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Adonis El Salloukh,1,* Murad Khan,2,* Patrick Watts,1 Phillip M Newton,3 Gwyn Samuel Williams4 1Ophthalmology Department, University Hospital of Wales, Cardiff, Wales, UK; 2Birmingham and Midlands Eye Centre, Birmingham, England, UK; 3Neuroscience and Medical Education, Swansea University, Wales, UK; 4Ophthalmology Department, Singleton Hospital, Swansea, Wales, UK*These authors contributed equally to this workCorrespondence: Murad Khan, Birmingham and Midlands Eye Centre, City Hospital, Dudley Road, Birmingham, B18 7QH, UK, Email muradatherkhan@gmail.comPurpose: Mental workload is a recognised concept in medicine, and cognitive overload may lead to complications in surgery, including cataract surgery. A better understanding of what factors contribute to this can potentially improve patient safety and decrease surgeon stress. Simulated cataract surgery is now an essential part of training and a safe environment for exploring the effects of cognitive load upon performance. We used the EyeSi cataract surgery simulator to assess the effects of distraction on surgical performance and on ophthalmology trainees and consultants undertaking cataract surgery.Patients and Methods: Consultant and trainee cataract surgeons undertook a simulated list of six cases each, of which half were allowed to proceed without extraneous cognitive load with distraction and half were not. Blood pressure and pulse measurements were taken at three intervals in each of the six cases, as well as surgical scores on the simulator recorded for each case.Results: Distraction did not statistically significantly affect the scores, blood pressure or pulse measurements of either the 10 trainees or 10 consultants. Consultants performed more poorly than trainees overall (P = 0.0229) and suffered more serious errors that returned a score of zero for an individual stage (P = 0.0074).Conclusion: Consultant cataract surgeons performed worse than trainees on the EyeSi simulator, raising questions over whether simulation is as true to reality as has been suggested. An important finding is that ophthalmic training curricula around the world have been adapted in order to include simulated cataract surgery as an essential component of training new ophthalmic surgeons.Keywords: simulation, cataract surgery, ophthalmology

Francis WB Sanders,1 Rebecca John,2 Philip Jones,3 Gwyn Samuel Williams1 1Department of Ophthalmology, Singleton Hospital, Swansea, UK; 2Primary Care Services, NHS Wales Shared Services Partnership, Cardiff, UK; 3Optometry Division, Specsavers Opticians, Swansea, UKCorrespondence: Rebecca John, Email Rebecca.john20@wales.nhs.ukBackground: The prevalence of neovascular age-related macular degeneration (nAMD) continues to increase. Hospital Eye Services are operating above capacity, innovative solutions to minimise the high proportion of false negative referrals, improve the care pathway and increase capacity for those patients who need ongoing care are essential are essential.Methods: A two-phase retrospective longitudinal analysis of all patients referred and assessed for nAMD between; April 2019 to March 2020 (Phase 1) n=394, and April 2020 to March 2021 (Phase 2) n= 414, within Swansea Bay University Health Board (SBUHB). All patients with suspect nAMD were referred to the hospital based nAMD clinic in phase 1, and a community optometry nAMD decision making pathway in phase 2. All clinical records were reviewed, and data collated for subsequent analysis. Age, sex, date of referral, diagnosis, and treatment date were all recorded and analysed.Results: During phase 1, 104 new nAMD cases needing treatment were diagnosed with 85% (n=88) receiving treatment within 2 weeks of initial referral. During phase 2, 230 new nAMD cases requiring treatment were diagnosed with 94% (n=216) receiving treatment within 2 weeks of initial referral. Both the proportion of nAMD cases diagnosed (χ² = 70.8; p< 0.001) and proportion of those treated within 2 weeks of initial diagnosis (χ² = 7.57; p< 0.05) were significantly higher during phase 2.Conclusion: There are advantages to a community optometry nAMD decision-making pathway with regard to 1) decreasing the number of patients requiring HES attendance, 2) increasing the number of patients able to access treatment for nAMD within 2 weeks of initial referral 3) an increased rate of diagnosis confirmation of nAMD and 4) a decrease in the rate of false-positive referrals.Keywords: age-related-macular-degeneration, primary care, shared care, public health

Danielle Modeste,1 Christopher Stewart,2 Hajani Premanandhan,2 Mahmoud Husseiny Awad,1 Gwyn Samuel Williams1 1Ophthalmology, Singleton Hospital, Swansea Bay University Health Board, Swansea, Wales, UK; 2Swansea Bay University, Medical School, Swansea, Wales, UKCorrespondence: Danielle Modeste, Ophthalmology Department, Singleton Hospital Sketty Ln, Sketty, Swansea, UK, SA2 8QA, Email danielle.modeste@wales.nhs.ukPurpose: To evaluate the efficiency and safety of Faricimab on treatment-naive neovascular age related macular degeneration (nAMD) in a real world UK clinic.Patients and Methods: This single centre, retrospective note review was conducted on treatment-naive patients with nAMD. The data collected included demographics, best corrected visual acuity (BCVA), central macular thickness (CMT), total retinal fluid (TRF), the presence of intraretinal fluid (IRF) and subretinal fluid (SRF).Results: A total of 66 eyes from 62 patients were analysed. The average age was 77 years (range 36– 91) and 54% of patients were female. After the first dose of faricimab, the average BCVA improved by 0.05 LogMAR (+2.5 letters), the average CMT decreased by 65.9μm and 41% of patients were found to be inactive. The follow-up intervals after the third loading dose were divided into 2 subsets of 4 and 8 week extensions. The 4 week extension subset saw a smaller improvement in BCVA (+3 letters) than the 8 week extension (+6 letters) while both had an average decrease in CMT by 86.6 μm. The total retinal fluid decreased by 45% and 70.7%, leaving only 30% and 12.2% residual intraretinal fluid (IRF) and 30% and 24.4% residual subretinal fluid (SRF), respectively. Over a ten-month period, the average number of injections received was 6.6, including 3 initial loading doses. There was only one reported case of an adverse event out of 66 eyes (1/66, 1.5%).Conclusion: Three loading doses of Faricimab appear efficacious and safe for the treatment of nAMD.Plain language Summary: What is already known on this topic:Faricimab is recombinant humanised bispecific IgG monoclonal antibody which binds and neutralises both VEGF-A and angiopoietin-2 (VEGFA and ANG2).Clinical trials have reported faricimab dosing intervals of up to Q16W.What this study adds:To offer a glimpse into real-world effectiveness and safety of faricimab beyond the constraints of a randomised controlled study in treatment naïve nAMD patients.Presents results derived from implementing a “Treat and Extend” algorithm with faricimab in nAMD management, showcasing its beneficial impact on the strategic planning and execution of patient care.How this research may affect research, practice or policy:Faricimab should be seen as a viable therapy in treatment-naive patients with nAMD.Employing a shortened loading regimen of three doses presents no discernible detriment to treatment efficacy when compared to the established four-dose schedule.Keywords: treatment-naïve, nAMD, Faricimab, dosing interval

Francis WB Sanders, Rhys Dumont Jones, David R Jones, Sean V Phillips, Gwyn S Williams Department of Ophthalmology, Singleton Hospital, Swansea, UKCorrespondence: Francis WB Sanders, Department of Ophthalmology, Singleton Hospital, Sketty Lane, Sketty, Swansea, SA2 8QA, United Kingdom, Tel +44 1792 205666, Email francis.sanders@wales.nhs.ukPurpose: To assess the “real world” utility of repeated injection with the dexamethasone intravitreal implant (DEX) in routine practice.Methods: This was a retrospective, single-center analysis of consecutive patients with diabetic macular edema, or macular edema following retinal vein occlusion, treated with DEX. None had received prior intravitreal steroid treatment. DEX was implanted as per the manufacturer’s instructions.Results: Seventy-eight individuals (95 eyes) were included (50.0% female; mean age: 68.1 ± 12.4 years; mean duration of macular edema: 13.2 ± 12.9 months). Thirty-three eyes (34.7%) had received previous treatment with an anti-vascular endothelial growth factor (anti-VEGF) and/or laser. Thirty eyes (31.6%) underwent one round of DEX implantation; the remainder received 2– 5 cycles (total: 225 cycles). Initial DEX treatment led to significant increases in visual acuity (VA) at 6 weeks (mean change: 4.6 letters; P=0.004). Greater VA improvements during the first treatment cycle were associated with inferior baseline VA (P=0.02), borderline associated with baseline central macular thickness (CMT; P=0.06), and independent of prior anti-VEGF treatment (P=0.39). In an analysis of all DEX injections, VA improvements were robust across cycles 1 and 2 but reduced in cycle 3 (P=0.03). CMT improvements did not differ based on injection number (P=0.20). Increases in intraocular pressure (IOP) were largest over the first 6 weeks (but rebounded towards baseline more rapidly) in cycle 1 versus cycles 2 and 3 (P< 0.001). IOP rises were typically manageable with topical medications.Conclusion: This analysis confirms the broad utility of DEX and may inform decision-making in routine practice.Keywords: corticosteroid, dexamethasone intravitreal implant, diabetic macular edema, intraocular pressure, retinal vein occlusion, visual acuity

We have generated a second line of mice lacking a transcription factor thought to be a critical regulator of MHC class II gene expression, CIITA (for class II transactivator). Our and the previously published lines differ in the deletion that was engineered and by the fact that we removed the neomycin-resistance promoter and structural gene via the cre-loxP recombination system. Characterization of our line led to two new findings. First, a substantial number of cells can express class II molecules in the absence of CIITA, albeit of 5-fold reduced levels, most notably dendritic cells in s.c. lymph nodes; therefore, the CIITA gene cannot be an absolute 'master gene' controlling the expression of class II molecules, as had been thought. Second, in contrast to recent results on human cell lines, CIITA is not critically involved in the IFN-γ-induced up-regulation of MHC class I genes. [ABSTRACT FROM PUBLISHER]

OBJECTIVE: To determine the personal attributes and job competencies that are necessary for the job success of Expanded Food and Nutrition Education Program (EFNEP) paraprofessionals as perceived by EFNEP professionals. DESIGN: A qualitative descriptive design and a 3-round modified Delphi methodology was used. PARTICIPANTS: A convenience sample of 14 state and 20 county EFNEP professionals participated in all 3 Delphi rounds. The response rates for state and county professionals for all 3 Delphi rounds were 70% and 91%, respectively. VARIABLES MEASURED: Personal attributes and job competencies were generated and the level of importance was determined. Analysis: An independent t test was employed to determine differences between importance scores by professional position. RESULTS: Thirty-seven personal attributes, 18 job competencies prior to hire, and 43 job competencies after training were generated and the majority were very important to important. County EFNEP professionals tended to score personal attributes and job competencies as more important than state EFNEP professionals. IMPLICATIONS: These personal attributes and job competencies prior to hire can guide hiring decisions and initial training content. The job competencies after training can shape content for inservice training. [ABSTRACT FROM AUTHOR]

WHO works, on a daily basis, with countries globally to detect, prepare for and respond to acute public health events. A vital component of a health response is the dissemination of accurate, reliable and authoritative information. The Disease Outbreak News (DON) reports are a key mechanism through which WHO communicates on acute public health events to the public. The decision to produce a DON report is taken on a case-by-case basis after evaluating key criteria, and the subsequent process of producing a DON report is highly standardised to ensure the robustness of information. DON reports have been published since 1996, and up to 2022 over 3000 reports have been published. Between 2018 and 2022, the most frequently published DON reports relate to Ebola virus disease, Middle East respiratory syndrome, yellow fever, polio and cholera. The DON web page is highly visited with a readership of over 2.6 million visits per year, on average. The DON report structure has evolved over time, from a single paragraph in 1996 to a detailed report with seven sections currently. WHO regularly reviews the DON report process and structure for improvements. In the last 25 years, DON reports have played a unique role in rapidly disseminating information on acute public health events to health actors and the public globally. They have become a key information source for the global public health response to the benefit of individuals and communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

In vitro preclinical drug-induced liver injury (DILI) risk assessment relies largely on the use of hepatocytes to measure drug-specific changes in cell function or viability. Unfortunately, this does not provide indications toward the immunogenicity of drugs and/or the likelihood of idiosyncratic reactions in the clinic. This is because the molecular initiating event in immune DILI is an interaction of the drug-derived antigen with MHC proteins and the T-cell receptor. This study utilized immune cells from drug-naïve donors, recently established immune cell coculture systems and blinded compounds with and without DILI liabilities to determine whether these new methods offer an improvement over established assessment methods for the prediction of immune-mediated DILI. Ten blinded test compounds (6 with known DILI liabilities; 4 with lower DILI liabilities) and 5 training compounds, with known T-cell-mediated immune reactions in patients, were investigated. Naïve T-cells were activated with 4/5 of the training compounds (nitroso sulfamethoxazole, vancomycin, Bandrowski's base, and carbamazepine) and clones derived from the priming assays were activated with drug in a dose-dependent manner. The test compounds with DILI liabilities did not stimulate T-cell proliferative responses during dendritic cell-T-cell coculture; however, CD4+ clones displaying reactivity were detected toward 2 compounds (ciprofloxacin and erythromycin) with known liabilities. Drug-responsive T-cells were not detected with the compounds with lower DILI liabilities. This study provides compelling evidence that assessment of intrinsic drug immunogenicity, although complex, can provide valuable information regarding immune liabilities of some compounds prior to clinical studies or when immune reactions are observed in patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology.)

Introduction: For end-stage renal disease (ESRD) patients residing in skilled nursing facilities (SNFs), the logistics and physical exhaustion of life-saving hemodialysis therapy often conflict with rehabilitation goals. Integration of dialysis care with rehabilitation programs in a scalable and cost-efficient manner has been a significant challenge. SNF-resident ESRD patients receiving onsite, more frequent hemodialysis (MFD) have reported rapid post-dialysis recovery. We examined whether such patients have improved Physical Therapy (PT) participation., Methods: We conducted a retrospective electronic medical records review of SNF-resident PT participation rates within a multistate provider of SNF rehabilitation care from January 1, 2022 to June 1, 2022. We compared three groups: ESRD patients receiving onsite MFD (Onsite-MFD), ESRD patients receiving offsite, conventional 3×/week dialysis (Offsite-Conventional-HD), and the general non-ESRD SNF rehabilitation population (Non-ESRD). We evaluated physical therapy participation rates based on a predefined metric of missed or shortened (<15 min) therapy days. Baseline demographics and functional status were assessed., Findings: Ninety-two Onsite-MFD had 2084 PT sessions scheduled, 12,916 Non-ESRD had 225,496 PT sessions scheduled, and 562 Offsite-Conventional-HD had 9082 PT sessions scheduled. In mixed model logistic regression, Onsite-MFD achieved higher PT participation rates than Offsite-Conventional-HD (odds ratio: 1.8, CI: 1.1-3.0; p < 0.03), and Onsite-MFD achieved equivalent PT participation rates to Non-ESRD (odds ratio: 1.2, CI: 0.3-1.9; p < 0.46). Baseline mean ± SD Charlson Comorbidity score was significantly higher in Onsite-MFD (4.9 ± 2.0) and Offsite-Conventional-HD (4.9 ± 1.8) versus Non-ESRD (2.6 ± 2.0; p < 0.001). Baseline mean self-care and mobility scores were significantly lower in Onsite-MFD versus Non-ESRD or Offsite-Conventional-HD., Discussion: SNF-resident ESRD patients receiving MFD colocated with rehabilitation had higher PT participation rates than those conventionally dialyzed offsite and equivalent PT participation rates to the non-ESRD SNF-rehabilitation general population, despite being sicker, less independent, and less mobile. We report a scalable program integrating dialysis and rehabilitation care as a potential solution for ESRD patients recovering from acute hospitalization., (© 2023 The Authors. Hemodialysis International published by Wiley Periodicals LLC on behalf of International Society for Hemodialysis.)

The African Region reports the heaviest burden of public health emergencies globally. This paper presents an exploratory analysis of public health events data collected the past 22 years in the WHO Africa region, to explore patterns and trends that can inform public health strategies, policy changes and develop appropriate tools to improve disease surveillance, preparedness and response to public health emergencies. A suite of exploratory data analysis methods combining time series analysis, summary statistics, temporal visualisations, geographic information system (GIS) mapping, trend analysis and statistical tests were used to derive patterns and trends from the data. An in-depth analysis of zoonotic disease outbreaks by geography and time was explored. The analysis also focused on whether these outbreaks were viral haemorrhagic related or had other characteristics. Results reveal that between 2001 and 2022, a total of 2234 public health events have been recorded in the WHO African Region of which 1886 events (84.4%) were substantiated. The paper confirms an average of 102 public health events reported yearly during the last 22 years time frame. The large majority (92%) of the substantiated events were infectious diseases (n=1730), 30% (n=566) are zoonoses and 5% (n=95) are humanitarian crises such as disaster events and conflicts. The number of zoonotic disease outbreaks has significantly increased (by 87%) between the past two decades, from 2003 to 2012 period (M=18.6, SD=4.8) and 2013-2022 period (M=34.7, SD=14); t(18) = 3.4, p=0.0032. This analysis shows growing challenges faced in the Africa region every year. One-health approach and its coordination across multiple sectors, disciplines and communities is critical to achieve the objectives., Competing Interests: Competing interests: None declared., (© World Health Organization 2023. Licensee BMJ.)

Background: In May 2022, several countries with no history of sustained community transmission of mpox (formerly known as monkeypox) notified WHO of new mpox cases. These cases were soon followed by a large-scale outbreak, which unfolded across the world, driven by local, in-country transmission within previously unaffected countries. On July 23, 2022, WHO declared the outbreak a Public Health Emergency of International Concern. Here, we aim to describe the main epidemiological features of this outbreak, the largest reported to date., Methods: In this analysis of global surveillance data we analysed data for all confirmed mpox cases reported by WHO Member States through the global surveillance system from Jan 1, 2022, to Jan 29, 2023. Data included daily aggregated numbers of mpox cases by country and a case reporting form (CRF) containing information on demographics, clinical presentation, epidemiological exposure factors, and laboratory testing. We used the data to (1) describe the key epidemiological and clinical features of cases; (2) analyse risk factors for hospitalisation (by multivariable mixed-effects binary logistic regression); and (3) retrospectively analyse transmission trends. Sequencing data from GISAID and GenBank were used to analyse monkeypox virus (MPXV) genetic diversity., Findings: Data from 82 807 cases with submitted CRFs were included in the analysis. Cases were primarily due to clade IIb MPXV (mainly lineage B.1, followed by lineage A.2). The outbreak was driven by transmission among males (73 560 [96·4%] of 76 293 cases) who self-identify as men who have sex with men (25 938 [86·9%] of 29 854 cases). The most common reported route of transmission was sexual contact (14 941 [68·7%] of 21 749). 3927 (7·3%) of 54 117 cases were hospitalised, with increased odds for those aged younger than 5 years (adjusted odds ratio 2·12 [95% CI 1·32-3·40], p=0·0020), aged 65 years and older (1·54 [1·05-2·25], p=0·026), female cases (1·61 [1·35-1·91], p<0·0001), and for cases who are immunosuppressed either due to being HIV positive and immunosuppressed (2·00 [1·68-2·37], p<0·0001), or other immunocompromising conditions (3·47 [1·84-6·54], p=0·0001)., Interpretation: Continued global surveillance allowed WHO to monitor the epidemic, identify risk factors, and inform the public health response. The outbreak can be attributed to clade IIb MPXV spread by newly described modes of transmission., Funding: WHO Contingency Fund for Emergencies., Translations: For the French and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interest., (This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: We aimed to evaluate the nationwide prevalence of stress induced burnout among cataract surgeons. We believe that knowledge of these factors can help formulate a solution to this underreported problem., Methods: A three-part nationwide cross-sectional survey was disseminated with via the Royal College of Ophthalmologists (RCOphth) in the United Kingdom(UK). All consultants, trainees and specialty doctors and associate specialists(SAS) were invited to participate. We evaluated burnout using the Maslach Burnout Inventory (MBI). Logistic regression modelling was completed to look at factors linked to high level burnout in certain domains., Results: A total of 406 respondents completed our survey. Prevalence of cataract surgery-related high burnout was estimated at 3.45% (Section A and/or B) and 40% within Personal Accomplishment (PA)(Section C of the MBI). Multiple factors were associated with increased burnout within PA: Increasing age: 61+ OR: 2.99 (1.02-8.78, p  =   0.05), Number of cataract operations completed: >3000 OR 2.98 (1.03-8.64, p  =   0.04), Lists per week: 2: OR 2.99 (1.38-6.47, p  <   0.01), 2.5: OR 8.95 (2.58-31.02, p  <   0.01), 3 or more: OR 2.64 (1.07-6.54, p  =   0.04). Sleeping 8 h or more was found to be protective OR 0.52 (0.28-0.96, p  =   0.04). 17% of respondents indicated they would be willing to give up cataract surgery if given the opportunity., Conclusion: The prevalence of stress induced burnout by cataract surgery appears to be present in a minority of surgeons. There appears to be a significant reduction in the feeling of personal achievement within the profession. A large proportion of this cohort appears to be willing to give up surgical responsibilities.

Lymphocytes are usually interpreted as functioning in adaptive immunity despite evidence that large proportions of these cells (B1 lymphocytes) have innate immune functions, including phagocytosis, in the peripheral blood of ectothermic vertebrates. We used a recently optimized assay to assess environmental influences on phagocytic activity of lymphocytes isolated from the Mojave desert tortoise (Gopherus agassizii). Previous studies suggest that lymphocytes in this species are associated with reduced pathogen loads, especially in cooler climates, and that lymphocyte numbers fluctuate seasonally. Thus, we evaluated thermal dependence of phagocytic activity in vitro and across seasons. While B1 lymphocytes appeared to be cold-adapted and always increased phagocytosis at cool temperatures, we also found evidence of thermal acclimation. Tortoises upregulated these lymphocytes during cooler seasons in the fall as their preferred body temperatures dropped, and phagocytosis also increased in efficiency during this same time. Like many other ectothermic species, populations of desert tortoises are in decline, in part due to a cold-adapted pathogen that causes chronic respiratory disease. Future studies, similarly focused on the function of B1 lymphocytes, could serve to uncover new patterns in thermal acclimation of immune functions and disease ecology across taxa of ectothermic vertebrates., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

The geographic and economic characteristics unique to island nations create a different set of conditions for, and responses to, the spread of a pandemic compared with those of mainland countries. Here, we aimed to describe the initial period of the COVID-19 pandemic, along with the potential conditions and responses affecting variation in the burden of infections and severe disease burden, across the six island nations of the WHO's Africa region: Cabo Verde, Comoros, Madagascar, Mauritius, São Tomé e Príncipe and Seychelles. We analysed the publicly available COVID-19 data on confirmed cases and deaths from the beginning of the pandemic through 29 November 2020. To understand variation in the course of the pandemic in these nations, we explored differences in their economic statuses, healthcare expenditures and facilities, age and sex distributions, leading health risk factors, densities of the overall and urban populations and the main industries in these countries. We also reviewed the non-pharmaceutical response measures implemented nationally. We found that the burden of SARS-CoV-2 infection was reduced by strict early limitations on movement and biased towards nations where detection capacity was higher, while the burden of severe COVID-19 was skewed towards countries that invested less in healthcare and those that had older populations and greater prevalence of key underlying health risk factors. These findings highlight the need for Africa's island nations to invest more in healthcare and in local testing capacity to reduce the need for reliance on border closures that have dire consequences for their economies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

As of 03 January 2021, the WHO African region is the least affected by the coronavirus disease-2019 (COVID-19) pandemic, accounting for only 2.4% of cases and deaths reported globally. However, concerns abound about whether the number of cases and deaths reported from the region reflect the true burden of the disease and how the monitoring of the pandemic trajectory can inform response measures.We retrospectively estimated four key epidemiological parameters (the total number of cases, the number of missed cases, the detection rate and the cumulative incidence) using the COVID-19 prevalence calculator tool developed by Resolve to Save Lives. We used cumulative cases and deaths reported during the period 25 February to 31 December 2020 for each WHO Member State in the region as well as population data to estimate the four parameters of interest. The estimated number of confirmed cases in 42 countries out of 47 of the WHO African region included in this study was 13 947 631 [95% confidence interval (CI): 13 334 620-14 635 502] against 1 889 512 cases reported, representing 13.5% of overall detection rate (range: 4.2% in Chad, 43.9% in Guinea). The cumulative incidence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was estimated at 1.38% (95% CI: 1.31%-1.44%), with South Africa the highest [14.5% (95% CI: 13.9%-15.2%)] and Mauritius [0.1% (95% CI: 0.099%-0.11%)] the lowest. The low detection rate found in most countries of the WHO African region suggests the need to strengthen SARS-CoV-2 testing capacities and adjusting testing strategies.

Experience gained from responding to major outbreaks may have influenced the early coronavirus disease-2019 (COVID-19) pandemic response in several countries across Africa. We retrospectively assessed whether Guinea, Liberia and Sierra Leone, the three West African countries at the epicentre of the 2014-2016 Ebola virus disease outbreak, leveraged the lessons learned in responding to COVID-19 following the World Health Organization's (WHO) declaration of a public health emergency of international concern (PHEIC). We found relatively lower incidence rates across the three countries compared to many parts of the globe. Time to case reporting and laboratory confirmation also varied, with Guinea and Liberia reporting significant delays compared to Sierra Leone. Most of the selected readiness measures were instituted before confirmation of the first case and response measures were initiated rapidly after the outbreak confirmation. We conclude that the rapid readiness and response measures instituted by the three countries can be attributed to their lessons learned from the devastating Ebola outbreak, although persistent health systems weaknesses and the unique nature of COVID-19 continue to challenge control efforts.

This study analysed the reported incidence of COVID-19 and associated epidemiological and socio-economic factors in the WHO African region. Data from COVID-19 confirmed cases and SARS-CoV-2 tests reported to the WHO by Member States between 25 February and 31 December 2020 and publicly available health and socio-economic data were analysed using univariate and multivariate binomial regression models. The overall cumulative incidence was 1846 cases per million population. Cape Verde (21 350 per million), South Africa (18 060 per million), Namibia (9840 per million), Eswatini (8151 per million) and Botswana (6044 per million) recorded the highest cumulative incidence, while Benin (260 per million), Democratic Republic of Congo (203 per million), Niger (141 cases per million), Chad (133 per million) and Burundi (62 per million) recorded the lowest. Increasing percentage of urban population (β = -0.011, P = 0.04) was associated with low cumulative incidence, while increasing number of cumulative SARS-CoV-2 tests performed per 10 000 population (β = 0.0006, P = 0.006) and the proportion of population aged 15-64 years (adjusted β = 0.174, P < 0.0001) were associated with high COVID-19 cumulative incidence. With limited testing capacities and overwhelmed health systems, these findings highlight the need for countries to increase and decentralise testing capacities and adjust testing strategies to target most at-risk populations.

Purpose: Cataract extraction and lens implantation is the most common surgical procedure performed worldwide, with surgeons opting for either a topical or a subtenon anesthetic in majority of cases. While complication rates and pain scores have been previously examined in a bid to determine which modality was better, patients who have had both eyes operated upon under different techniques have never previously been asked which method they prefer. We undertook this study to fill in this crucial gap in our knowledge., Methods: This is a retrospective study of patients who have undergone bilateral cataract surgery with one eye operated on with topical anesthesia and the other eye with subtenon anesthesia. Patients were identified who had had surgery undertaken in the previous 6 months at Singleton Hospital, Swansea, where both eyes had been operated upon using different anesthetic techniques. Telephone interviews with these patients were performed and their pain scores recorded on a scale from 0 (no pain) to 10 (severe pain) for both eyes, with the patients then being asked which the method of anesthetic they preferred. Statistical analysis of pain scores was compared using Wilcoxon rank-sum testing., Results: One hundred and fifty-two patients in total were identified. One hundred and forty-one of the applicable patients participated in the study. Of these, 78 patients received topical anesthesia for their first operation and 63 had subtenon block for their first operation. The mean pain scores reported for surgery with topical anesthesia and subtenon block were 2.30 and 1.38, respectively. The pain data were analyzed using a Wilcoxon signed-rank test, returning a z-score of 4.038. This result therefore suggests that patients experience statistically significantly less pain from cataract surgery when given a subtenon block. Patients expressed a preference for subtenon anesthesia, with 70% preferring subtenon block, 23% preferring topical anesthesia, and 7% having no preference., Conclusions: Patients report less pain with subtenon anesthesia compared with topical anesthesia in cataract surgery, where both eyes were operated upon with different anesthetic techniques. This is the first study in which patients who have had both anesthetic techniques performed independently for cataract surgery have had their pain scores reported and statistically analyzed., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Saudi Journal of Ophthalmology.)

Epidemic intelligence activities are undertaken by the WHO Regional Office for Africa to support member states in early detection and response to outbreaks to prevent the international spread of diseases. We reviewed epidemic intelligence activities conducted by the organisation from 2017 to 2020, processes used, key results and how lessons learned can be used to strengthen preparedness, early detection and rapid response to outbreaks that may constitute a public health event of international concern. A total of 415 outbreaks were detected and notified to WHO, using both indicator-based and event-based surveillance. Media monitoring contributed to the initial detection of a quarter of all events reported. The most frequent outbreaks detected were vaccine-preventable diseases, followed by food-and-water-borne diseases, vector-borne diseases and viral haemorrhagic fevers. Rapid risk assessments generated evidence and provided the basis for WHO to trigger operational processes to provide rapid support to member states to respond to outbreaks with a potential for international spread. This is crucial in assisting member states in their obligations under the International Health Regulations (IHR) (2005). Member states in the region require scaled-up support, particularly in preventing recurrent outbreaks of infectious diseases and enhancing their event-based surveillance capacities with automated tools and processes.

Successive waves of COVID-19 transmission have led to exponential increases in new infections globally. In this study, we have applied a decision-making tool to assess the risk of continuing transmission to inform decisions on tailored public health and social measures (PHSM) using data on cases and deaths reported by Member States to the WHO Regional Office for Africa as of 31 December 2020. Transmission classification and health system capacity were used to assess the risk level of each country to guide implementation and adjustments to PHSM. Two countries out of 46 assessed met the criteria for sporadic transmission, one for clusters of cases, and 43 (93.5%) for community transmission (CT) including three with uncontrolled disease incidence (Eswatini, Namibia and South Africa). Health system response's capacities were assessed as adequate in two countries (4.3%), moderate in 13 countries (28.3%) and limited in 31 countries (64.4%). The risk level, calculated as a combination of transmission classification and health system response's capacities, was assessed at level 0 in one country (2.1%), level 1 in two countries (4.3%), level 2 in 11 countries (23.9%) and level 3 in 32 (69.6%) countries. The scale of severity ranged from 0 to 4, with 0 the lowest. CT coupled with limited response capacity resulted in a level 3 risk assessment in most countries. Countries at level 3 should be considered as priority focus for additional assistance, in order to prevent the risk rising to level 4, which may necessitate enforcing hard and costly lockdown measures. The large number of countries at level 3 indicates the need for an effective risk management system to be used as a basis for adjusting PHSM at national and sub-national levels.

Introduction: Treatment of juvenile idiopathic arthritis (JIA)-associated uveitis necessitates the use of long-term corticosteroids or immunosuppressive agents, each of which poses their own significant side effect profile. Initial treatment requires intensive topical glucocorticoids, with a step-up approach employing immunosuppressive agents for those cases with poor response or high-risk complications such as macular oedema. To date, there is minimal evidence to support a specific approach to such complicated subgroups. We present the first case to successfully employ the 0.19 mg fluocinolone acetonide implant (ILUVIEN ® , Alimera Sciences, Hampshire, UK) as a novel device for prolonged intravitreal administration of disease-modifying agents for patients with JIA complicated by uveitis., Methods: This retrospective case report describes a 20-year old woman diagnosed with oligoarticular JIA complicated by chronic uveitis and associated cystoid macular oedema (CMO). Considering factors including the patient's non-compliance, age, lens status, non-steroid response, and good response to short-term intravitreal steroid therapy, the 0.19 mg fluocinolone acetonide intravitreal implant was deemed an appropriate step-up treatment option., Results: At 12-month follow-up, the left eye (OS) showed an improvement in visual acuity to 6/15 - 1 from 6/60 + 1 (0.42 from 0.98 logMAR) (pre-insertion) and a reduction in central retinal thickness (CRT) of 199 μm from 471 μm. The right eye (OD), treated 10 months later, showed an improvement in visual acuity to 6/7.5 from 6/24 - 1 (0.10 from 0.56 LogMAR) and a reduction in CRT of 327 μm 6 months after treatment., Conclusion: In this case, the 0.19 mg fluocinolone acetonide implant provided safe and effective long-term treatment of JIA-associated uveitis and secondary CMO. This potentially offers an alternative approach to complex cases that show good response to short-term corticosteroid use.

Large-scale protracted outbreaks can be prevented through early detection, notification, and rapid control. We assessed trends in timeliness of detecting and responding to outbreaks in the African Region reported to the World Health Organization during 2017-2019. We computed the median time to each outbreak milestone and assessed the rates of change over time using univariable and multivariable Cox proportional hazard regression analyses. We selected 296 outbreaks from 348 public reported health events and evaluated 184 for time to detection, 232 for time to notification, and 201 for time to end. Time to detection and end decreased over time, whereas time to notification increased. Multiple factors can account for these findings, including scaling up support to member states after the World Health Organization established its Health Emergencies Programme and support given to countries from donors and partners to strengthen their core capacities for meeting International Health Regulations.

We report a very unusual presentation of primary intraocular lymphoma masquerading as anterior uveitis with atypical symptoms. A 68-year-old man, initially presented with a 4-day history of painless, left blurred vision. Examination revealed 2 or more anterior chamber cells, mutton-fat keratic precipitates and posterior synechiae. Treatment was initiated, the eye settled, and the patient was discharged. He re-presented 7 months later with hypopyon, a hazy cornea, fibrin deposits and a narrowed anterior chamber angle. Over the coming weeks, it became apparent that the temporal iris was thickened, involving the angle, and his intraocular pressure increased despite topical dorzolamide. Following advice from a tertiary centre and referral to a regional ocular oncology centre, a transscleral biopsy was performed and suggested a ciliary body melanoma. Enucleation was advised and performed, with histological examination revealing features consistent with an ocular diffuse large B-cell lymphoma not involving the optic nerve, sclera or cornea. This is the first ever published report of a case of ocular lymphoma masquerading in this way., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Measles is an acute viral disease that remains endemic in much of sub-Sahara Africa, including Liberia. The 2014 Ebola epidemic disrupted an already fragile health system contributing to low uptake of immunization services, population immunity remained low thus facilitating recurrent outbreaks of measles in Liberia. We describe lessons learnt from detecting and responding to recurrent outbreaks of measles two years post the 2014 Ebola epidemic in Liberia., Methods: We conducted a descriptive study using the findings from Integrated Diseases Surveillance and Response (IDSR) 15 counties, National Public Health Institute of Liberia (NPHIL), National Public Health Reference Laboratory (NPHRL) and District Health Information Software (DIHS2) data conducted from October to December, 2017. We perused the outbreaks line lists and other key documents submitted by the counties to the national level from January 2016 to December 2017., Results: From January 2016 to December 2017, 2,954 suspected cases of measles were reported through IDSR. Four hundred sixty-seven (467) were laboratory confirmed (IgM-positive), 776 epidemiologically linked, 574 clinically confirmed, and 1,137 discarded (IgM-negative). Nine deaths out of 1817 cases were reported, a case fatality rate of 0.5%; 49% were children below the age of 5 years. Twenty-two percent (405/1817) of the confirmed cases were vaccinated while the vaccination status of 55% (994/1817) was unknown., Conclusion: Revitalization of IDSR contributed to increased detection and reporting of suspected cases of measles thus facilitating early identification and response to outbreaks. Priority needs to be given to increasing the uptake of routine immunization services, introducing a second dose of measles vaccine in the routine immunization program and conducting a high-quality supplementary measles immunization campaign for age group 1 to 10 years to provide protection for a huge cohort of susceptible., Competing Interests: The authors declare no competing interest.

Introduction: Liberia remains at high risk of poliovirus outbreaks due to importation. The country maintained certification level acute flaccid paralysis (AFP) surveillance indicators each year until 2014 due to Ebola outbreak. During this time, there was a significant drop in non-polio AFP rate to (1.2/100,000 population under 15 years) in 2015 from 2.9/100, 000 population in 2013, due to a variety of reasons including suspension on shipment of acute flaccid paralysis stool specimen to the polio regional lab in Abidjan, refocusing of surveillance officers attention solely on Ebola virus disease (EVD) surveillance, inactivation of national polio expert committee (NPEC) and National Certification Committee (NCC). The Ministry of Health (MOH) supported by partners worked to restore AFP surveillance post EVD outbreak and ensure that Liberia maintains its polio free certification., Methods: We conducted a desk review to summarize key activities conducted to restore acute flaccid paralysis (AFP) surveillance based on World Health Organization (WHO) AFP surveillance guidelines for Africa region. We also reviewed AFP surveillance indicators and introduction of new technologies. Data sources were from program reports, scientific and gray literature, AFP database, auto visual AFP detection and reporting (AVADAR) and ONA Servers. Data analysis was done using Microsoft excel and access spread sheets, ONA software and Geographic Information System (Arc GIS)., Results: AFP surveillance indicators improved with a rebound of non-polio AFP rate (NPAFP) rate from 1.2/100, 000 population under 15 years in 2015 to 4.3 in 2017. The stool adequacy rate at the national level also improved from 79% in 2016 to 82% in 2017, meeting the global target. The percentage of counties meeting the two critical AFP surveillance indicators NPAFP rate and stool adequacy improved from 47% in 2016 to 67% in 2017.The Last polio case reported in Liberia was in late 2010., Conclusion: There was significant improvement in the key AFP surveillance indicators such as NPAFP rate and stool adequacy with a 3.5 fold increase in NPAFP from 2014 to 2017. By 2017, the stool adequacy rate was up to target levels compared to 2016, which was below target level of 80%. The number of counties meeting target for the two critical AFP surveillance indicators also increased by 20% points between 2016 and 2017. Similarly there was approximately two-fold increase in the oral polio vaccines (OPV) coverage for the reported AFP cases between 2015 and 2017. Strategies employed to address gaps in AFP surveillance included enhanced active case search for AFP, re-instatement of laboratory testing, supportive supervision in addition to facilitating enhanced community engagement in surveillance activities. New technologies such as AVADAR Pilot, electronic integrated supportive supervision (ISS) and electronic surveillance (eSurv) tools were introduced to improve real time AFP case reporting. However, there remain residual gaps in AFP surveillance in the country especially at the sub-national level. Similarly, the newly introduced technologies will require continued funding and capacity building for MOH staff to ensure sustainability of the initiatives., Competing Interests: The authors declare no competing interest.

Objective: To canvass views about whether argon laser pretreatment to ischemic areas of retina would be acceptable if it resulted in a reduced burden of intravitreal injections., Method: A postal survey was mailed to all 813 patients under the care of the diabetic eye clinic at Singleton Hospital with 10 questions, explanatory information, and a stamp-addressed envelope available for returning completed questionnaires., Results: Patients were strongly supportive (9.14 out of 10) of the idea of undergoing laser pretreatment if it meant less injections were needed for diabetic macular edema., Conclusion: This is the first time any survey has analyzed patient attitude to laser pretreatment and showed that patients were strongly in favour if it was found to reduce the need for intravitreal injections., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the views of patients with diabetic retinopathy and maculopathy on their acceptance of virtual clinic review in place of face-to-face clinic appointments., Methods: A postal survey was mailed to all 813 patients under the care of the diabetic eye clinic at Singleton Hospital with 7 questions, explanatory information, and a stamped, addressed envelope available for returning completed questionnaires., Results: Four hundred and ninety-eight questionnaires were returned indicating that 86.1% were supportive of the idea of virtual clinics, although only 56.9% were prepared for every visit to be virtual. Of respondents, 6.6% not happy to attend any virtual clinic., Conclusion: This is by far the largest survey of patients' attitudes regarding attending virtual clinics and confirms that the vast majority are supportive of this mode of health care delivery., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Lassa fever (LF), a priority emerging pathogen likely to cause major epidemics, is endemic in much of West Africa and is difficult to distinguish from other viral hemorrhagic fevers, including Ebola virus disease (EVD). Definitive diagnosis requires laboratory confirmation, which is not widely available in affected settings. The public health action to contain a LF outbreak and the challenges encountered in an EVD-affected setting are reported herein., Methods: In February 2016, a rapid response team was deployed in Liberia in response to a cluster of LF cases. Active case finding, case investigation, contact tracing, laboratory testing, environmental investigation, risk communication, and community awareness raising were undertaken., Results: From January to June 2016, 53 suspected LF cases were reported through the Integrated Disease Surveillance and Response system (IDSR). Fourteen cases (26%) were confirmed for LF, 14 (26%) did not have a sample tested, and 25 (47%) were classified as not a case following laboratory analysis. The case fatality rate in the confirmed cases was 29%. One case of international exportation was reported from Sweden. Difficulties were identified in timely specimen collection, packaging, and transportation (in confirmed cases, the time from sample collection to sample result ranged from 2 to 64 days) and a lack of response interventions for early cases., Conclusions: The delay in response to this outbreak could have been related to a number of challenges in this EVD-affected setting: a need to strengthen the IDSR system, develop preparedness plans, train rapid response teams, and build laboratory capacity. Prioritizing these actions will aid in the timely response to future outbreaks., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)., Methods: In mice, the effects of MEK inhibition, via selumetinib, and anti-CTLA-4 on immune responses to keyhole limpet haemocyanin (KLH) immunization were monitored using ex vivo functional assays with splenocytes. In a KRAS-mutant CT26 mouse colorectal cancer model, the impact on the tumor microenvironment (TME) and the spleen were evaluated by flow cytometry. The TME was further examined by gene expression and immunohistochemical analyses. The combination and sequencing of selumetinib and anti-CTLA-4 were also evaluated in efficacy studies using the CT26 mouse syngeneic model., Results: Anti-CTLA-4 enhanced the generation of KLH specific immunity following KLH immunization in vivo; selumetinib was found to reduce, but did not prevent, this enhancement of immune response by anti-CTLA-4 in vivo. In the CT26 mouse model, anti-CTLA-4 treatment led to higher expression levels of the immunosuppressive mediators, Cox-2 and Arg1 in the TME. Combination of anti-CTLA-4 with selumetinib negated this up-regulation of Cox-2 and Arg1, reduced the frequency of CD11 + Ly6G + myeloid cells, and led to the accumulation of differentiating monocytes at the Ly6C + MHC + intermediate state in the tumor. We also report that MEK inhibition had limited impact on anti-CTLA-4-mediated increases in T-cell infiltration and T-cell activation in CT26 tumors. Finally, we show that pre-treatment, but not concurrent treatment, with selumetinib enhanced the anti-tumor activity of anti-CTLA-4 in the CT26 model., Conclusion: These data provide evidence that MEK inhibition can lead to changes in myeloid cells and immunosuppressive factors in the tumor, thus potentially conditioning the TME to facilitate improved response to anti-CTLA-4 treatment. In summary, the use of MEK inhibitors to alter the TME as an approach to enhance the activities of immune checkpoint inhibitors warrants further investigation in clinical trials.

Antibodies that target cell-surface molecules on T cells can enhance anti-tumor immune responses, resulting in sustained immune-mediated control of cancer. We set out to find new cancer immunotherapy targets by phenotypic screening on human regulatory T (Treg) cells and report the discovery of novel activators of tumor necrosis factor receptor 2 (TNFR2) and a potential role for this target in immunotherapy. A diverse phage display library was screened to find antibody mimetics with preferential binding to Treg cells, the most Treg-selective of which were all, without exception, found to bind specifically to TNFR2. A subset of these TNFR2 binders were found to agonise the receptor, inducing iκ-B degradation and NF-κB pathway signalling in vitro. TNFR2 was found to be expressed by tumor-infiltrating Treg cells, and to a lesser extent Teff cells, from three lung cancer patients, and a similar pattern was also observed in mice implanted with CT26 syngeneic tumors. In such animals, TNFR2-specific agonists inhibited tumor growth, enhanced tumor infiltration by CD8+ T cells and increased CD8+ T cell IFN-γ synthesis. Together, these data indicate a novel mechanism for TNF-α-independent TNFR2 agonism in cancer immunotherapy, and demonstrate the utility of target-agnostic screening in highlighting important targets during drug discovery.

The canonical atrial myocyte (AM) is characterized by sparse transverse tubule (TT) invaginations and slow intracellular Ca2+ propagation but exhibits rapid contractile activation that is susceptible to loss of function during hypertrophic remodeling. Here, we have identified a membrane structure and Ca2+-signaling complex that may enhance the speed of atrial contraction independently of phospholamban regulation. This axial couplon was observed in human and mouse atria and is composed of voluminous axial tubules (ATs) with extensive junctions to the sarcoplasmic reticulum (SR) that include ryanodine receptor 2 (RyR2) clusters. In mouse AM, AT structures triggered Ca2+ release from the SR approximately 2 times faster at the AM center than at the surface. Rapid Ca2+ release correlated with colocalization of highly phosphorylated RyR2 clusters at AT-SR junctions and earlier, more rapid shortening of central sarcomeres. In contrast, mice expressing phosphorylation-incompetent RyR2 displayed depressed AM sarcomere shortening and reduced in vivo atrial contractile function. Moreover, left atrial hypertrophy led to AT proliferation, with a marked increase in the highly phosphorylated RyR2-pS2808 cluster fraction, thereby maintaining cytosolic Ca2+ signaling despite decreases in RyR2 cluster density and RyR2 protein expression. AT couplon "super-hubs" thus underlie faster excitation-contraction coupling in health as well as hypertrophic compensatory adaptation and represent a structural and metabolic mechanism that may contribute to contractile dysfunction and arrhythmias.

Calcium-induced calcium release is the principal mechanism that triggers the cell-wide [Ca(2+)]i transient that activates muscle contraction during cardiac excitation-contraction coupling (ECC). Here, we characterize this process in mouse cardiac myocytes with a novel mathematical action potential (AP) model that incorporates realistic stochastic gating of voltage-dependent L-type calcium (Ca(2+)) channels (LCCs) and sarcoplasmic reticulum (SR) Ca(2+) release channels (the ryanodine receptors, RyR2s). Depolarization of the sarcolemma during an AP stochastically activates the LCCs elevating subspace [Ca(2+)] within each of the cell's 20,000 independent calcium release units (CRUs) to trigger local RyR2 opening and initiate Ca(2+) sparks, the fundamental unit of triggered Ca(2+) release. Synchronization of Ca(2+) sparks during systole depends on the nearly uniform cellular activation of LCCs and the likelihood of local LCC openings triggering local Ca(2+) sparks (ECC fidelity). The detailed design and true SR Ca(2+) pump/leak balance displayed by our model permits investigation of ECC fidelity and Ca(2+) spark fidelity, the balance between visible (Ca(2+) spark) and invisible (Ca(2+) quark/sub-spark) SR Ca(2+) release events. Excess SR Ca(2+) leak is examined as a disease mechanism in the context of "catecholaminergic polymorphic ventricular tachycardia (CPVT)", a Ca(2+)-dependent arrhythmia. We find that that RyR2s (and therefore Ca(2+) sparks) are relatively insensitive to LCC openings across a wide range of membrane potentials; and that key differences exist between Ca(2+) sparks evoked during quiescence, diastole, and systole. The enhanced RyR2 [Ca(2+)]i sensitivity during CPVT leads to increased Ca(2+) spark fidelity resulting in asynchronous systolic Ca(2+) spark activity. It also produces increased diastolic SR Ca(2+) leak with some prolonged Ca(2+) sparks that at times become "metastable" and fail to efficiently terminate. There is a huge margin of safety for stable Ca(2+) handling within the cell and this novel mechanistic model provides insight into the molecular signaling characteristics that help maintain overall Ca(2+) stability even under the conditions of high SR Ca(2+) leak during CPVT. Finally, this model should provide tools for investigators to examine normal and pathological Ca(2+) signaling characteristics in the heart., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

There are many differential diagnoses in investigating patients who present with retinal vasculitis, and the laboratory investigations used to investigate this have low-to-moderate sensitivity and/or specificity. Diagnoses include conditions such as tuberculosis or sarcoidosis, which may require long courses of antibiotics or immunosuppression. Influenza vaccination has been recognised as a cause of vasculitis for decades, although a purely ocular presentation is rare. We present a case of a 78-year-old Caucasian woman presenting with a single vessel arterial vasculitis of the right eye 8 weeks following influenza vaccination at her local general practitioner practice. We encourage ophthalmologists, rheumatologists and uveitis specialists to consider influenza vaccine as a cause of ocular vasculitis if the vaccine has been recently administered., (2015 BMJ Publishing Group Ltd.)

Background: As West Africa continues to suffer from a deadly Ebola epidemic, the national health sectors struggle to minimize the damages and stop the spread of disease., Methods: A cohort of inhabitants of a small village and an Ebola hot zone in Sinoe County of Liberia was followed on a day-by-day basis to search for new cases and to minimize the spread of Ebola to the other community members or to other regions. Technical, clinical, and humanistic aspects of the response are discussed in this report., Results: Of the 22 confirmed Ebola cases in Sinoe County since the beginning of outbreak (June 16, 2014), 7 cases were inhabitants of Polay Town, a small village 5.5 miles east of Greenville, the Sinoe County capital. After the last wave of outbreak at the beginning of December, enhanced response activity provided essential coordination and mobilized the resources to stop the epidemic. Despite unprotected contacts in crowded houses, no new cases were detected among the contact families, or in the surrounding houses or communities., Conclusions: Strong national mobilization in a decentralized but harmonized system at the community level has been of great value in controlling the epidemic in Liberia. The major interventions include epidemiological surveillance, public information dissemination, effective communication, case management, and infection control., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Providing intravitreal ranibizumab therapy for neovascular age related macular degeneration (nARMD) is a source of increasing strain for many UK eye departments. Whilst most units attempt to adhere to the product licence of following up patients at four weekly intervals; delays in follow up appointments can and do occur. We aim to see if mean follow up intervals during the maintenance phase are correlated with visual outcomes at one year and perform a multivariate analysis of patient factors in a bit to understand the factors affecting visual acuity outcomes., Method: A continuously updated prospective audit of patients receiving ranibizumab therapy at the Royal Gwent Hospital was accessed and a coefficient of determination and Spearman's rank test undertaken to see whether mean follow up delays resulted in visual acuity penalties after nine months of maintenance. Multivariate analysis using ANOVA was then undertaken to examine in more detail the various factors affecting visual acuity outcomes., Results: 805 eyes of 708 patients were included in the study. Mean follow up intervals varied between 28.0 and 96.3 days over the first six treatments of the maintenance phase (mean 49.2 - SD 10.7) with a mean change in visual acuity from baseline of +7.1 letters at 12 weeks and +4.6 letters at 52 weeks. There was a negative correlation seen between visual acuity gains after nine months of the maintenance phase and increasing clinic follow up times although Spearman's rank analysis demonstrated a correlation coefficient of only -0.078, which was not statistically significant. Variability in follow up appointments resulting in worse outcomes was however significant (p < 0.01), as was increasing age at presentation (p = 0.04). Smoking was found to decrease age of presentation by six years (74.2 years vs 80.0 years). The adjusted R (2) for the whole analysis was 0.44., Conclusion: Wide variation in follow up intervals was associated with a worse visual acuity outcome although longer mean follow up interval was not. Smokers presented at a significantly younger age than non-smokers or ex-smokers. This was a large study with an adjusted R (2) of 0.44. The results are relevant to other macular degeneration service providers around the world.