Mean Lag Time Research Articles

Trends in Presentation and Management of Endogenous Hyperinsulinaemic Hypoglycaemia Over the Last Three Decades at a Tertiary Care Centre (1992-2022).

Endogenous hyperinsulinaemic hypoglycaemia (EHH) is characterized by inappropriate insulin secretion from pancreatic beta cells despite low blood glucose concentrations. We aimed to evaluate the secular changes in presentation and management of EHH due to insulinoma/non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) at our centre. This was a single-centre ambispective study (2014-2022). The clinical, biochemical, hormonal and radiological parameters (n = 63) collected as part of this study were compared with our earlier studies (1992-2005, n = 31; and 2006-2013, n = 35) and with other centres across the world. A total of 63 patients (39 males) with a preoperative diagnosis of EHH (insulinoma, n = 58; and NIPHS, n = 5) and a mean age of 40.7 years were studied. The mean lag time from the onset of symptoms to diagnosis decreased from 4.6 years during the first study period to 1.9 years during this study period. However, the majority presented with fasting hypoglycaemia of 98.4%, and both fasting and postprandial hypoglycaemia of 32%. Exclusive postprandial hypoglycaemia was present in 1.7% of insulinoma. A histopathological diagnosis of insulinoma was made in 52 patients and nesidioblastosis in two patients. Intraoperative ultrasonography (IOUS) and intraoperative palpation (IOP) yielded 100% sensitivity, while endoscopic ultrasonography (EUS) and 68Ga-DOTA-Exendin-4 positron emission tomography/computed tomography (PET/CT) yielded sensitivity of 86% and 85%, respectively, for localizing insulinoma. Resolution of hypoglycaemia was noted in 53 of 57 (93%) patients who underwent surgery with a preoperative diagnosis of insulinoma. We observed a trend towards earlier diagnosis of EHH, increased patient numbers and availability of nuclear imaging techniques for preoperative localization in the last decade compared to earlier.

Induction into viable but non culturable state and outgrowth heterogeneity of Listeria monocytogenes is affected by stress history and type of growth

Exposure to sublethal stresses related to food-processing may induce a heterogenous mixture of cells that co-exist, comprising healthy, sublethally injured, dormant and dead cells. Heterogeneity in survival capacity and dormancy of single cells may impede the detection of foodborne pathogens. In this study, we exposed Listeria monocytogenes Scott A strain, to peracetic acid (PAA; 20–40 ppm) and to acidic conditions (hydrochloric (HCl) and acetic (AA) acid, adjusted to pH 2.7–3.0, to evaluate the resuscitation capacity and outgrowth kinetics of metabolically active cells in two different media. Injury and the viable-but-non-culturable (VBNC) status of cells were assessed by flow cytometry using CFDA (metabolically active) and PI (dead) staining. Stressed CFDA+PI− cells were sorted on Tryptic Soy (TS) Agar or in TS broth, both supplemented with 0.6 % Yeast Extract (TSAYE or TSBYE), to evaluate culturability. Resuscitation capacity of CFDA+PI−sorted cells (10 events/well) was monitored by visual inspection on TSAYE and by optical density measurement in TSBYE for 5 days. Sorting of L. monocytogenes viable cells (CFDA+PI−) in Ringer's solution on TSAYE and TSBYE showed 100 % recovery in both media (control condition), while the mean lag time in TSBYE was 9.6 h. Treatment with 20 ppm PAA for 90 and 180 min resulted in 74.79 % and 85.82 % of non-culturable cells in TSBYE and increased the average lag time to 41.7 h and 43.8 h, respectively, compared to the control (9.6 h). The longest average lag time (79.5 h) was detected after treatment with 30 ppm PAA for 90 min, while at the same condition sorting of CFDA+PI− cells resulted in 95.05 % and 93.94 % non-culturable cells on TSAYE and TSBYE, respectively. The highest percentage of wells with non-culturable cells (96.17 %) was detected on TSAYE after treatment with 40 ppm PAA for 30 min. Fractions of VBNC cells were detected in TSBYE after treatment with HCl pH 3.0 for 60 and 240 min, and in TSAYE and TSBYE after exposure to AA pH 2.7. Treatment with AA pH 2.7 for 150–300 min increased the range of recorded lag time values compared to 60 min, from 8.6 h up to 13.3 h, as well as the mean lag times in TSBYE. Modelling of the outgrowth kinetics comparing the two types of stress (oxidative vs acid) and the two systems of growth (colonial vs planktonic) revealed that low starting concentrations hindered the detection of viable L. monocytogenes cells, either due to VBNC induction or cell heterogeneity.

Diurnal pattern and characteristic of soil respiration and net ecosystem carbon exchange in alpine meadow ecosystem on the northeastern Qinghai-Tibet Plateau

Analyzing the diurnal pattern of soil respiration is essential for understanding the potential mechanisms of carbon cycle. Additionally, long-term and high temporal frequency soil respiration observations are crucial and valuable at different time scales, particularly in alpine regions. Therefore, it is critical to conduct research on the diurnal pattern of soil respiration in areas sensitive to global warming. Here, four group (including soil respiration, heterotrophic respiration, net ecosystem carbon exchange, and net ecosystem carbon exchange under warming condition) of experiments were designed with a total 12 chambers, and data collected during growing season in 2023 (April to September) obtained by automatic observation system at hour-scale and four-parameter Gaussian equation were used to investigate the diurnal pattern of soil respiration and net ecosystem carbon exchange in alpine meadow ecosystem on the northeastern Qinghai-Tibet Plateau. The results indicated that: 1) the soil temperature was crucial factor for the variations in diurnal pattern of soil respiration and net ecosystem carbon exchange in four experiments. The response of the heterotrophic components to the diurnal variation in soil temperature induced diurnal lag between soil respiration and soil temperature, with mean lag time of 1.7 h. 2) The diurnal peak time of net ecosystem carbon exchange was 1–3 h earlier than respiration, and the diurnal variation of soil tempiration was one of the main driving forces. 3) Additionally, warming advanced the diurnal peak time of net ecosystem carbon exchange by 1.2–2 h through explaining the parameters of the Gaussian function. It also promoted microbial resistance, thereby limiting the increase in soil respiration during nighttime. The study suggested that temperature varied soil microenvironment and biochemical processes in alpine meadow ecosystem, thus affecting the diurnal pattern. Indeed, this study focused solely on traditional factors, and further investigations were needed, particularly from a biotic perspective, to validate these conclusions.

The first involved joints and associated factors in patients with rheumatoid arthritis.

This study aimed to investigate the first involved joints and associated factors in Turkish patients with rheumatoid arthritis (RA). This retrospective cross-sectional study included 300 newly diagnosed and disease-modifying antirheumatic drug-naïve RA patients (240 females, 60 males; mean age: 54±1.2 years; range, 18 to 82 years). Baseline demographic, clinical, and laboratory data were evaluated between January 2022 and December 2022. The patients were divided into four groups according to autoantibody profile: antibody-negative patients (Group 1; both RF and anti-CCP were negative in this group of patients), RF-positive patients (Group 2), anti-CCP-positive patients (Group 3), and patients with dual seropositivity with RF and antiCCP (Group 4). The patients were also divided into two groups according to the size of the first affected joint: patients with SJI at diagnosis and patients without SJI involvement at diagnosis. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody positivity rates were 40.3% and 35.6%, respectively. The mean lag time to diagnosis was 25±36 months. At the disease onset, 20% of patients did not have small joint involvement (SJI). Seronegative patients tended to be female (p=0.001), had longer lag time (p=0.001), and had lower levels of C-reactive protein (p=0.025), white blood count (p=0.005), and neutrophil/lymphocyte ratio (p=0.001) compared to the dual seropositive group. Patients presenting with SJI had a younger age (p=0.002), tended to be female (p=0.001), and had lower RF (p=0.034) and anti-CCP (p=0.031) positivity. Only age (p=0.005) and dual seronegativity (RF and anti-CCP; p=0.035) were the independent predictors of SJI in multivariate analysis. The decreasing age and seronegative status were defined as independent risk factors of SJI at the onset of RA. Population-based, prospective studies are needed for earlier diagnosis.

Incidence of Acute Kidney Injury in 1 - 14 years old Critically ill Children in a Tertiary care Center

Introduction:Acute Kidney injury (AKI) is associated with poor outcomes in critically ill hospitalized children. There are very few studies on incidence of AKI based on urine output criteria of KDIGO (Kidney Disease: Improving Global Outcome) and time lag between the fall in urine output and rise in serum creatinine. This study was therefore aimed at determining the same.
 Methods: A prospective study was conducted in the Department of Paediatrics of a tertiary care hospital. 171 critically ill children between one to 14 years who were admitted in PICU were enrolled. Hourly urine output and eight hourly serum creatinine levels were measured and incidence of AKI was calculated along with lag time between fall in urine output and rise in serum creatinine. Outcome of children with AKI was also studied. Data analysis was done using SPSS software version 25.0 and Microsoft excel 2007.
 Results: The mean age + SD of children in the study was 5.5 years ± 3.76 with a range of one to 14 years, with 62.6 % of them being boys. The incidence of AKI in the study population was 14.62%. The mean lag time between fall in urine output and rise in serum creatinine was found to be 13.21 hours. AKI had a significant association with mortality, use of nephrotoxic drugs, inotropes and mechanical ventilation.
 Conclusions: A significant number of critically ill children develop AKI and its occurrence portends a poor outcome. Utilization of the KDIGO reduced urine output criteria as a marker of AKI allows for early detection and intervention

Impact of lag time on lung function impairment in pulmonary tuberculosis sequelae patients – A cross-sectional study

Background: Treatment completed pulmonary tuberculosis (PTB) patients are often left with permanent pulmonary function impairment. Lag time remains a major factor in determining the severity of the sequelae. Aims and Objectives: This study aims to assess the impact of lag time on PTB sequelae. Materials and Methods: A cross-sectional study was conducted during July 2019–December 2020. A total of 85 patients presenting with clinicoradiological features of PTB sequelae were recruited for the study and spirometry and diffusion capacity of lungs (DLCO) were done. They were divided into study groups based on lag time. The lag time (in days) was considered as primary explanatory variable. One-way ANOVA and Chi-square tests were used. coGuide V.1.0 was used for statistical analysis. Results: The mean lag time was 52.94 days in the study population. The mean duration of after treatment was 15.45 years in the study population. There was a statistically significant difference across study groups (classified based on the lag time) in lung function such as FVC%, FEV1, FEVI/FVC, MEF, DLCO, and duration of after treatment (P<0.05). Conclusion: The lag time from the development of symptom to the diagnosis of the disease has a significant impact on lung function impairment in PTB sequelae patients since the increase in lag time increases the severity of lung function impairment. Early identification and treatment may help in reducing the progression of lung function impairment.

The journey of patients with psoriasis and psoriatic arthritis

IntroductionTo describe the journey of patients with psoriatic arthritis (PsA), and psoriasis (PsO) with special emphasis on diagnosis and treatment delays. Materials and methodsAll patients with PsA registered between 2000 and 2016 were included. Mean lag time between first musculoskeletal symptom and diagnosis of PsA, between first musculoskeletal symptom and first physician encounter, mean lag time to first DMARD and mean lag time between PsO diagnosis and PsA diagnosis were calculated. Descriptive statistics are reported. Variables associated with a delay in PsA diagnosis >1 year were analyzed in multivariable analysis. ResultsOne hundred and eighty nine patients were included (139 PsA and 50 PsO), mean age 60.8 years (SD: 16.3), 57% were males. Mean lag time between first musculoskeletal symptom and diagnosis of PsA was 1.9 (SD: 4.7) years. In 90 patients (97%), the diagnosis of PsO preceded the diagnosis of PsA, a mean time of 14.3 years (SD: 13.9). Forty-nine patients (35%) had a delay of PsA diagnosis ≥1 year. Of the PsA patients, 84.7% received cDMARDs as first line therapy. The mean lag time between PsA diagnosis and initiation of DMARDs was 2 years (SD: 7.6). In logistic regression analysis no variable was independently associated with a delay equal or greater than 1 year in PsA diagnosis. ConclusionsA significant delay in consultation and diagnosis of PsA was evident in this single center study in a third of patients. None of the variables studied was associated with a delay in diagnosis greater than one year.

Effectiveness of mRNA and inactivated COVID-19 vaccines: A test-negative study in an infection-naïve Hong Kong population

Assess real-world effectiveness of vaccines against COVID-19. A test-negative study was conducted in January-May 2022 during an Omicron BA.2 wave in Hong Kong. COVID-19 was identified by RT-PCR. 1 to 1 case-control matching was based on propensity score with vaccine effectiveness adjusted for confounders. Altogether, 1781 cases and 1737 controls aged 3-105 years were analysed. The mean lag time from the last dose of vaccination to testing for SARS-CoV-2 was 133.9 (SD: 84.4) days. Two doses of either vaccine within 180 days offered a low effectiveness against COVID-19 of all severity combined (VEadj [95% CI] for BNT162b2: 27.0% [4.2 to 44.5], CoronaVac: 22.9% [1.3 to 39.7]), and further decreased after 180 days. Two doses of CoronaVac was poorly protective 39.5% [4.9 to 62.5] against severe diseases for age ≥60 years, but the effectiveness increased substantially after the third dose (79.1% [25.7 to 96.7]). Two doses of BNT162b2 protected age ≥60 years against severe diseases (79.3% [47.2, 93.9]); however, the uptake was not high enough to assess three doses. The current real-world analysis indicates a high vaccine effectiveness of three doses of inactivated virus (CoronaVac) vaccines against Omicron variant, whereas the effectiveness of two doses is suboptimal.

The journey of patients with psoriasis and psoriatic arthritis

IntroductionTo describe the journey of patients with psoriatic arthritis (PsA), and psoriasis (PsO) with special emphasis on diagnosis and treatment delays. Materials and methodsAll patients with PsA registered between 2000 and 2016 were included. Mean lag time between first musculoskeletal symptom and diagnosis of PsA, between first musculoskeletal symptom and first physician encounter, mean lag time to first DMARD and mean lag time between PsO diagnosis and PsA diagnosis were calculated. Descriptive statistics are reported. Variables associated with a delay in PsA diagnosis >1 year were analyzed in multivariable analysis. ResultsOne hundred and eighty nine patients were included (139 PsA and 50 PsO), mean age 60.8 years (SD: 16.3), 57% were males. Mean lag time between first musculoskeletal symptom and diagnosis of PsA was 1.9 (SD: 4.7) years. In 90 patients (97%), the diagnosis of PsO preceded the diagnosis of PsA, a mean time of 14.3 years (SD: 13.9). Forty-nine patients (35%) had a delay of PsA diagnosis ≥1 year. Of the PsA patients, 84.7% received cDMARDs as first line therapy. The mean lag time between PsA diagnosis and initiation of DMARDs was 2 years (SD: 7.6). In logistic regression analysis no variable was independently associated with a delay equal or greater than 1 year in PsA diagnosis. ConclusionsA significant delay in consultation and diagnosis of PsA was evident in this single center study in a third of patients. None of the variables studied was associated with a delay in diagnosis greater than one year.

PET/CT Fluoroscopy during PET/CT-Guided Interventions: Initial Experience

This study assessed the feasibility and functionality of the use of a high-speed image fusion technology to generate and display positron emission tomography (PET)/computed tomography (CT) fluoroscopic images during PET/CT-guided tumor ablation procedures. Thirteen patients underwent 14 PET/CT-guided ablations for the treatment of 20 tumors. A Food and Drug Administration–cleared multimodal image fusion platform received images pushed from a scanner, followed by near–real-time, nonrigid image registration. The most recent intraprocedural PET dataset was fused to each single-rotation CT fluoroscopy dataset as it arrived, and the fused images were displayed on an in-room monitor. PET/CT fluoroscopic images were generated and displayed in all procedures and enabled more confident targeting in 3 procedures. The mean lag time from CT fluoroscopic image acquisition to the in-room display of the fused PET/CT fluoroscopic image was 21 seconds ± 8. The registration accuracy was visually satisfactory in 13 of 14 procedures. In conclusion, PET/CT fluoroscopy was feasible and may have the potential to facilitate PET/CT-guided procedures.

Faith development as change in religious types: Results from three-wave longitudinal data with faith development interviews.

Faith, as a way of how people understand God and the world and make or discover meaning in their life, is characterized by individual differences and changes over the lifetime. Our research investigates these changes over the life span in terms of hierarchically ordered types that are the elements in our developmental model, which is a critical advancement and modification of Fowler’s theory of faith development. This study is the first to investigate whether there is development in faith over the adult life span and to identify predictors of developmental change. Our mixed-method design used three-wave longitudinal data (mean lag time 10.47 years from Wave 1 to Wave 3). A sample of N = 75 participants were interviewed with the faith development interview three times and each time answered comprehensive questionnaires. Results evidenced faith development over the life span: a majority in our data moved to a higher type, while change to a lower type did occur. Openness to experience and the religious schema truth of text and teachings were potential antecedents for faith development. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Modeling Lake Recovery Lag Times Following Influent Phosphorus Loading Reduction.

Internal feedback of nutrients may impede timely improvement in lake water quality. We describe a parsimonious, mechanistic framework for modeling lag times to recovery of phosphorus-enriched lakes, given decreases in external loading. The approach assumes first-order kinetics in a two-compartment system taking account of phosphorus storage in and loading from benthic sediments. Bayesian parameter modeling, published sediment phosphorus release rates, and a prior dynamic calibration for one lake are used to derive estimates of key parameters. Applications are developed for an example lake, as are maps displaying estimated times to attainment of a phosphorus criterion in lakes across a midwestern state, and lag time estimates for fractional water column concentration decrease averaged over HUC-8s. Mean lag times to 50 and 75% declines in water column phosphorus concentration were estimated as 13.1 and 39.0 years respectively, across more than 70,000 lentic water bodies in the continental United States.

Diencephalic syndrome-like presentation of brainstem tumor: a series case-based review.

Russel described a rare clinical entity known as diencephalic syndrome (DS) in 1951, which was traditionally caused by a neoplasm in the hypothalamic-optic chiasmatic region. DS is characterized by severe emaciation despite adequate or slightly reduced caloric intake, locomotor hyperactivity, euphoria and other minor features. Current evidence suggests that a rare population of children with a similar phenotype may have their tumor located in the posterior fossa instead, defining the DS-like presentation, a rare entity with few cases reported in the literature. A thorough search of three databases (PubMed, Ovid Medline, and Ovid Embase) was conducted to identify relevant papers reporting children with DS associated with brainstem tumors. To our knowledge, only seven cases have been documented in the literature. Moreover, we present four of our own cases, focusing on the unusual clinical presentation, the diagnosis process, and the lag time between the initial symptoms and the definitive diagnosis. In this review, the mean lag time between the onset of symptoms and diagnosis was 20.9months (median: 16months; range: 1.5-72months), whereas in our series of cases, the time was 32.5months (median: 33months; range: 7-57months). Despite recent significant advances in neuro-oncology diagnostic tools, this mean lag time did not improve when compared with the previous literature review from 1976. Throughout these data, we aim to raise awareness in the hopes of detecting intracranial neoplasms earlier in cases of children with profound emaciation of unknown cause.

Delayed response of net primary productivity with climate change in the Yiluo River basin

Climatic factors are the main drivers that change net primary productivity (NPP). We chose the Yiluo River Basin as the study area to investigate the response of NPP to climatic factors in the Yellow River’s middle reaches. The temporal and spatial distribution of net primary productivity and the trend change of slope in the basin from 2000 to 2020 are analyzed. In addition, we analyzed the correlation between the NPP and climatic factors (precipitation and temperature) and the time-lag effect. The results show that 1) the annual average NPP in the basin is 556.4 gC/m2/a, the maximum value that occurred in 2019. Most of the NPP’s mutation points in the basin’s forest appeared in 2004, while the NPP’s mutation points in arable land mostly appeared in 2008 and 2009. 2) The slope trend analysis result of NPP from 2000 to 2020 shows that the NPP in 67.88% of the basin shows a significant increasing trend, 3.8% of the basin shows a significant decrease, and the other area show no significant change. 3) The correlation analysis between NPP and climatic factors shows a positive correlation between precipitation and NPP in 62.3% of the basin and a positive correlation between air temperature and NPP in 62.5%. The response of NPP to precipitation and temperature in the basin has different degrees of a time-lag effect. The NPP has a time-lag effect on precipitation in 44.8% of the basin, and its mean lag time is 8 days. NPP has a time-lag effect on temperature in 55.7% of the basin, and its mean lag time is 1 day. This study is beneficial to understanding the influence of climatic factor change on vegetation activities in the Yiluo River Basin. Our study illustrates the significance of time lag in analyzing the relationship between NPP and climatic factors. Furthermore, it provides support for scientific vegetation regulation and allocation, as well as adaptation to climate change in areas similar to the Loess Plateau, based on the lag time distribution corresponding to different vegetation types in different regions of the Yiluo River Basin. After that, these areas’ water resources will be fully utilized by vegetation, and ecological restoration could be accelerated.

An Automatic Foot and Shank IMU Synchronization Algorithm: Proof-of-concept.

When using wearable sensors for measurement and analysis of human performance, it is often necessary to integrate and synchronise data from separate sensor systems. This paper describes a synchronization technique between IMUs attached to the shanks and insoles attached at the feet and aims to solve the need to compute the ankle joint angle, which relies on synchronized sensor data. This will additionally enable concurrent analysis using gait kinematic and kinetic features. A proof-of-concept of the algorithm, which relies on cross-correlation of gyroscope sensor data from the shank and foot, to align the sensor systems is demonstrated. The algorithm output is validated against those signals synchronized using manually annotated heel-strike and toe-off ground-truth signal landmarks, identified in both the shank and feet signals using previously published definitions. Results demonstrate that the developed algorithm is capable of synchronizing both sensor systems, based on IMU data from both healthy participants and participants suffering from knee osteoarthritis, with a mean lag time bias of 25.56ms when compared to the ground truth. A proof-of-concept of technique to synchronise IMUs attached to the shanks and insoles attached at the feet is demonstrated and offers an alternative approach to sensor system synchronisation.

Temperature-dependent self-assembly of biofilaments during red blood cell sickling.

Molecular self-assembly plays a vital role in various biological functions. However, when aberrant molecules self-assemble to form large aggregates, it can give rise to various diseases. For example, sickle cell disease and Alzheimer's disease are caused by self-assembled hemoglobin fibers and amyloid plaques, respectively. Here, we study the assembly kinetics of such fibers using kinetic Monte Carlo simulation. We focus on the initial lag time of these highly stochastic processes, during which self-assembly is very slow. The lag time distributions turn out to be similar for two very different regimes of polymerization, namely, (a) when polymerization is slow and depolymerization is fast and (b) the opposite case, when polymerization is fast and depolymerization is slow. Using temperature-dependent on- and off-rates for hemoglobin fiber growth, reported in recent in vitro experiments, we show that the mean lag time can exhibit non-monotonic behavior with respect to the change in temperature.

Malignant Transformation of Giant Cell Tumor of Bone and the Association with Denosumab Treatment: A Radiology and Pathology Perspective.

Objective Malignancy in giant cell tumor of bone (mGCTB) is categorized as primary (concomitantly with conventional GCTB) or secondary (after radiotherapy or other treatment). Denosumab therapy has been suggested to play a role in the etiology of secondary mGCTB. In this case series from a tertiary referral sarcoma center, we aimed to find distinctive features for malignant transformation in GCTB on different imaging modalities. Furthermore, we assessed the duration of denosumab treatment and lag time to the development of malignancy. Methods From a histopathology database search, 6 patients were pathologically confirmed as having initial conventional GCTB and subsequently with secondary mGCTB. Results At the time of mGCTB diagnosis, 2 cases were treated with denosumab only, 2 with denosumab and surgery, 1 with multiple curettages and radiotherapy, and 1 with surgery only. In the 4 denosumab treated patients, the mean lag time to malignant transformation was 7 months (range 2–11 months). Imaging findings suspicious of malignant transformation related to denosumab therapy are the absence of fibro-osseous matrix formation and absent neocortex formation on CT, and stable or even increased size of the soft tissue component. Conclusion In 4 patients treated with denosumab, secondary mGCTB occurred within the first year after initiation of treatment. Radiotherapy-associated mGCTB has a longer lag time than denosumab-associated mGCTB. Close clinical and imaging follow-up during the first months of denosumab therapy is key, as mGCTB tends to have rapid aggressive behavior, similar to other high-grade sarcomas. Nonresponders should be (re) evaluated for their primary diagnosis of conventional GCTB.

Retinoblastoma in Calabar Nigeria: An 18-Month Retrospective Review of Clinical Presentation at a Tertiary Eye Center

Background: Retinoblastoma, although rare, is the most frequently occurring primary intraocular tumor of childhood. While a cure is often achieved where appropriate treatment is instituted early in the disease, late presentation often leads to unsuccessful treatment interventions. Aim: The aim of this study is to provide baseline information on the clinical presentation of retinoblastoma as seen in a tertiary pediatric eye care facility in Calabar, Nigeria. Materials and Methods: A retrospective review of case files of children presenting to the Calabar Children's Eye Center (CCEC) with retinoblastoma over 18 months from January 1, 2018 to June 30, 2019 was done. Results: Data were collected from 39 children with retinoblastoma who met the inclusion criteria. There were 22 (56.4%) males and 17 (43.6%) females, and the age range was 7–41 months, with a mean age of 25.6 (±9.0) months. Unilateral disease was seen in 27 (69.2%) participants, whereas 12 (30.8%) had bilateral disease. Although multiple symptoms were seen in many participants protrusion of eye was the most frequently occurring first symptom, (17, 44.0%) followed by red eye (13, 33.0%), whitespot in eye (5, 13.0%), and abnormal alignment (4, 10.0%) among study participants. The lag time from recognition of symptoms to initial consultation ranged from 1 to 25 months, with a mean lag time of 9.13 ± 5.68 months. The ICRB classification system was most frequently used, 27 (69.2%), followed by cTNMH 11 (28.2%), and International Intraocular Retinoblastoma Classification 1 (2.6%). The International Retinoblastoma Staging System was representative. Of the 78 eyes studied, (51, 65.3%) had different stages of retinoblastoma with the majority presenting as advanced retinoblastoma (46, 90.2%). Conclusions: Retinoblastoma is seen at the CCEC. Although the most frequent symptom was protrusion of eye, the lag time was often several months long. Most patients presented late with advanced ocular retinoblastoma and or extraocular disease.

Increased histone-DNA complexes and endothelial-dependent thrombin generation in severe COVID-19

Coagulopathy in severe COVID-19 is common but poorly understood. The purpose of this study was to determine how SARS-CoV-2 infection impacts histone levels, fibrin structure, and endogenous thrombin potential in the presence and absence of endothelial cells. We studied individuals with SARS-CoV-2 infection and acute respiratory distress syndrome at the time of initiation of mechanical ventilation compared to healthy controls. Circulating histone-DNA complexes were elevated in the plasma of COVID-19 patients relative to healthy controls (n=6, each group). Using calibrated automated thrombography, thrombin generation was altered in COVID-19 patient plasma samples. Despite having increased endogenous thrombin potential, patient plasma samples exhibited prolonged lag times and times to peak thrombin in the presence of added tissue factor and PCPS. Strikingly different results were observed when endothelial cells were used in place of tissue factor and PCPS. While healthy control plasma samples did not generate measurable thrombin after 60 min, plasma samples from COVID-19+ patients formed thrombin (mean lag time ~20 min). Consistent with the observed alterations in thrombin generation, clots from COVID-19 subjects exhibited a denser fibrin network, thinner fibers and lower fibrin resolvability. Elevated histones, aberrant fibrin formation, and increased endothelial-dependent thrombin generation may contribute to coagulopathy in COVID-19.

The implications of lag times between nitrate leaching losses and riverine loads for water quality policy

Understanding the lag time between land management and impacts on riverine nitrate–nitrogen (N) loads is critical to understand when action to mitigate nitrate–N leaching losses from the soil profile may start improving water quality. These lags occur due to leaching of nitrate–N through the subsurface (soil and groundwater). Actions to mitigate nitrate–N losses have been mandated in New Zealand policy to start showing improvements in water quality within five years. We estimated annual rates of nitrate–N leaching and annual nitrate–N loads for 77 river catchments from 1990 to 2018. Lag times between these losses and riverine loads were determined for 34 catchments but could not be determined in other catchments because they exhibited little change in nitrate–N leaching losses or loads. Lag times varied from 1 to 12 years according to factors like catchment size (Strahler stream order and altitude) and slope. For eight catchments where additional isotope and modelling data were available, the mean transit time for surface water at baseflow to pass through the catchment was on average 2.1 years less than, and never greater than, the mean lag time for nitrate–N, inferring our lag time estimates were robust. The median lag time for nitrate–N across the 34 catchments was 4.5 years, meaning that nearly half of these catchments wouldn’t exhibit decreases in nitrate–N because of practice change within the five years outlined in policy.