210 Goodbyes: Lessons from Making Final Grants and Ending Grantee Relationships

These are words an organization never likes to hear, but let's be honest: funding relationships eventually come to an end. Sometimes, the end is carefully planned -- a funding initiative with a limited life span, a foundation that decides to spend down. At other times, it's a mutual decision when funder and grantee discover that their goals are not aligned or that their partnership has simply run its course. It might even be a surprise -- such as when the stock market or the legislative appropriations process take a turn that leaves the funder with fewer assets than anticipated.No matter what the reason, the end of a funding relationship can be cordial and affirmative, advancing and demonstrating the grantee's resilience. But it can also be turbulent or even catastrophic, damaging relationships, reputations, and the grantee organization's prospects for future success. The different outcomes depend, surprisingly, less on the magnitude of funding lost and more on the degree of care taken by both partners to prepare for the change -- and to anticipate the challenges and opportunities it will bring

Understanding Fundraising Fundamentals - Including the Role of Consultants

Fundraising success involves a combination of knowledge, skills, systems, and consistent practices. Fundraising campaigns that take a systematic approach and put fundamentals in place in an appropriate sequence have a better chance of success. Projects risk failure when they start with donor prospecting, fundraising software, or communications materials when the fundamentals are not set. Here is an introduction to fundraising fundamentals, featuring eight key activities

Who Presents Where? A Population-Based Analysis of Socio-Demographic Inequalities in Head and Neck Cancer Patients' Referral Routes

Head and neck cancers (HNC) are often late stage at diagnosis; stage is a major determinant of prognosis. The urgent cancer referral pathway (two week wait; 2WW) within England's National Health Service aims to reduce time to diagnosis. We investigated factors associated with HNC route to diagnosis. Data were obtained from the English population-based cancer registry on 66,411 primary invasive HNCs (ICD C01-14 and C31-32) diagnosed 2006-2014. Multivariable logistic regression determined the likelihood of different diagnosis routes by patients' demographic and clinical characteristics. Significant socio-demographic inequalities were observed. Emergency presentations declined over time and 2WW increased. Significant socio-demographic inequalities were observed. Non-white patients, aged over 65, residing in urban areas with advanced disease, were more likely to have emergency presentations. White males aged 55 and older with an oropharynx cancer were more likely to be diagnosed via 2WW. Higher levels of deprivation were associated with both emergency and 2WW routes. Dental referral was more likely in women, with oral cancers and lower stage disease. Despite the decline over time in emergency presentation and the increased use of 2WW, socio-demographic variation is evident in routes to diagnosis. Further work exploring the reasons for these inequalities, and the consequences for patients' care and outcomes, is urgently required

Molecular footprints reveal the impact of the protective HLA-A*03 allele in hepatitis C virus infection

Background and aims: CD8 T cells are central to the control of hepatitis C virus (HCV) although the key features of a successful CD8 T cell response remain to be defined. In a cohort of Irish women infected by a single source, a strong association between viral clearance and the human lecucocyte (HLA)-A*03 allele has been described, and the aim of this study was to define the protective nature of the associated CD8 T cell response. Methods: A sequence-led approach was used to identify HLA-A*03-restricted epitopes. We examine the CD8 T cell response associated with this gene and address the likely mechanism underpinning this protective effect in this special cohort, using viral sequencing, T cell assays and analysis of fitness of viral mutants. Results: A strong 'HLA footprint' in a novel NS3 epitope (TVYHGAGTK) was observed. A lysine (K) to arginine (R) substitution at position 9 (K1088R) was seen in a significant number of A*03-positive patients (9/12) compared with the control group (1/33, p=0.0003). Threonine (T) was also substituted with alanine (A) at position 8 (T1087A) more frequently in A*03-positive patients (6/12) compared with controls (2/33, p=0.01), and the double substitution of TK to AR was also observed predominantly in HLA-A*03- positive patients (p=0.004). Epitope-specific CD8 T cell responses were observed in 60% of patients three decades after exposure and the mutants selected in vivo impacted on recognition in vitro. Using HCV replicons matched to the viral sequences, viral fitness was found to be markedly reduced by the K1088R substitution but restored by the second substitution T1087A. Conclusions: It is proposed that at least part of the protective effect of HLA-A*03 results from targeting of this key epitope in a functional site: the requirement for two mutations to balance fitness and escape provides an initial host advantage. This study highlights the potential protective impact of common HLA-A alleles against persistent viruses, with important implications for HCV vaccine studies

Investigating the Extent to Which Patients Should Control Access to Patient Records for Research: A Deliberative Process Using Citizens� Juries

BackgroundThe secondary use of health data for research raises complex questions of privacy and governance. Such questions are ill-suited to opinion polling where citizens must choose quickly between multiple-choice answers based on little information.ObjectiveThe aim of this project was to extend knowledge about what control informed citizens would seek over the use of health records for research after participating in a deliberative process using citizens' juries.MethodsTwo 3-day citizens' juries, of 17 citizens each, were convened to reflect UK national demographics from 355 eligible applicants. Each jury addressed the mission "To what extent should patients control access to patient records for secondary use?" Jurors heard from and questioned 5 expert witnesses (chosen either to inform the jury, or to argue for and against the secondary use of data), interspersed with structured opportunities to deliberate among themselves, including discussion and role-play. Jurors voted on a series of questions associated with the jury mission, giving their rationale. Individual views were polled using questionnaires at the beginning and at end of the process.ResultsAt the end of the process, 33 out of 34 jurors voted in support of the secondary use of data for research, with 24 wanting individuals to be able to opt out, 6 favoring opt in, and 3 voting that all records should be available without any consent process. When considering who should get access to data, both juries had very similar rationales. Both thought that public benefit was a key justification for access. Jury 1 was more strongly supportive of sharing patient records for public benefit, whereas jury 2 was more cautious and sought to give patients more control. Many jurors changed their opinion about who should get access to health records: 17 people became more willing to support wider information sharing of health data for public benefit, whereas 2 moved toward more patient control over patient records.ConclusionsThe findings highlight that, when informed of both risks and opportunities associated with data sharing, citizens believe an individual's right to privacy should not prevent research that can benefit the general public. The juries also concluded that patients should be notified of any such scheme and have the right to opt out if they so choose. Many jurors changed their minds about this complex policy question when they became more informed. Many, but not all, jurors became less skeptical about health data sharing, as they became better informed of its benefits and risks

The effect of HIV infection and HCV viremia on Inflammatory Mediators and Hepatic Injury-The Women\u27s Interagency HIV Study.

Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18), ART-treated HIV-controlled (ARTc, n = 20), uncontrolled on anti-retroviral therapy (ARTuc, n = 21) and elite HIV controllers (Elite, n = 20). All were HCV seroreactive and had either resolved (HCV RNA-; \u3c50IU/mL) or had chronic HCV infection (HCV RNA+). In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI) was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection

Investigating the Extent to Which Patients Should Control Access to Patient Records for Research: A Deliberative Process Using Citizens� Juries (Preprint)

BACKGROUND The secondary use of health data for research raises complex questions of privacy and governance. Such questions are ill-suited to opinion polling where citizens must choose quickly between multiple-choice answers based on little information. OBJECTIVE The aim of this project was to extend knowledge about what control informed citizens would seek over the use of health records for research after participating in a deliberative process using citizens’ juries. METHODS Two 3-day citizens’ juries, of 17 citizens each, were convened to reflect UK national demographics from 355 eligible applicants. Each jury addressed the mission “To what extent should patients control access to patient records for secondary use?” Jurors heard from and questioned 5 expert witnesses (chosen either to inform the jury, or to argue for and against the secondary use of data), interspersed with structured opportunities to deliberate among themselves, including discussion and role-play. Jurors voted on a series of questions associated with the jury mission, giving their rationale. Individual views were polled using questionnaires at the beginning and at end of the process. RESULTS At the end of the process, 33 out of 34 jurors voted in support of the secondary use of data for research, with 24 wanting individuals to be able to opt out, 6 favoring opt in, and 3 voting that all records should be available without any consent process. When considering who should get access to data, both juries had very similar rationales. Both thought that public benefit was a key justification for access. Jury 1 was more strongly supportive of sharing patient records for public benefit, whereas jury 2 was more cautious and sought to give patients more control. Many jurors changed their opinion about who should get access to health records: 17 people became more willing to support wider information sharing of health data for public benefit, whereas 2 moved toward more patient control over patient records. CONCLUSIONS The findings highlight that, when informed of both risks and opportunities associated with data sharing, citizens believe an individual’s right to privacy should not prevent research that can benefit the general public. The juries also concluded that patients should be notified of any such scheme and have the right to opt out if they so choose. Many jurors changed their minds about this complex policy question when they became more informed. Many, but not all, jurors became less skeptical about health data sharing, as they became better informed of its benefits and risks. </sec

Invasive carcinomas of the male breast: a morphologic study of the distribution of histologic subtypes and metastatic patterns in 778 cases

The current investigation was conducted to evaluate the proportional distribution of the various histologic subtypes (including newly recognized variants) of male breast carcinomas, to determine whether any histologic subtypes occur with a frequency that is markedly discordant with the expected frequencies from published data on parallel female breast tumors. We also aimed to document the distribution of malignancies metastatic to the breast. Seven hundred fifty-nine archived cases of primary invasive carcinoma involving the male breast were retrieved and subcategorized into histologic subtypes according to contemporary criteria. Six hundred forty-three (84.7%) tumors were pure infiltrating ductal carcinoma (IDC) not otherwise specified. The most common of the remainder included papillary carcinoma with invasion in the form of IDC (n = 34), mixed IDC and mucinous carcinoma (n = 26), and pure mucinous carcinoma (n = 21). In 19 cases, metastases from other sites involved the breast, most commonly (58%) cutaneous melanoma. Invasive carcinoma of the male breast appears to display a morphologic spectrum and distribution of histologic subtypes that is comparable to those of the female breast, with some expected variation. Compared with published experience on their female counterparts, there is a two-fold increase in the frequency of invasive papillary carcinoma in the male breast. Finally, the most common tumor metastatic to the male breast in this series was cutaneous melanoma