Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro

Oocyte control of granulosa and theca cell function may be mediated by several growth factors via a local feedback loop(s) between these cell types. This study examined both the role of oocyte-secreted factors on granulosa and thecal cells, cultured independently and in co-culture, and the effect of stem cell factor (SCF); a granulosa cell derived peptide that appears to have multiple roles in follicle development. Granulosa and theca cells were isolated from 2–6 mm healthy follicles of mature porcine ovaries and cultured under serum-free conditions, supplemented with: 100 ng/ml LR3 IGF-1, 10 ng/ml insulin, 100 ng/ml testosterone, 0–10 ng/ml SCF, 1 ng/ml FSH (granulosa), 0.01 ng/ml LH (theca) or 1 ng/ml FSH and 0.01 ng/ml LH (co-culture) and with/without oocyte conditioned medium (OCM) or 5 oocytes. Cells were cultured in 96 well plates for 144 h, after which viable cell numbers were determined. Medium was replaced every 48 h and spent medium analysed for steroids. Oocyte secreted factors were shown to stimulate both granulosa cell proliferation (P < 0.001) and oestradiol production (P < 0.001) by granulosa cells throughout culture. In contrast, oocyte secreted factors suppressed granulosa cell progesterone production after both 48 and 144 hours (P < 0.001). Thecal cell numbers were increased by oocyte secreted factors (P = 0.02), together with a suppression in progesterone and androstenedione synthesis after 48 hours (P < 0.001) and after 144 hours (P = 0.02), respectively. Oocyte secreted factors also increased viable cell numbers (P < 0.001) in co-cultures together with suppression of progesterone (P < 0.001) and oestradiol (P < 0.001). In granulosa cell only cultures, SCF increased progesterone production in a dose dependent manner (P < 0.001), whereas progesterone synthesis by theca cells was reduced in a dose dependent manner (P = 0.002). Co-cultured cells demonstrated an increase in progesterone production with increasing SCF dose (P < 0.001) and an increase in oestradiol synthesis at the highest dose of SCF (100 ng/ml). In summary, these findings demonstrate the presence of a co-ordinated paracrine interaction between somatic cells and germ cells, whereby oocyte derived signals interact locally to mediate granulosa and theca cell function. SCF has a role in modulating this local interaction. In conclusion, the oocyte is an effective modulator of granulosa-theca interactions, one role being the inhibition of luteinization

Do Policy Implementation Support Programmes Work? The Case of the Care Act 2014

Context: Policy implementation is an often overlooked stage when policy is introduced. Too often the result is policy failure caused by overly optimistic expectations, implementation in dispersed governance, inadequate collaborative policy-making, and the vagaries of the political cycle. The Care Act 2014 introduced the most significant change in social care law in England for 60 years. Given the complexity of the changes, the Department of Health and Social Care and its key partners introduced an Implementation Support Programme (ISP) to increase the likelihood of smooth implementation. Objective: To assess the impact of the ISP on local implementation of the Care Act and develop a framework for understanding the requirements of a successful ISP. Methods: Analysis was undertaken of the relevant theoretical and conceptual literature in addition to a review of support programmes for other national policies. The empirical study of the impact of the Care Act’s ISP, conducted in six local authorities, focused on three levels of activity that shaped outcomes: national, regional and local. Data were collected through interviews with key stakeholders at each level. Findings: The ISP enjoyed several successes including: helping to secure policy legitimacy, developing stakeholder engagement, sustaining political support, and ensuring the readiness of local implementation agencies. Limitations: The empirical research was confined to six English local authorities which limits drawing general conclusions applicable to the whole country. Implications: Little evidence exists on the value of ISPs. The research goes some way to closing the gap and offers provisional messages on their value to policy-makers and practitioners

The Ursinus Weekly, December 9, 1971

Gulf Oil Corporation awards scholarships to U.C. science scholars • Scrounge Lounge opens; Provides place for chat • Traditional banquet takes on a new look • Seven Ursinus seniors named to Who\u27s who • Memorial service: Dr. John Vorrath • Ecological concern group sponsors recycling project • Editorial: False alarm; Scrounge! • Focus: Stan Talley • Messiah sung tonight; Annual U.C. tradition • Faculty portrait: Mr. Walter Marsteller • Administration answers • Ursinus presents gift of $1,500 to Collegeville • Francis Davis speaks at Sigma Xi meeting • Slumming it • Critic\u27s choice: Thanksgiving, Marcus Welby M.D., Jamie Brockett and hayrides • Spotlight: Mr. Philip Harvey • Bears even record; Future looks good • Their work is never done • Letter to the editor • Soccer season closes: 4 wins, 7 losses, 3 ties • USGA notes • Outing Club braves cold • Ursinus Harriers place second in Middle Atlantic Conferencehttps://digitalcommons.ursinus.edu/weekly/1114/thumbnail.jp

LMDA Newsletter, July 1, 2016

Contents include: Letter from the Editor; A Message from our LMDA President; Canadian Fellows: Vicki Stroich & Bob White in Conversation; Freelancing Across America: On the Road with Heather Helinsky; From Producing to Freelancing: Artistic Leaders Jayne Wenger & Mead Hunter; Freelancing in Canada: David Geary Talks Shop & Indigenous Dramaturgy; Early Career Projects: Anna Woodruff Collaborates with Melis Aker; Benches We Have Shared: Elizabeth Bennett & Liz Engelman Talk Life after Institutional Dramaturgy; Upcoming Events.https://soundideas.pugetsound.edu/lmdanewsletter/1008/thumbnail.jp

Reframing human rights: the global network of moral conservative homeschooling activists

In this article, we investigate the composition and actions of a principled issue network within the field of human rights that uses rights-claims to pursue traditionalist goals: the moral conservative pro-homeschooling network. We analyse the rising importance of homeschooling within the global moral conservative movement and examine the transnationalization of pro-homeschooling advocacy. We show that the transnational homeschooling advocacy network, while not successful in court cases, has managed to establish home education as part of a global conservative agenda and has made incursions into redefining the terms of the debate within international organizations. Moral conservative homeschooling advocates use a vocabulary of rights and freedoms, and even of moral pluralism, but in the conservative reading human rights are reframed and used to defend a pro-family agenda that establishes the patriarchal family as the ultimate source of authority and the primary carrier of rights

Walk with Me: a protocol for a pilot RCT of a peer-led walking programme to increase physical activity in inactive older adults

Background: Levels of physical activity decline with age. Some of the most disadvantaged individuals in society, such as those from lower socio-economic position, are also the most inactive. Increasing physical activity levels, particularly among those most inactive, is a public health priority. Peer-led physical activity interventions may offer a model to increase physical activity in the older adult population. This study aims to test the feasibility of a peer-led, multicomponent physical activity intervention in socio-economically disadvantaged community dwelling older adults. Methods: The Medical Research Council framework for developing and evaluating complex interventions will be used to design and test the feasibility of a randomised controlled trial (RCT) of a multicomponent peer-led physical activity intervention. Data will be collected at baseline, immediately after the intervention (12 weeks) and 6 months after baseline measures. The pilot RCT will provide information on recruitment of peer mentors and participants and attrition rates, intervention fidelity, and data on the variability of the primary outcome (minutes of moderate to vigorous physical activity measured with an accelerometer). The pilot trail will also assess the acceptability of the intervention and identify potential resources needed to undertake a definitive study. Data analyses will be descriptive and include an evaluation of eligibility, recruitment, and retention rates. The findings will be used to estimate the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders to identify areas of success and necessary improvements. Discussion: This paper describes the protocol for the ‘Walk with Me’ pilot RCT which will provide the information necessary to inform the design and delivery of a fully powered trial should the Walk with Me intervention prove feasible

Peer-led walking programme to increase physical activity in inactive 60- to 70-year-olds: Walk with Me pilot RCT

Background Levels of physical activity decline with age. Some of the most disadvantaged individuals in society, such as those with a lower rather than a higher socioeconomic position, are also the most inactive. Peer-led physical activity interventions may offer a model to increase physical activity in these older adults and thus help reduce associated health inequalities. This study aims to develop and test the feasibility of a peer-led, multicomponent physical activity intervention in socioeconomically disadvantaged community-dwelling older adults. Objectives The study aimed to develop a peer-led intervention through a rapid review of previous peer-led interventions and interviews with members of the target population. A proposed protocol to evaluate its effectiveness was tested in a pilot randomised controlled trial (RCT). Design A rapid review of the literature and the pilot study informed the intervention design; a pilot RCT included a process evaluation of intervention delivery. Setting Socioeconomically disadvantaged communities in the South Eastern Health and Social Care Trust and the Northern Health and Social Care Trust in Northern Ireland. Participants Fifty adults aged 60–70 years, with low levels of physical activity, living in socioeconomically disadvantaged communities, recruited though community organisations and general practices. Interventions ‘Walk with Me’ is a 12-week peer-led walking intervention based on social cognitive theory. Participants met weekly with peer mentors. During the initial period (weeks 1–4), each intervention group participant wore a pedometer and set weekly step goals with their mentor’s support. During weeks 5–8 participants and mentors met regularly to walk and discuss step goals and barriers to increasing physical activity. In the final phase (weeks 9–12), participants and mentors continued to set step goals and planned activities to maintain their activity levels beyond the intervention period. The control group received only an information booklet on active ageing. Main outcome measures Rates of recruitment, retention of participants and completeness of the primary outcome [moderate- and vigorous-intensity physical activity measured using an ActiGraph GT3X+ accelerometer (ActiGraph, LLC, Pensacola, FL, USA) at baseline, 12 weeks (post intervention) and 6 months]; acceptability assessed through interviews with participants and mentors. Results The study planned to recruit 60 participants. In fact, 50 eligible individuals participated, of whom 66% (33/50) were female and 80% (40/50) were recruited from general practices. At 6 months, 86% (43/50) attended for review, 93% (40/43) of whom returned valid accelerometer data. Intervention fidelity was assessed by using weekly step diaries, which were completed by both mentors and participants for all 12 weeks, and checklists for the level of delivery of intervention components, which was high for the first 3 weeks (range 49–83%). However, the rate of return of checklists by both mentors and participants diminished thereafter. Outcome data indicate that a sample size of 214 is required for a definitive trial. Limitations The sample was predominantly female and somewhat active. Conclusions The ‘Walk with Me’ intervention is acceptable to a socioeconomically disadvantaged community of older adults and a definitive RCT to evaluate its effectiveness is feasible. Some modifications are required to ensure fidelity of intervention delivery is optimised. Future research needs to identify methods to recruit males and less active older adults into physical activity interventions

Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course