Functional and morphological studies of the primate outflow apparatus

The present investigation of the primate outflow apparatus comprises of two parts. Part I is concerned with the physiological and morphological effects of hyaluronidase on the outflow apparatus of the pig tailed macaque. Part II is a study of age-related changes in the human outflow apparatus. The aim of the first part of the investigation was to discover whether glycosaminoglycans in the trabecular meshwork, particularly the cribriform layer, contributed towards the resistance to aqueous outflow through this pathway. Nine pig tailed macaques (Macaca nemestrina) received an intracameral injection of 300 I.U. of testicular hyaluronidase (in 100 mul of Barany' s fluid) in one eye and the fellow eye served as a control, receiving Barany's fluid alone. One hour after the injections the flow rates at 18 mm Hg and 22 mm Hg from a perfusion system were determined in order to calculate outflow facility. The eyes were perfuse fixed in situ at 18 mm Hg, half an hour after the physiological determinations. Four eyes, two controls and two experimentals, were excluded from the study due to manipulative failures during the experiment. There was a great deal of variation in the results between animals. Despite this it was found that the flow rates in the hyaluronidase-treated eyes were significantly greater than the controls in three of five pairs at 18 mm Hg and in all five pairs at 22 mm Hg. Due to the variation between animals the group results did not prove to be statistically significant. There was no gross morphological difference between control and hyaluronidase-treated eyes, with the exception of slightly greater distension and fewer 'giant vacuoles' in the enzyme treated eyes. The outflow apparatus in both groups of eyes showed marked alterations in configuration compared with the normal unperfused tissue. These changes included rounding up of trabecular endothelial cells; disruption of the cribriform layer; "blow-outs" or focal ballooning of the lining endothelium of Schlemm's canal and herniation of cribriform tissue into collector channel openings. These changes were more severe than would have been predicted on the basis of pressure effects alone and may in fact have been due to physiological manipulation and over perfusion with mock aqueous. In Part II, a wide age range of human eyes, which had been immerse fixed after enucleation in the treatment of various ocular and orbital disorders of the posterior pole, were morphologically investigated. There was a great deal of variation in the morphological appearance of the outflow tissues not only between eyes of similar ages but also within one eye. Despite the variation, several age-related changes were qualitatively and quantitatively described. These included : the thickening of the trabeculae due to increased deposition of connective tissue elements; the trabeculae in older eyes often appeared denuded of their cell cover which seemed to cause focal degeneration and the release of connective tissue materials which appeared to accumulate in the outer meshwork; there was an increase with age in the electron dense plaques in the cribriform layer and a decrease in the ground substance; 'giant vacuoles' in the lining endothelium of Schlemm's canal were rare in older eyes (over 50 years); the incidence of localised canal closure due to apposition of the inner and outer walls was greater in older eyes. The present study of age-related changes in the human outflow apparatus will hopefully contribute to future morphological studies of the outflow apparatus from patients suffering from primary open angle glaucoma

Alpenloopings in Heimatklänge : Jodeln als Globalisierungsbewegung zwischen Tradition und Experiment

The subject of my contribution is the functioning and effect of yodeling as an experimental form of vocals and singing as presented in Stefan Schwieterts documentary Heimatklänge [Sounds of home] (CH/D 2007); a recursive figure that co-constitutes what is identified as home and forges a sense of identity. Yodeling enables two home »loops« of a special kind: first, the recursive calling-singing in the Swiss Alps, which returns to inside the body as a result of a specific geographic location and its echo, and second, a worldwide sounds network, which through the art of the three Swiss vocal artists Erika Stucky, Noldi Alder, and Christian Zehnder, forms an acoustic bridge from Switzerland via Mongolia to the USA. The essay follows the associative structure of the ilm, which describes a circular movement that seeks to locate the concept of home while alternating in sounds and images between region and global, own and alien, traditional and experimental. With its description of the hypothesis of the origin of yodeling the study begins with a musicological perspective; next, it present an in-depth film analysis of Heimatklänges presentation of yodeling; finally, it formulates a globalization hypothesis in the context of culture studies, which in conjunction with the film endeavours to rethink the relationship between mountain landscape and people

Where are we? : The anatomy of the murine cortical meninges revisited for intravital imaging, immunology, and clearance of waste from the brain

Rapid progress is being made in understanding the roles of the cerebral meninges in the maintenance of normal brain function, in immune surveillance, and as a site of disease. Most basic research on the meninges and the neural brain is now done on mice, major attractions being the availability of reporter mice with fluorescent cells, and of a huge range of antibodies useful for immunocytochemistry and the characterization of isolated cells. In addition, two-photon microscopy through the unperforated calvaria allows intravital imaging of the undisturbed meninges with sub-micron resolution. The anatomy of the dorsal meninges of the mouse (and, indeed, of all mammals) differs considerably from that shown in many published diagrams: over cortical convexities, the outer layer, the dura, is usually thicker than the inner layer, the leptomeninx, and both layers are richly vascularized and innervated, and communicate with the lymphatic system. A membrane barrier separates them and, in disease, inflammation can be localized to one layer or the other, so experimentalists must be able to identify the compartment they are studying. Here, we present current knowledge of the functional anatomy of the meninges, particularly as it appears in intravital imaging, and review their role as a gateway between the brain, blood, and lymphatics, drawing on information that is scattered among works on different pathologies

Relation of severe COVID-19 in Scotland to transmission-related factors and risk conditions eligible for shielding support:REACT-SCOT case-control study

Abstract Background Clinically vulnerable individuals have been advised to shield themselves during the COVID-19 epidemic. The objectives of this study were to investigate (1) the rate ratio of severe COVID-19 associated with eligibility for the shielding programme in Scotland across the first and second waves of the epidemic and (2) the relation of severe COVID-19 to transmission-related factors in those in shielding and the general population. Methods In a matched case-control design, all 178,578 diagnosed cases of COVID-19 in Scotland from 1 March 2020 to 18 February 2021 were matched for age, sex and primary care practice to 1,744,283 controls from the general population. This dataset (REACT-SCOT) was linked to the list of 212,702 individuals identified as eligible for shielding. Severe COVID-19 was defined as cases that entered critical care or were fatal. Rate ratios were estimated by conditional logistic regression. Results With those without risk conditions as reference category, the univariate rate ratio for severe COVID-19 was 3.21 (95% CI 3.01 to 3.41) in those with moderate risk conditions and 6.3 (95% CI 5.8 to 6.8) in those eligible for shielding. The highest rate was in solid organ transplant recipients: rate ratio 13.4 (95% CI 9.6 to 18.8). Risk of severe COVID-19 increased with the number of adults but decreased with the number of school-age children in the household. Severe COVID-19 was strongly associated with recent exposure to hospital (defined as 5 to 14 days before presentation date): rate ratio 12.3 (95% CI 11.5 to 13.2) overall. The population attributable risk fraction for recent exposure to hospital peaked at 50% in May 2020 and again at 65% in December 2020. Conclusions The effectiveness of shielding vulnerable individuals was limited by the inability to control transmission in hospital and from other adults in the household. Mitigating the impact of the epidemic requires control of nosocomial transmission

Effect of vaccination on transmission of SARS-CoV-2

No abstract available

Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study

Objective: Many healthcare staff work in high-risk settings for contracting and transmitting Severe Acute Respiratory Syndrome Coronavirus 2. Their risk of hospitalisation for coronavirus disease 2019 (COVID-19), and that of their households, is poorly understood. Design and settings and participants: During the peak period for COVID-19 infection in Scotland (1st March 2020 to 6th June 2020) we conducted a national record linkage study to compare the risk of COVID-19 hospitalisation among healthcare workers (age: 18-65 years), their households and other members of the general population. Main outcome: Hospitalisation with COVID-19 Results: The cohort comprised 158,445 healthcare workers, the majority being patient facing (90,733 / 158,445; 57.3%), and 229,905 household members. Of all COVID-19 hospitalisations in the working age population (18-65-year-old), 17.2% (360 / 2,097) were in healthcare workers or their households. Adjusting for age, sex, ethnicity, socio-economic deprivation and comorbidity, the risk of COVID-19 hospitalisation in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazards ratio [HR] 0.81; 95%CI 0.52-1.26 and 0.86; 95%CI 0.49-1.51 respectively). In models adjusting for the same covariates however, patient facing healthcare workers, compared to non-patient facing healthcare workers, were at higher risk (HR 3.30; 95%CI 2.13-5.13); so too were household members of patient facing healthcare workers (HR 1.79; 95%CI 1.10-2.91). On sub-dividing patient-facing healthcare workers into those who worked in front-door, intensive care and non-intensive care aerosol generating settings and other, those in front door roles were at higher risk (HR 2.09; 95%CI 1.49-2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of COVID-19 hospitalisation was less than 0.5% but was 1% and above in older men with comorbidity. Conclusions: Healthcare workers and their households contribute a sixth of hospitalised COVID-19 cases. Whilst the absolute risk of hospitalisation was low overall, patient facing healthcare workers and their households had 3- and 2-fold increased risks of COVID-19 hospitalisation

Rapid Epidemiological Analysis of Comorbidities and Treatments as risk factors for COVID-19 in Scotland (REACT-SCOT): a population-based case-control study

Background The objectives of this study were to identify risk factors for severe coronavirus disease 2019 (COVID-19) and to lay the basis for risk stratification based on demographic data and health records. Methods and findings The design was a matched case-control study. Severe COVID-19 was defined as either a positive nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the national database followed by entry to a critical care unit or death within 28 days or a death certificate with COVID-19 as underlying cause. Up to 10 controls per case matched for sex, age, and primary care practice were selected from the national population register. For this analysis—based on ascertainment of positive test results up to 6 June 2020, entry to critical care up to 14 June 2020, and deaths registered up to 14 June 2020—there were 36,948 controls and 4,272 cases, of which 1,894 (44%) were care home residents. All diagnostic codes from the past 5 years of hospitalisation records and all drug codes from prescriptions dispensed during the past 240 days were extracted. Rate ratios for severe COVID-19 were estimated by conditional logistic regression. In a logistic regression using the age-sex distribution of the national population, the odds ratios for severe disease were 2.87 for a 10-year increase in age and 1.63 for male sex. In the case-control analysis, the strongest risk factor was residence in a care home, with rate ratio 21.4 (95% CI 19.1–23.9, p = 8 × 10−644). Univariate rate ratios for conditions listed by public health agencies as conferring high risk were 2.75 (95% CI 1.96–3.88, p = 6 × 10−9) for type 1 diabetes, 1.60 (95% CI 1.48–1.74, p = 8 × 10−30) for type 2 diabetes, 1.49 (95% CI 1.37–1.61, p = 3 × 10−21) for ischemic heart disease, 2.23 (95% CI 2.08–2.39, p = 4 × 10−109) for other heart disease, 1.96 (95% CI 1.83–2.10, p = 2 × 10−78) for chronic lower respiratory tract disease, 4.06 (95% CI 3.15–5.23, p = 3 × 10−27) for chronic kidney disease, 5.4 (95% CI 4.9–5.8, p = 1 × 10−354) for neurological disease, 3.61 (95% CI 2.60–5.00, p = 2 × 10−14) for chronic liver disease, and 2.66 (95% CI 1.86–3.79, p = 7 × 10−8) for immune deficiency or suppression. Seventy-eight percent of cases and 52% of controls had at least one listed condition (51% of cases and 11% of controls under age 40). Severe disease was associated with encashment of at least one prescription in the past 9 months and with at least one hospital admission in the past 5 years (rate ratios 3.10 [95% CI 2.59–3.71] and 2.75 [95% CI 2.53–2.99], respectively) even after adjusting for the listed conditions. In those without listed conditions, significant associations with severe disease were seen across many hospital diagnoses and drug categories. Age and sex provided 2.58 bits of information for discrimination. A model based on demographic variables, listed conditions, hospital diagnoses, and prescriptions provided an additional 1.07 bits (C-statistic 0.804). A limitation of this study is that records from primary care were not available. Conclusions We have shown that, along with older age and male sex, severe COVID-19 is strongly associated with past medical history across all age groups. Many comorbidities beyond the risk conditions designated by public health agencies contribute to this. A risk classifier that uses all the information available in health records, rather than only a limited set of conditions, will more accurately discriminate between low-risk and high-risk individuals who may require shielding until the epidemic is over