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Objective: This study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with noncentral geographic atrophy (GA). Design: ReCLAIM-2 was a prospective, phase II, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875). Subjects: Patients aged ≥55 years with ≥1 eye with dry AMD with GA were enrolled. Methods: Administration of daily subcutaneous elamipretide 40 mg was investigated in subjects for 48 weeks followed by a 4-week follow-up period. Main Outcome Measures: The primary efficacy end points were the mean change from baseline (BL) in low-luminance best-corrected visual acuity (LL BCVA) and the change in square root (Sqrt) converted GA area from BL as measured by OCT. Additional predefined end points included ellipsoid zone (EZ) integrity preservation assessment and categorical changes in LL BCVA. The primary safety end point was the incidence and severity of adverse events. Results: Of the 176 patients randomized, there were 117 and 59 patients in the elamipretide and placebo groups, respectively. Although elamipretide did not meet statistical significance for the primary end points (mean change in LL BCVA and mean change in Sqrt converted GA area), elamipretide produced a 43% reduction in the mean progression from BL in the macular percentage of total EZ attenuation/loss (i.e., complete loss of EZ band; nominal P = 0.0034) and 47% reduction in the mean progression of macular percentage of partial EZ attenuation/degradation (i.e., EZ-retinal pigment endothelium thickness of ≤20 microns; nominal P = 0.0040) versus placebo at week 48. Elamipretide treatment was also associated with significantly more patients experiencing a ≥10 letter gain in LL BCVA versus placebo (14.6% vs. 2.1%; nominal P = 0.0404). Adverse events were reported in 86% of those receiving elamipretide and 71% of the placebo group with the most common events being injection site reactions (e.g., pruritus, injection site pain, bruising, and erythema). Conclusions: While the primary end points were not met in this phase II study, elamipretide treatment was associated with a slowing of progressive EZ degradation/loss, a surrogate for photoreceptor damage. These findings have important clinical relevance since EZ attenuation/photoreceptor loss precedes and predicts the progressive pathological changes associated with vision loss and AMD. The EZ attenuation/loss end point will serve as the regulatory approved primary end point in the elamipretide phase III clinical development program. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cancer remains a prominent cause of mortality, accounting for approximately one-six of all deaths worldwide. The World Health Organization anticipates a rise in both cancer incidence and mortality rates, particularly in developing nations. In these regions, traditional herbal medicine plays a significant role in the treatment of various ailments, including tumors and cancers. Ethnobotanical studies conducted in the Kumasi region of Ghana have identified five medicinal plants, namely Pericopsis laxiflora (Benth. ex Baker.) Meeuwen., Mitragyna stipulosa (DC.) Kuntze., Cryptolepis nigrescens (Wennberg) L.Joubert. and Bruyns., Prosopsis africana (Guill. and Perr.) Taub. and Pterygota macrocarpa K.Schum, which are traditionally used for tumor management. Previous research articles have documented the ethnopharmacological activities of these plants. However, as far as we know, no preliminary in vitro cytotoxic screening using cervical (HELA), colorectal (RKO) and liver (HEPG2) human cancer cell lines has been conducted. In vitro cytotoxic activity of the aqueous and hydro-ethanol crude extracts derived from the five plants leaves and stembark was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) bioassay. The most promising extract was identified based on the lowest IC50 value. The cytotoxic effects of P. laxiflora and M. stipulosa extracts on all three cell lines were found to be minimal. However, extracts from P. africana and P. macrocarpa showed moderate inhibition of RKO cell viability. Among the extracts, the hydro-ethanol extract derived from C. nigrescens stembark (CSHE) displayed the highest cytotoxicity in vitro and was further subjected to bio-guided fractionation. The methanol fraction was identified to be the most active in all tested cell lines. The findings obtained from this study offer preclinical evidence for the traditional medicinal applications of P. africana, P. macrocarpa and C. nigrescens in the treatment of neoplastic conditions. Additionally, it proposes the need for further investigations into the potential antiproliferative properties of the methanol fraction from CSHE.

Immunotherapy, in the form of hematopoietic stem cell transplantation (HSCT), has been part of the standard of care in the treatment of acute leukemia for over 40 years. Trials evaluating novel immunotherapeutic approaches, such as targeting the programmed death-1 (PD-1) pathway, have unfortunately not yielded comparable results to those seen in solid tumors. Major histocompatibility complex (MHC) proteins are cell surface proteins essential for the adaptive immune system to recognize self versus non-self. MHC typing is used to determine donor compatibility when evaluating patients for HSCT. Recently, loss of MHC class II (MHC II) was shown to be a mechanism of immune escape in patients with acute myeloid leukemia after HSCT. Here we report that treatment with the tyrosine kinase inhibitor, dasatinib, and an anti-PD-1 antibody in preclinical models of Philadelphia chromosome positive B-cell acute lymphoblastic leukemia is highly active. The dasatinib and anti-PD-1 combination reduces tumor burden, is efficacious, and extends survival. Mechanistically, we found that treatment with dasatinib significantly increased MHC II expression on the surface of antigen-presenting cells (APC) in a tumor microenvironment-independent fashion and caused influx of APC cells into the leukemic bone marrow. Finally, the induction of MHC II may potentiate immune memory by impairing leukemic engraftment in mice previously cured with dasatinib, after re-inoculation of leukemia cells. In summary, our data suggests that anti-PD-1 therapy may enhance the killing ability of dasatinib via dasatinib driven APC growth and expansion and upregulation of MHC II expression, leading to antileukemic immune rewiring.

This article introduces and critically reflects upon the development of CiviAct – a multi-agency project that partners six anti-racist activist organisations and two universities in the North of England. CiviAct seeks to support and realise the benefits of youth and community-led civic action. It does this by: (i) financially resourcing the work of six anti-racist activist organisations; (ii) connecting those organisations with each other to create new opportunities for co-learning; and (iii) exploring new models of community-led university partnership. Based on insights derived from a 12-month development period (conducted throughout the first wave of the Covid-19 pandemic) we examine points of tension, manifested at the intersections between community partners, universities and project funders. Extending Strier’s discussion of university-community partnerships (UCP) as ‘fields of paradox’, we outline the complexities of collaborative working within a UCP that seeks to adhere to the priorities of anti-racism and an ethic of love. In doing so this article surfaces the burden of boundary work undertaken by both academic partners seeking to prioritise knowledge and anti-racist practices beyond the academy, and community activists, who are expected to conform with institutional standards that may have little relevance to their practice. The article contributes a series of reflections that may be of use to other activist researchers engaged in UCP.

Joint enterprise (JE) is an extraordinary legal device deployed to punish and (re)produce those who are frequently presented as threatening the normative boundaries of the British state. In acknowledging the global relevance of over-representation and the use of collective punishment, this paper presents the accounts of prisoners who have been convicted under JE laws across England and Wales. Analysis reveals a particular process of criminalisation through police and crown prosecution teams’ construction of the ‘gang’ narrative in courtrooms to drive the disproportionate punishment of members of negatively racialised communities. Of concern, the findings reveal that young Black men in particular are at risk of being convicted and punished for offences they did not commit. This paper empirically demonstrates how such racial injustice originates from a series of targeted and criminalising policies and practices.

BackgroundChikungunya is now of public health concern globally due to its re-emergence in endemic areas and introduction into new areas of the world. Worldwide, the vectors for transmission of the chikungunya virus are Aedes mosquitoes and these are prevalent in Ghana. Despite its global significance, the true burden of chikungunya virus infection in Ghana is largely unknown and the threat of outbreak remains high owing to international travel. This study sought to determine chikungunya virus infection among febrile patients suspected of having malaria infections at some selected health facilities in the Ashanti, Bono East, and Bono Regions of Ghana.MethodologyThis cross-sectional study recruited six hundred (600) febrile patients suspected of having malaria who submitted their clinical samples to the laboratories of the selected health facilities for the diagnosis of their infections. Five to ten millilitres (5-10ml) of venous blood were collected from each study participant. Sera were separated and tested for anti-chikungunya (IgM and IgG) antibodies using InBios ELISA kit following the manufacturer's instruction. Samples positive for chikungunya IgM and IgG were selected and tested for chikungunya virus RNA using Reverse Transcription-quantitative Polymerase Chain Reaction. Malaria Rapid Diagnostic Test kits were used to screen the participants for malaria. Structured questionnaires were administered to obtain demographic and clinical information of the study participants.ResultOf the 600 samples tested, the overall seroprevalence of chikungunya was 6%. The seroprevalence of chikungunya IgM and IgG antibodies were 1.8% and 4.2% respectively. None of the chikungunya IgM and IgG positive samples tested positive for chikungunya RNA by RT-qPCR. Of the 600 samples, tested 32.3% (194/600) were positive for malaria parasites. Malaria and chikungunya co-infection was detected in 1.8% (11/600) of the participants.ConclusionFindings from the current study indicate low-level exposure to the chikungunya virus suggesting the virus is circulating and potentially causing morbidity in Ghana.

Hepatitis B vaccination is the most effective preventive measure in reducing the incidence of chronic hepatitis B virus (HBV) infection and its consequences such as cirrhosis, hepatocellular carcinoma, liver failure and death. Ghana introduced the universal HBV vaccination in the national Expanded Programme on Immunization in 2002. The current study sought to determine the sero-protection rate and the prevalence of HBV infection among fully vaccinated children in the West Gonja District in the Savanna Region of Ghana. This cross-sectional study recruited three hundred and fifty (350) fully vaccinated children who visited West Gonja Catholic Hospital from September to December 2019 for healthcare. Structured questionnaires were administered to obtain information on the demographics. The clinical history of the participants was obtained from the hospital records. Sera were separated from 2-5ml of blood sample collected from each participant after informed consent had been sought from their parents/guardians. Sera were tested for HBsAg, anti-HBs and anti-HBc using ELISA. Samples positive for HBsAg or anti-HBc were tested for HBV DNA by Real-Time Polymerase Chain Reaction. The overall sero-protection rate (anti-HBs titers ≥ 10 mIU/mL) among the studied participants was 56% with anti-HBs geometric mean titer (GMT) of 95.7 mIU/mL (± 6.0; 95% CI) compared with GMT of 2.8 mIU/mL (± 0.2; 95% CI) among non-seroprotected participants. There was no statistically significant difference in sero-protection rate between males and females (p-value = 0.93) and in relation to age (p-value = 0.20). The prevalence of HBV infection among studied participants as determined by the HBV DNA/HBsAg positivity was 1.4% while anti-HBc sero-positivity was 2%. Even though the sero-protection rate and HBV infection rate reported in the current study compares with that of other international studies further studies need to be conducted to understand the factors related to sero-protection and HBV infection rate in the Savanna Region of Ghana.

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Abstract Background Diarrhoeal diseases are among the most frequent causes of morbidity and mortality in children worldwide, especially in sub-Saharan Africa. This case–control study was conducted to investigate the bacterial, viral and parasitic pathogens associated with acute diarrhoea among children attending three health facilities in Kumasi, Ghana. Methods Stool specimens were collected from 240 children under 5 years of age visiting hospitals in Kumasi, Ghana due to acute diarrhoea and from 107 healthy controls of similar age. Both intestinal and malaria parasites were diagnosed by microscopy whereas rota- and adenoviruses were identified by stool antigen immunochromatograhic testing. Bacterial enteropathogens were detected by conventional culture techniques. Results Of all subjects, 23 (6.6%) were positive for malaria parasitaemia, 139 (40.1%) had at least one bacterial agent in their stool and 25 (7.2%) had ova or parasites. Subjects infected with malaria had the highest odds of having diarrhoea [12.0 (95% CI 1.56, 92.35)] followed by those with rotaviruses [4.4 (95% CI 2.05, 9.47)] and bacterial infection [4.99 (95% CI 1.45, 17.17)]. Conclusion In conclusion, this study was unique as it looked at the three groups of pathogens (parasites, viruses and bacteria) that cause acute diarrhoea in children in the Kumasi metropolis of Ghana. This study has shown for the first time since 2004 that malaria parasitaemia, rotavirus and bacterial infections still remain common pathogens associated with acute childhood diarrhoea in the Kumasi metropolis of Ghana.

While participatory culture has been of special interest to scholars for nearly three decades, much of the focus has centered on digitally networked contexts. The digital age has indeed transformed our approaches to listening to music and how we operate as fans of music; these approaches can weave together the new and the old, and are enacted among a variety of spaces, objects, and relationships. We explore how the re-emergence of one such object in the digital age — the LP — has produced social arrangements that perhaps excavate older listening practices but do so in ways that have been affected by the mediascape more generally. We offer the concept of phonography culture: a term that emphasizes the social practices of those who not only curate and collect vinyl records but communicate through them in participatory activities including listening parties, vinyl nights at local bars, Facebook groups, and sites of e-commerce. We share the case study of Record Nite, a semi-regular gathering of phonography culture participants, who take turns playing one side of an LP on a given theme, revealing in their fandom and reveling in and encouraging that of others. Over the course of an evening, ten to twenty friends connect over their own “noise” — their experiences, histories, and knowledge of artists, albums, and genres—while simultaneously listening to LPs together. These phonographic, cultural interactions are revelatory because they draw our attention away from individualized and digital listening, which isolate signal, and make space for social and aural noise. That noise is infused with fandom and participation, as well as elements of memory, meaning making, and nostalgia. NB: The article contains sound examples. In order to listen to embedded audio files, you must first download the pdf file and then open it with Adobe Acrobat.

BackgroundThe study assessed the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection paradigm among the human immunodeficiency virus (HIV) infected patients attending a tertiary hospital in Ghana. Also, the immunological and virological characterisation of these viruses, prior to antiretroviral therapy (ART) initiation was investigated.MethodA total of 400 HIV infected (HIV type-1) treatment naïve subjects ≥18 years were enrolled and tested for HBsAg and anti-HCV. Hepatitis B virus serological profile was performed on samples that were HBV positive. CD4+ T-cell count and HIV-1 RNA viral loads were determined using BD FacsCalibur analyzer (USA) and COBAS AmpliPrep/COBAS TaqMan Analyzer (USA) respectively.ResultsThe overall prevalence of HBV/HCV co-infection among the HIV-1 patients was 18.0%. The prevalence of HIV-HBV and HIV-HCV co-infections were 12.5% and 5.5% respectively. The prevalence of active viral hepatitis (HBeAg-positive) among HIV-HBV co-infected patients was 40%. None of the patients had anti-HBc IgM. HIV-HBV co-infection was associated with lower CD4+ T-cell count as well as higher HIV-1 viral load compared to both HIV mono- infection and HIV-HCV co- infection (pConclusionThe present study highlights the predominance of HBV exposure among the HIV infected patients in Ghana. HBV coinfection was associated with severe immunosuppression and higher HIV-1 viral load.

Introduction: Hip fracture remains the biggest single source of morbidity and mortality in the elderly trauma population, and any intervention focused on quality improvement and system efficiency is beneficial for both patients and clinicians. Two of the variables contributory to improving care and efficiency are time to theater and length of stay, with the overall goal being to improve care as reflected within the achievement of best practice tariff. One of the biggest barriers to optimizing these variables is preinjury anticoagulation. Method: Building on our previous work with warfarin in this population, we utilized a regional hip fracture collaborative network collecting prospective data through the National Hip Fracture Database with custom fields pertaining to all agents, including novel oral anticoagulants. Results: In all, 1965 hip fracture patients median age 83 years (1639 not anticoagulated) were admitted to the 5 centers over 12 months. Median length of stay was 20.71 days; time to theater 23.09 hours, and the populations (anticoagulated vs control) were evenly matched for injury. Anticoagulated patients were delayed to theater ( P ≤ .001), were inpatients for longer ( P ≤ .001) and gained less best practice tariff ( P ≤ .05). All variables per agent were noted and the impact of each assessed. Conclusions: Despite the widespread use of newer anticoagulants, popular due to unmonitored reversal and administration, patients stay longer in hospital and wait longer for surgery than nonanticoagulated patients of the same age and injury. Contemporary perioperative practices impact negatively on the ability to perform timely surgery on hip fracture patients. We propose a guideline specific to the management of anticoagulation in the hip fracture population to aid the optimum preparation of patients for theater, achievement of timely surgery, and potentially reduce length of stay.

To all Gypsy groups the factum is common, that they are firmly enclosed by a society, from whichthey want to keep distance. Analyzing the relations between this communities and the larger societymeets tendencies of amalgamating as well as tendencies of separating. Among the latter the originalityand creativity in putting together the ‘own culture’ are striking, so that a permanent significatof distance (Gypsy identity) is opposed to flexible significants of distancing (cultural traits), whichare often transformed elements of the majority culture.

Durante los inicios del reinado de Felipe III maduró la nueva cultura cortesana española. Los fastos celebrados en la corte de Valladolid con motivo del nacimiento de Felipe IV dieron ocasión a Lerma para exhibir su enorme poder estableciendo para toda su generación el modelo de cortesano que era al mismo tiempo ministro, esteta y soldado. De esta eclosión cortesana fueron testigos de excepción los componentes de la delegación inglesa que había viajado a Valladolid para ratificar la Paz de Londres de 1604 firmada un año antes. Los ingleses regresaron con la imagen de una corte joven, refinada y llena de entusiasmo cuyo impacto estaba destinado a sentirse en toda Europa.

Throughout this paper, we contend that the ‘gang’ has been appropriated by the state as an ideological device that drives the hypercriminalisation of black, mixed, Asian, and other minority ethnic (BAME) communities. Drawing upon two research studies, we demonstrate how the gang is evoked to explain an array of contemporary ‘crime’ problems, which in turn (re)produces racialised objects to be policed. With particular reference to collective punishments, we suggest that “gang-branding„ is critical to the development of guilt-producing associations that facilitate the arrest, charging, and prosecution of countless numbers of BAME people for offences they did not commit. As such, there is now an urgent need to ‘take seriously’ the criminalising intents of a dangerous criminology of the Other, which legitimises intrusive racist policing and surveillance, and justifies the imposition of deliberate harms upon racialised communities.

David Callanan, Patrick WilliamsTexas Retina Associates, Arlington, TX, USAPurpose: To determine the safety and efficacy of topical nepafenac 0.1% in the treatment of diabetic macular edema.Methods: A consecutive case series was performed of patients treated with nepafenac monotherapy twice daily for diabetic macular edema. Visual acuities (VA) at baseline and final visit were recorded. Foveal thickness, based on optical coherence tomography, was also recorded.Results: Six eyes of 5 patients were included in this study. Median initial Snellen vision was 20/100 (range, 20/40–20/400). After a mean of 210 days (range, 182–259), median final VA was 20/75 (range, 20/40–20/400). Four eyes gained vision and two eyes maintained vision. Mean pre-treatment vision was 0.78 logMAR and final VA was 0.67 logMAR, for a statistically significant improvement (p < 0.05). Mean initial foveal thickness was 417 microns (range, 286–599). After a mean of 178 days (range, 91–259), mean foveal thickness was 267 microns (range, 158–423), showing a statistically significant improvement (p < 0.05). Each eye had an improvement in foveal thickness.Conclusion: The results from these 6 eyes suggest that nepafenac 0.1% may have activity against diabetic macular edema and warrants further investigation.Keywords: diabetes, diabetic macular edema, inflammation, macular edema, nepafenac, NSAIDs