Progress Towards Elimination of Trachoma in Kenya 2017-2020.

PURPOSE: Trachoma is endemic in Kenya. Since baseline trachoma surveys in 2004, a concerted programme has been undertaken to reduce the prevalence of disease. Here, we report on trachoma prevalence surveys carried out between 2017 and 2020 after interventions were implemented in some areas for trachoma elimination purposes. METHODS: A total of 48 cross-sectional population-based trachoma prevalence surveys were conducted in 39 evaluation units (EUs; covering 45 subcounties) of Kenya between 2017 and 2020. Thirty EUs were surveyed once and nine EUs were surveyed twice over this period. Individuals ≥ 1 year old were assessed for trachomatous inflammation-follicular (TF), trachomatous inflammation-intense (TI) and trichiasis. Data were collected on household access to water, sanitation and hygiene (WASH). RESULTS: A total of 147,573 people were examined. At the end of 2020, in the 39 EUs surveyed, the prevalence of TF in 1-9-year-olds was ≥5% in 11 EUs and the prevalence of trichiasis unknown to the health system in individuals aged ≥15 years was ≥0.2% in 25 EUs. A small minority of households (median <50% for all indicators) had access to improved WASH facilities. CONCLUSION: Kenya has made excellent progress towards elimination of trachoma as a public health problem. However, there is more work to do. Between one and three rounds of antibiotic mass drug administration are required in 11 EUs. Sustained investment in surgical provision, continued TT case-finding, promotion of facial cleanliness and environmental improvement are required throughout the surveyed area.

Measurements of neutrino oscillation parameters from the T2K experiment using 3.6×1021 protons on target.

The T2K experiment presents new measurements of neutrino oscillation parameters using 19.7(16.3)×1020 protons on target (POT) in (anti-)neutrino mode at the far detector (FD). Compared to the previous analysis, an additional 4.7×1020 POT neutrino data was collected at the FD. Significant improvements were made to the analysis methodology, with the near-detector analysis introducing new selections and using more than double the data. Additionally, this is the first T2K oscillation analysis to use NA61/SHINE data on a replica of the T2K target to tune the neutrino flux model, and the neutrino interaction model was improved to include new nuclear effects and calculations. Frequentist and Bayesian analyses are presented, including results on sin2θ13 and the impact of priors on the δCP measurement. Both analyses prefer the normal mass ordering and upper octant of sin2θ23 with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on sin2θ13 from reactors, sin2θ23=0.561-0.032+0.021 using Feldman-Cousins corrected intervals, and Δm322=2.494-0.058+0.041×10-3eV2 using constant Δχ2 intervals. The CP-violating phase is constrained to δCP=-1.97-0.70+0.97 using Feldman-Cousins corrected intervals, and δCP=0,π is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than 2σ credible level using a flat prior in δCP, and just below 2σ using a flat prior in sinδCP. When the external constraint on sin2θ13 is removed, sin2θ13=28.0-6.5+2.8×10-3, in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses.

Clinicopathologic and immunophenotypic features in dogs with presumptive large granular lymphocyte leukaemia.

Large granular lymphocytic leukaemia (LGLL) has been described in a range of species but has been most commonly reported in humans and dogs. In both species, this neoplasia exhibits diversity in both phenotype and biological behaviour with phenotype only partially predicting behaviour. There is currently little knowledge of concurrent haematological and serum biochemistry features or concurrent occurrence of distinct neoplasia in canine LGLL cases. This study presents a canine case series and defines haematological parameters, novel serum biochemistry findings and phenotype of the large granular lymphocytes in an Australian case series. Neutrophilia was the most common haematological abnormality, identified in 43% of dogs, and 84% of dogs with biochemistry data available had elevated serum gamma-glutamyl transferase. Five of the 40 dogs in this study exhibited concurrent neoplasia during the period of the study, demonstrating this is a relatively common clinical outcome in canine LGLL cases. In agreement with previous canine and human studies, the most common LGLL phenotype in dogs is CD3+, CD4- and CD8+. Further work is needed to define the variables predictive of the biological behaviour of LGLL in dogs.

How to diagnose and treat acute pulmonary hypertension when you have no cardiology support.

Acute pulmonary hypertension (aPH) is a complex, physiology-driven disorder that causes critical illness in newborns, the hallmark of which is elevated pressure in the pulmonary vascular bed. Several underlying hemodynamic phenotypes exist, including classic arterial aPH with resistance-driven elevations in pulmonary arterial pressure (PAP), alongside flow-driven aPH from left-to-right shunt lesions, and primary left ventricular dysfunction with pulmonary venous hypertension and elevated left atrial pressure. Targeted neonatal echocardiography (TnECHO) is an important tool for evaluation of hemodynamics in aPH and is highly useful for evaluating modulators of disease and targeting cardiovascular therapy. The diagnostic approach to aPH includes confirmation of elevation of PAP, evaluation of the cause and exclusion of structural cardiac disease, assessment of the response of the myocardium to adverse loading conditions, and appraisal of the adequacy of systemic blood flow. Therapeutic goals include support of right ventricular (RV) function, RV afterload reduction, and selection of cardiotropic agents that support underlying pathophysiology without adverse effects on heart rate or pulmonary vascular resistance in addition to routine supportive intensive care. Training programs for TnECHO exist across multiple jurisdictions and strong correlation with pediatric cardiology assessment has been demonstrated. Future directions include adapting TnECHO training with a greater focus on achieving competency, and further research into the role of the modality in providing individualized cardiovascular care for patients with heterogenous underlying physiology, and its effect on key neonatal outcomes.

Protecting the brain of the micropreemie.

Advances in perinatal care have seen substantial improvements in survival without disability for extremely preterm infants. Protecting the developing brain and reducing neurodevelopmental sequelae of extremely preterm birth are strategic priorities for both research and clinical care. A number of evidence-based interventions exist for neuroprotection in micropreemies, inclusive of prevention of preterm birth and multiple births with implantation of only one embryo during in vitro fertilisation, as well as antenatal care to optimize fetal wellbeing, strategies for supporting neonatal transition, and neuroprotective developmental care. Avoidance of complications that trigger ischemia and inflammation is vital for minimizing brain dysmaturation and injury, particularly of the white matter. Neurodevelopmental surveillance, early diagnosis of cerebral palsy and early intervention are essential for optimizing long-term outcomes and quality of life. Research priorities include further evaluation of putative neuroprotective agents, and investigation of common neonatal interventions in trials adequately powered to assess neurodevelopmental outcome.

Haemoprotozoa in wild short-beaked echidnas (Tachyglossus aculeatus).

The occurrence and clinical significance of the protozoal parasite reported as Hepatozoon tachyglossi in wild short-beaked echidnas (Tachyglossis aculeatus) have long been uncertain, as has its potential as a prognostic indicator. This retrospective survey of free-ranging short-beaked echidnas admitted to a wildlife hospital used morphological evidence to identify a H. tachyglossi prevalence of 56%, with parasitaemias affecting 0%-36% of monocytes. There was no statistical association between H. tachyglossi intensity and clinical status (P-value = 0.12; 95% confidence interval = 0.1 to 1.3), nor between the presence of H. tachyglossi and age, reason for admission, outcome, season or location. Piroplasms, presumed to be Theileria tachyglossi, were concurrently identified in the erythrocytes of 88% of short-beaked echidnas with no association between age, outcome, season or location, but a statistical association with the location where the animal was found (either on a road, airport runway, exposed urban area, or entangled). Given the current results, intracellular parasitism due to H. tachyglossi may be considered as an incidental finding on haematologic examination of short-beaked echidnas and is likely not an effective prognostic indicator. Further research using molecular tools is required to resolve the uncertain identity of H. tachyglossi which has been based on morphologic characteristics alone.

Heterogenous bone response to biologic DMARD therapies in rheumatoid arthritis patients and their relationship to functional indices.

Objectives: Previous studies of high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of hand joints in patients with rheumatoid arthritis (RA) have suggested that erosion healing may occur. Our objective was to examine changes in erosion volume, joint space width (JSW), bone mineral density (BMD), and bone remodelling, and their association with clinical outcomes and measures of patient hand function.Method: We examined 48 patients who achieved a good response to a newly initiated biologic therapy. HR-pQCT images of the dominant hands' second and third metacarpophalangeal joints were obtained 3 and 12 months after therapy initiation. Bone erosion volume, JSW, BMD, and bone remodelling were quantified from HR-pQCT images, with improvement, no change (unchanged), or progression in these measures determined by least significant change. Disease activity and hand function measures were collected.Results: There were no significant group changes in HR-pQCT outcomes over the 9 month period. Twenty-two patients had total erosion volumes that remained unchanged, nine showed improvement, and two progressed. The majority of JSW and BMD measures remained unchanged. There was a significant association between the baseline Health Assessment Questionnaire score and the change in minimum JSW, but no other significant associations between HR-pQCT outcomes and function were observed.Conclusions: The vast majority of patients maintained unchanged JSW and BMD over the course of follow-up. Significant improvements in total erosion volume occurred in 27% of patients, suggesting that biologic therapies may lead to erosion healing in some patients, although this did not have an impact on self-reported and demonstrated hand function.

Using 3D image registration to maximize the reproducibility of longitudinal bone strength assessment by HR-pQCT and finite element analysis.

We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D image registration to account for misalignment between images. This reduced variability in longitudinal FE estimates and improved our ability to measure in vivo changes in HR-pQCT studies of bone strength. INTRODUCTION: We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D rigid-body registration (3DR) to maximize reproducibility by accounting for misalignment between images. METHODS: In our proposed approach, we used the full common bone volume defined by 3DR to estimate standard FE parameters. Using standard HR-pQCT imaging protocols, we validated the 3DR approach with ex vivo samples of the distal radius (n = 10, four repeat scans) by assessing whether 3DR can reduce measurement variability from repositioning error. We used in vivo data (n = 40, five longitudinal scans) to assess the sensitivity of 3DR to detect changes in bone strength at the distal radius by the standard deviation of the rate of change (σ), where the ideal value of σ is minimized to define true change. FE estimates by 3DR were compared to estimates by no registration (NR) and slice-matching (SM). RESULTS: Group-wise comparisons of ex vivo variation (CVRMS, %) found that FE measurement precision was improved by SM (CVRMS < 0.80%) and 3DR (CVRMS < 0.62%) compared to NR (CVRMS~2%), and 3DR was advantageous as repositioning error increased. Longitudinal in vivo reproducibility was minimized by 3DR for failure load estimates (σ = 0.008 kN/month). CONCLUSION: Although 3D registration cannot negate motion artifacts, it plays an important role in detecting and reducing variability in FE estimates for longitudinal HR-pQCT data and is well suited for estimating effects of interventions in in vivo longitudinal studies of bone strength.

Opportunistic CT screening predicts individuals at risk of major osteoporotic fracture.

Millions of CT scans are performed annually and could be also used to opportunistically assess musculoskeletal health; however, it is unknown how well this secondary assessment relates to osteoporotic fracture. This study demonstrates that opportunistic CT screening is a promising tool to predict individuals with previous osteoporotic fracture. INTRODUCTION: Opportunistic computed tomography (oCT) screening for osteoporosis and fracture risk determination complements current dual X-ray absorptiometry (DXA) diagnosis. This study determined major osteoporotic fracture prediction by oCT at the spine and hip from abdominal CT scans. METHODS: Initial 1158 clinical abdominal CT scans were identified from administrative databases and were the basis to generate a cohort of 490 men and women with suitable abdominal CT scans. Participant CT scans met the following criteria: over 50 years of age, the scan had no image artifacts, and the field-of-view included the L4 vertebra and proximal femur. A total of 123 participants were identified as having previously suffered a fracture within 5 years of CT scan date. Fracture cause was identified from clinical data and used to create a low-energy fracture sub-cohort. At each skeletal site, bone mineral density (BMD) and finite element (FE)-estimated bone strength were determined. Logistic regression predicted fracture and receiver-operator characteristic curves analyzed prediction capabilities. RESULTS: In participants with a fracture, low-energy fractures occurred in 88% of women and 79% of men. Fracture prediction by combining both BMD and FE-estimated bone strength was not statistically different than using either BMD or FE-estimated bone strength alone. Predicting low-energy fractures in women determined the greatest AUC of 0.710 by using both BMD and FE-estimated bone strength. CONCLUSIONS: oCT screening using abdominal CT scans is effective at predicting individuals with previous fracture at major osteoporotic sites and offers a promising screening tool for skeletal health assessment.

Picowatt calorimeter for optical absorption spectroscopy.

An optical picowatt calorimeter at 4 K is demonstrated to measure absorption spectra from 330 nm to 1700 nm of optical samples. The minimum detectable absorbed power is 10 pW, resulting in absorption sensitivities of 0.3 ppm for 30 µW of incident power from a tunable source and 0.6 ppb for 15 mW laser excitation. Active temperature stabilization of main components of the cryogen-free cryostat and the use of paramagnetic temperature sensors with superconducting quantum interference device readout provided a low noise environment (700 nK temperature rms) and nK temperature resolution.

Developing a comprehensive database with sensitive health information: A profile of people living with HIV in Newfoundland and Labrador, Canada.

INTRODUCTION: Developing a comprehensive cohort of people living with HIV (PLHIV) to help improve healthcare has long been the vision of researchers, clinicians and decision makers. The development of this kind of database is challenging and requires strict adherence to privacy and confidentiality policies. We explored procedures, activities and events in database development. OBJECTIVES: To understand processes of developing a database with sensitive health information in Newfoundland and Labrador (NL), and to investigate procedures and activities to develop the database within its environmental context. METHODS: A narrative case study was used to explain the challenges and procedures involved in developing a database for our population. The development of the PLHIV cohort in NL is provided as an example to demonstrate the complexity of the process. We linked three datasets that included patient-level data for PLHIV: 1. laboratory data; 2. HIV clinic data; 3. health administrative data, which allowed for the creation of a large database containing many variables describing the PLHIV cohort in the province. RESULTS: We developed a de-identified cohort of 251 PLHIV that contained 178 variables. Our case study showed database development is an iterative process. The main challenges were ensuring patient privacy and data confidentiality are not compromised and working with multi-custodian data. These challenges were addressed by establishing a data governance team. CONCLUSIONS: It is important that policy be implemented to merge siloed data sources in order to provide researchers with accurate and complete data that is required to conduct sound and precise research with maximum benefits for treatment and policy-making to improve health outcomes.

Differences in fracture prevalence and in bone mineral density between Chinese and White Canadians: the Canadian Multicentre Osteoporosis Study (CaMos).

Fracture determinants differ between Canadians of Chinese and White descent, the former constituting the second largest visible minority group in Canada. The results of this study support the importance of characterizing bone health predictors in Canadians of different ethnicity to improve population-specific fracture prevention and treatment strategies. PURPOSE: We aimed to compare clinical risk factors, bone mineral density, prevalence of osteoporosis, and fractures between Chinese and White Canadians to identify ethnicity-specific risks. METHODS: We studied 236 Chinese and 8945 White Canadians aged 25+ years from the Canadian Multicentre Osteoporosis Study (CaMos). The prevalence of osteoporosis using ethnicity-specific peak bone mass (PBM), and of prior and incident low trauma fractures were assessed and compared between groups. Linear regressions, adjusting for age and anthropometric measures, were used to examine the association between baseline and 5-year changes in BMD and ethnicity. RESULTS: Chinese participants had shorter stature, lower BMI, and lower rate of falls than White participants. Adjusted models showed no significant differences in baseline BMD between ethnic groups except in younger men where total hip BMD was 0.059 g/cm2 (0.009; 0.108) lower in Chinese. Adjusted 5-year BMD change at lumbar spine was higher in older Chinese women and men compared with Whites. When using Chinese-specific PBM, the prevalence of osteoporosis in Chinese women was 2-fold lower than when using that of White women The prevalence of fractures was higher in White women compared with Chinese with differences up to 14.5% (95% CI 9.2; 19.7) and 10.5% (95% CI 4.5-16.4) in older White men. Incident fractures were rare in young Chinese compared with White participants and not different in the older groups. CONCLUSION: Our results support the importance of characterizing bone strength predictors in Chinese Canadians and the development of ethnicity-specific fracture prediction and prevention strategies.

Effect of high-dose vitamin D supplementation on peripheral arterial calcification: secondary analysis of a randomized controlled trial.

Although high-dose vitamin D supplementation is common, effects on arterial calcification remain unexplored. Tibial artery calcification was identified and quantified over 3 years in participants randomized to 400, 4000, or 10,000 IU vitamin D3 daily. High-dose vitamin D supplementation did not affect the development or progression of arterial calcification. INTRODUCTION: To determine whether vitamin D supplementation has a dose-dependent effect on development and progression of arterial calcification. METHODS: This was a secondary analysis of the Calgary Vitamin D Study, a 3-year, double-blind, randomized controlled trial conducted at a single-center in Calgary, Canada. Participants were community-dwelling adults aged 55-70 years with serum 25-hydroxyvitamin D 30-125 nmol/L. Participants were randomized 1:1:1 to receive vitamin D3 400, 4000, or 10,000 IU/day for 3 years. Tibial artery calcification was identified and quantified (in milligrams of hydroxyapatite, mgHA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6, 12, 24, and 36 months. Changes in calcification over time and treatment group interaction were evaluated using a constrained linear mixed effects model. RESULTS: Of 311 randomized participants, 302 (400: 105, 4000: 96, 10,000: 101) were eligible for analysis of arterial calcification (54% male, mean (SD) age 62 (4) years, mean (SD) 25-hydroxyvitamin D 78.9 (19.9) nmol/L). At baseline, 85 (28%) had tibial artery calcification, and mean (95% CI) calcification quantity was 2.8 mgHA (95% CI 1.7-3.9). In these 85 participants, calcification quantity increased linearly by 0.020 mgHA/month (95% CI 0.012-0.029) throughout the study, with no evidence of a treatment-group effect (p = 0.645 for interaction). No participants developed new arterial calcifications during the study. CONCLUSIONS: In this population of community-dwelling adults who were vitamin D replete at baseline, supplementation with vitamin D 400, 4000, or 10,000 IU/day did not have differential effects on the development or progression of arterial calcification over 3 years. TRIAL REGISTRATION: clinicaltrials.gov (NCT01900860).

Longitudinal bone microarchitectural changes are best detected using image registration.

Longitudinal studies of bone using high-resolution medical imaging may result in non-physiological measurements of longitudinal changes. In this study, we determined that three-dimensional image processing techniques best capture realistic longitudinal changes in bone density and should therefore be used with high-resolution imaging when studying bone changes over time. INTRODUCTION: The purpose of this study was to determine which longitudinal analysis technique (no registration (NR), slice-match (SM) registration, or three-dimensional registration (3DR)) produced the most realistic longitudinal changes in a 3-year study of bone density and structure using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: We assessed HR-pQCT scans of the distal radius and tibia for men and women (N = 40) aged 55-70 years at baseline and 6, 12, 24, and 36 months. To evaluate which longitudinal analysis technique (NR, SM, or 3DR) best captured physiologically reasonable 3-year changes, we calculated the standard deviation of the absolute rate of change in each bone parameter. The data were compared between longitudinal analysis techniques using repeated measures ANOVA and post hoc analysis. RESULTS: As expected, both SM and 3DR better captured physiological longitudinal changes than NR. At the tibia, there were no differences between SM and 3DR; however, at the radius where precision was lower, 3DR produced better results for total bone mineral density. CONCLUSIONS: At least SM or 3DR should be implemented in longitudinal studies using HR-pQCT. 3DR is preferable, particularly at the radius, to ensure that physiological changes in bone density are observed.

Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography.

INTRODUCTION: The application of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess bone microarchitecture has grown rapidly since its introduction in 2005. As the use of HR-pQCT for clinical research continues to grow, there is an urgent need to form a consensus on imaging and analysis methodologies so that studies can be appropriately compared. In addition, with the recent introduction of the second-generation HrpQCT, which differs from the first-generation HR-pQCT in scan region, resolution, and morphological measurement techniques, there is a need for guidelines on appropriate reporting of results and considerations as the field adopts newer systems. METHODS: A joint working group between the International Osteoporosis Foundation, American Society of Bone and Mineral Research, and European Calcified Tissue Society convened in person and by teleconference over several years to produce the guidelines and recommendations presented in this document. RESULTS: An overview and discussion is provided for (1) standardized protocol for imaging distal radius and tibia sites using HR-pQCT, with the importance of quality control and operator training discussed; (2) standardized terminology and recommendations on reporting results; (3) factors influencing accuracy and precision error, with considerations for longitudinal and multi-center study designs; and finally (4) comparison between scanner generations and other high-resolution CT systems. CONCLUSION: This article addresses the need for standardization of HR-pQCT imaging techniques and terminology, provides guidance on interpretation and reporting of results, and discusses unresolved issues in the field.

Search for Electron Antineutrino Appearance in a Long-Baseline Muon Antineutrino Beam.

Electron antineutrino appearance is measured by the T2K experiment in an accelerator-produced antineutrino beam, using additional neutrino beam operation to constrain parameters of the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) mixing matrix. T2K observes 15 candidate electron antineutrino events with a background expectation of 9.3 events. Including information from the kinematic distribution of observed events, the hypothesis of no electron antineutrino appearance is disfavored with a significance of 2.40σ and no discrepancy between data and PMNS predictions is found. A complementary analysis that introduces an additional free parameter which allows non-PMNS values of electron neutrino and antineutrino appearance also finds no discrepancy between data and PMNS predictions.

Nanolaminate-based design for UV laser mirror coatings.

With ever-increasing laser power, the requirements for ultraviolet (UV) coatings increase continuously. The fundamental challenge for UV laser-resistant mirror coatings is to simultaneously exhibit a high reflectivity with a large bandwidth and high laser resistance. These characteristics are traditionally achieved by the deposition of laser-resistant layers on highly reflective layers. We propose a "reflectivity and laser resistance in one" design by using tunable nanolaminate layers that serve as an effective layer with a high refractive index and a large optical bandgap. An Al2O3-HfO2 nanolaminate-based mirror coating for UV laser applications is experimentally demonstrated using e-beam deposition. The bandwidth, over which the reflectance is >99.5%, is more than twice that of a traditional mirror with a comparable overall thickness. The laser-induced damage threshold is increased by a factor of ~1.3 for 7.6 ns pulses at a wavelength of 355 nm. This tunable, nanolaminate-based new design strategy paves the way toward a new generation of UV coatings for high-power laser applications.

Cryptococcus neoformans var grubii meningoencephalitis in a patient on fingolimod for relapsing-remitting multiple sclerosis: Case report and review of published cases.

INTRODUCTION: Fingolimod, a sphingosine-1-phosphate modulator used in the treatment of relapsing-remitting multiple sclerosis, has been associated with several cases of cryptococcosis. CASE REPORT: We present a case of Cryptococcal meningoencephalitis attributable to Cryptococcus neoformans var. grubii, in a 58-year-old bird-keeper from Australia, after 7 years of fingolimod therapy. We discuss this in the context of previously reported cases, our understanding of fingolimod immune modulation, and known Cryptococcus pathobiology. CONCLUSION: We suggest consideration of harm minimisation behaviours in patients requiring fingolimod, particularly in those with profound CD4 lymphopenia. Furthermore, we echo the call for improved post-marketing surveillance systems to determine the epidemiology of atypical infections with novel immunomodulatory treatments.