-mediated effects on endothelial permeability with partial recovery of endothelial integrity through actin remodeling. The present study indicates link of hypoxia-induced actin-associated cytoskeletal rearrangements and paracellular gaps in the endothelium with a low NO availability in the hypoxia milieu. The author concludes that NO confers protection against hypoxia-mediated cytoskeletal remodeling and endothelial leakiness

Pre-pandemic mental health and disruptions to healthcare, economic and housing outcomes during the COVID-19 pandemic: evidence from 12 UK longitudinal studies

Background: The COVID-19 pandemic has disrupted lives and livelihoods, and people already experiencing mental ill health may have been especially vulnerable. / Aims: Quantify mental health inequalities in disruptions to healthcare, economic activity and housing. / Method: We examined data from 59 482 participants in 12 UK longitudinal studies with data collected before and during the COVID-19 pandemic. Within each study, we estimated the association between psychological distress assessed pre-pandemic and disruptions since the start of the pandemic to healthcare (medication access, procedures or appointments), economic activity (employment, income or working hours) and housing (change of address or household composition). Estimates were pooled across studies. / Results: Across the analysed data-sets, 28% to 77% of participants experienced at least one disruption, with 2.3–33.2% experiencing disruptions in two or more domains. We found 1 s.d. higher pre-pandemic psychological distress was associated with (a) increased odds of any healthcare disruptions (odds ratio (OR) 1.30, 95% CI 1.20–1.40), with fully adjusted odds ratios ranging from 1.24 (95% CI 1.09–1.41) for disruption to procedures to 1.33 (95% CI 1.20–1.49) for disruptions to prescriptions or medication access; (b) loss of employment (odds ratio 1.13, 95% CI 1.06–1.21) and income (OR 1.12, 95% CI 1.06 –1.19), and reductions in working hours/furlough (odds ratio 1.05, 95% CI 1.00–1.09) and (c) increased likelihood of experiencing a disruption in at least two domains (OR 1.25, 95% CI 1.18–1.32) or in one domain (OR 1.11, 95% CI 1.07–1.16), relative to no disruption. There were no associations with housing disruptions (OR 1.00, 95% CI 0.97–1.03). / Conclusions: People experiencing psychological distress pre-pandemic were more likely to experience healthcare and economic disruptions, and clusters of disruptions across multiple domains during the pandemic. Failing to address these disruptions risks further widening mental health inequalities

Mental health inequalities in healthcare, economic, and housing disruption during COVID-19: an investigation in 12 longitudinal studies

Background: The COVID-19 pandemic and its associated virus suppression measures have disrupted lives and livelihoods, potentially exacerbating inequalities. People already experiencing mental ill-health may have been especially vulnerable to disruptions. / Aim: Investigate associations between pre-pandemic psychological distress and disruptions during the pandemic to (1) healthcare, economic activity, and housing, (2) cumulative disruptions and 3) whether these differ by age, sex, ethnicity or education. / Methods: Data were from 59,482 participants in 12 UK longitudinal adult population surveys with data collected both prior to and during the COVID-19 pandemic. Participants self-reported disruptions since the start of the pandemic to: healthcare (medication access, procedures, or appointments); economic activity (negative changes in employment, income or working hours); and housing (change of address or household composition). Logistic regression models were used within each study to estimate associations between pre-pandemic psychological distress scores and disruption outcomes. Findings were synthesised using a random effects meta-analysis with restricted maximum likelihood. / Results: Between one to two-thirds of study participants experienced at least one disruption during the pandemic, with 2.3-33.2% experiencing disruptions in 2 or more of the 3 domains examined. One standard deviation higher pre-pandemic psychological distress was associated with: (i) increased odds of any healthcare disruptions (OR=1.30; 95% CI: 1.20 to 1.40) with fully adjusted ORs ranging from 1.33 [1.20 to 1.49] for disruptions to prescriptions or medication access and 1.24 [1.09 to 1.41] for disruption to procedures; (ii) loss of employment (OR=1.13 [1.06 to 1.21]) and income (OR=1.12 [1.06 to 1.19]) and reductions in working hours/furlough (OR=1.05 [1.00 to 1.09]); (iii) no associations with housing disruptions (OR=1.00 [0.97 to 1.03]); and (iv) increased likelihood of experiencing a disruption in at least two domains (OR=1.25 [1.18 to 1.32]) or in one domain (OR=1.11 [1.07 to 1.16]) relative to experiencing no disruption. We did not find evidence of these associations differing by sex, ethnicity, education level, or age. / Conclusion: Those suffering from psychological distress before the pandemic were more likely to experience healthcare disruptions, economic disruptions related to unemployment and loss of income, and to clusters of disruptions across multiple domains during the pandemic. Considering mental ill-health was already unequally distributed in the UK population, the pandemic may exacerbate existing mental health inequalities. Individuals with poor mental health may need additional support to manage these pandemic-associated disruptions

H2CO and CH3OH abundances in the envelopes around low-mass protostars

This paper presents the third in a series of single-dish studies of molecular abundances in the envelopes around a large sample of 18 low-mass pre- and protostellar objects. It focuses on typical grain mantle products and organic molecules, including H2CO, CH3OH and CH3CN. With a few exceptions, all H2CO lines can be fit by constant abundances of 7e(-11)-8e(-9) throughout the envelopes if ortho- and para lines are considered independently. The current observational dataset does not require a large H2CO abundance enhancement in the inner warm regions, but this can also not be ruled out. Through comparison of the H2CO abundances of the entire sample, the H2CO ortho-para ratio is constrained to be 1.6+/-0.3 consistent with thermalization on grains at temperatures of 10-15 K. The H2CO abundances can be related to the empirical chemical network established on the basis of our previously reported survey of other species and is found to be closely correlated with that of the nitrogen-bearing molecules. These correlations reflect the freeze-out of molecules at low temperatures and high densities. An improved fit to the data is obtained with a `drop' abundance structure in which the abundance decrease when the temperature is lower than the evaporation temperature and the density high enough so that the timescale for depletion is less than the lifetime of the core. The derived abundance structures for CH3OH are consistent with a scenario where CH3OH probes the action of compact outflows on the envelopes, which is further supported by comparison to high frequency, high excitation CS J=10-9 and HDO line profiles. The extent to which the outflow dominates the abundance enhancements compared with the passively heated inner envelope depends on the filling factors of the two components in the observing beam.Comment: Accepted for publication in A&A. Abstract abridge