Prison-Based Dog Training Programs: Standard Protocol

Across the United States, the number of prison-based dog training programs (PDPs) has increased substantially over the past several years. Currently, there are approximately 255 PDPs across 47 states that operate in a variety of correctional settings; however, there is little information available on how to successfully develop and implement a PDP. As a result, the research team from the Institute for Human-Animal Connection (IHAC) has developed a standard protocol to help guide PDP development and implementation. This report identifies common practices of PDPs and incorporates both general and context-specific recommendations that were gathered from interviews with PDP staff, relevant literature, and content experts. In total, 21 interviews with 20 programs were conducted. PDPs were asked about several program features, including policies and procedures, key personnel, funding, materials, physical spaces, supervision and monitoring, safety considerations, animal welfare, handler selection and training, and program benefits. This report highlights the benefits of PDPs to dogs, humans, prisons, local communities, and society as a whole and identifies challenges related to funding, staffing, and operating in a correctional setting. Findings from the protocol point to the importance of planning, staffing, communication, internal support, and training curriculum in successful program implementation

Development of the research lifecycle model for library services

Can the niche services of individual librarians across multiple libraries be developed into a suite of standard services available to all scientists that support the entire research lifecycle

A Team Approach to Library Services for Interdisciplinary Science

In the summer of 2011, a group of five librarians from the University of North Carolina at Chapel Hill (UNC-CH) Health Sciences and Kenan Science Libraries formed the Health and Natural Sciences (HNS) team to discuss library services and methods of service delivery to scientific researchers. The team’s charge was to determine what services subject librarians were currently providing to their respective constituencies, what services were most important to researchers, and how to develop individual specialties into a suite of standard services that could be offered to all scientists and clinicians across the university. The team tackled these questions with a multifaceted approach that led to the development of a new service model based on the research lifecycle

“You must first save her life”: community perceptions towards induced abortion and postabortion care in North and South Kivu, Democratic Republic of the Congo

Structural barriers such as a restrictive legal environment, limited medical resources, and high costs inhibit access to safe abortion in the Democratic Republic of the Congo (DRC); these barriers are exacerbated by two decades of conflict. Socio-normative barriers further complicate access to safe abortion and post-abortion care (PAC) in DRC, where fear of abortion-related stigma may lead women to avoid PAC services. Programme partners support the Ministry of Health to provide good quality contraceptive and PAC services in North and South Kivu, DRC. This paper presents results from focus group discussions that explored community members’ attitudes towards women who induce abortion and their care-seeking behaviour in programme areas. Results indicate that while abortion stigma was widespread, community members’ attitudes towards women who induced abortions were not one-dimensional. Although they initially expressed negative opinions regarding women who induced abortion, beliefs became more nuanced as discussion shifted to the specific situations that could motivate a woman to do so. For example, many considered it understandable that a woman would induce abortion after rape: perhaps unsurprising, given the prevalence of conflict-related sexual violence in this area. While community members believed that fear of stigma or associated negative social consequences dissuaded women from seeking PAC, a majority believed that all women should have access to life-saving PAC. This commitment to ensuring that women who induced abortion have access to PAC, in addition to the professed acceptability of induced abortion in certain situations, indicates that there could be an opening to destigmatise abortion access in this context

Re-evaluation of the Fijianolide/Laulimalide Chemotype Suggests an Alternate Mechanism of Action for C-15/C-20 Analogs.

Herein, we report on naturally derived microtubule stabilizers with activity against triple negative breast cancer (TNBC) cell lines, including paclitaxel, fijianolide B/laulimalide (3), fijianolide B di-acetate (4), and two new semisynthetic analogs of 3, which include fijianolide J (5) and fijianolide L (6). Similar to paclitaxel, compound 3 demonstrated classic microtubule stabilizing activity with potent (GI50 = 0.7–17 nM) antiproliferative efficacy among the five molecularly distinct TNBC cell lines. Alternatively, compounds 5 or 6, generated from oxidation of C-20 or C-15 and C-20 respectively, resulted in a unique profile with reduced potency (GI50 = 4–9 μM), but improved efficacy in some lines, suggesting a distinct mechanism of action. The C-15, C-20 di-acetate, and dioxo modifications on 4 and 6 resulted in compounds devoid of classic microtubule stabilizing activity in biochemical assays. While 4 also had no detectable effect on cellular microtubules, 6 promoted a reorganization of the cytoskeleton resulting in an accumulation of microtubules at the cell periphery. Compound 5, with a single C-20 oxo substitution, displayed a mixed phenotype, sharing properties of 3 and 6. These results demonstrate the importance of the C-15/C-20 chiral centers, which appear to be required for the potent microtubule stabilizing activity of this chemotype and that oxidation of these sites promotes unanticipated cytoskeletal alterations that are distinct from classic microtubule stabilization, likely through a distinct mechanism of action

Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus

Funder: NHLI FoundationFunder: NIHR Imperial Biomedical Research Centre; FundRef: http://dx.doi.org/10.13039/501100013342Funder: National Heart Lung and Blood InstituteFunder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Funder: National Institute of Biomedical Imaging and Bioengineering; FundRef: http://dx.doi.org/10.13039/100000070Funder: Gates Cambridge ScholarshipFunder: NIH/OXCAM FellowshipObjectives: Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE. Methods: Proteomic/phosphoproteomic analyses were performed in healthy control (HC) normal density neutrophils (NDNs), SLE NDNs and autologous SLE LDGs. The biophysical properties of these neutrophil subsets were analysed by real-time deformability cytometry and lattice light-sheet microscopy. A two-dimensional endothelial flow system and a three-dimensional microfluidic microvasculature mimetic (MMM) were used to decouple the contributions of cell surface mediators and biophysical properties to neutrophil trafficking, respectively. Results: Proteomic and phosphoproteomic differences were detected between HC and SLE neutrophils and between SLE NDNs and LDGs. Increased abundance of type 1 interferon-regulated proteins and differential phosphorylation of proteins associated with cytoskeletal organisation were identified in SLE LDGs relative to SLE NDNs. The cell surface of SLE LDGs was rougher than in SLE and HC NDNs, suggesting membrane perturbances. While SLE LDGs did not display increased binding to endothelial cells in the two-dimensional assay, they were increasingly retained/trapped in the narrow channels of the lung MMM. Conclusions: Modulation of the neutrophil proteome and distinct changes in biophysical properties are observed alongside differences in neutrophil trafficking. SLE LDGs may be increasingly retained in microvasculature networks, which has important pathogenic implications in the context of lupus organ damage and small vessel vasculopathy

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Genome-Wide Association Study of Peripheral Artery Disease

Background: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status. Methods: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status. Results: We identified 5 genome-wide significant (P-associationPeer reviewe