COVID-19 hospitalization rates rise exponentially with age,inversely proportional to thymic T-cell production

Here, we report that COVID-19 hospitalization rates follow an exponential relationship with age, doubling for every 16 years of age or equivalently increasing by 4.5% per year of life (R² = 0.98). This mirrors the well-studied exponential decline of both thymus volume and T-cell production, which halve every 16 years. COVID-19 can therefore be added to the list of other diseases with this property, including those caused by methicillin-resistant Staphylococcus aureus, MERS-CoV, West Nile virus, Streptococcus pneumoniae and certain cancers, such as chronic myeloid leukaemia and brain cancers. In addition, the incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. Since these properties are shared with some non-contagious diseases, we hypothesized that the age dependence does not come from social-mixing patterns, i.e. that the probability of hospitalization given infection rises exponentially, doubling every 16 years. A Bayesian analysis of daily hospitalizations, incorporating contact matrices, found that this relationship holds for every age group except for the under 20s. While older adults have fewer contacts than young adults, our analysis suggests that there is an approximate cancellation between the effects of fewer contacts for the elderly and higher infectiousness due to a higher probability of developing severe disease. Our model fitting suggests under 20s have 49–75% additional immune protection beyond that predicted by strong thymus function alone, consistent with increased juvenile cross-immunity from other viruses. We found no evidence for differences between age groups in susceptibility to infection or infectiousness to others (given disease state), i.e. the only important factor in the age dependence of hospitalization rates is the probability of hospitalization given infection. These findings suggest the existence of a T-cell exhaustion threshold, proportional to thymic output and that clonal expansion of peripheral T-cells does not affect disease risk. The strikingly simple inverse relationship between risk and thymic T-cell output adds to the evidence that thymic involution is an important factor in the decline of the immune system with age and may also be an important clue in understanding disease progression, not just for COVID-19 but other diseases as well.     

Project to develop school education services in Delhi, India

There are many ways in which quantitative decision models can be applied in project management. The introduction of a project evaluation review technique network model to the development of a school education service in the city of Delhi, India, is described. The reasons for choosing this method, its advantages and limitations are discussed. Examples of the information obtained from the model are presented and explained.     

Coupled-mode theory of overmoded cylindrical metal bragg-reflectors

A coupled-mode theory of overmoded, cylindrical metal Bragg-reflectors is presented. The first-order Bragg coupling constants are derived for TE → TE, TM → TM, TE → TM, and TM → TE mode conversions. Reflectivities and transverse modeQ-factors are computed for a Bragg-reflector resonator. The results illustrate important competition effects between nearly-degenerate-transverse-modes occurring within both the Bragg-reflectors and the resonator.     

Longitudinal bone mineral density changes in early rheumatoid arthritis

A prospective longitudinal study of patients with early RA was performed to examine the influence of disease duration, disease activity and physical activity on bone loss. Sixty-seven patients with non-steroid treated RA of less than 5 yr duration, including 16 patients with disease duration less than 6 months, had BMD measurements of the femoral neck and the lumbar spine over a 12-month period using dual energy X-ray absorptiometry. The BMD changes were compared with values from 72 control patients and were also correlated with serial measurements of disease activity (measured by the Stoke Index) and disability [measured by the Health Assessment Questionnaire (HAQ) score], at 3-monthly intervals over the 12-month period. No significant differences in BMD changes were found between RA patients and controls overall. Patients with disease duration of less than 6 months had significantly greater loss of BMD at the femoral neck (-3.9%, S.E.M. 1.5) than the remainder of the cohort (-0.2%, S.E.M. 0.7) (P = 0.02) and controls (-0.8%, S.E.M. 0.6). Lumbar spine BMD changes correlated with the initial Stoke Index (Rs-0.373, P = 0.01) but not mean Stoke Indices. There was no correlation of BMD changes with age or HAQ scores. These findings suggest that significant bone loss occurs within the first few months of disease in patients with RA.     

Transrectal electrostimulation therapy for neuropathic bowel dysfunction in children with myelomeningocele

PURPOSE: We attempted to evaluate the efficacy of transrectal bowel stimulation for neurogenic bowel dysfunction in children with myelodysplasia. MATERIALS AND METHODS: Daily sessions of transrectal electrostimulation were performed on an outpatient basis for 2 to 3 weeks on children with myelodysplasia and stool incontinence. If benefits were noted, 5 to 10 additional daily sessions were performed. Complete success was defined as improvement in all parameters of interest, including decrease in the frequency of daily bowel movements, increased sensation, increased ability to hold stool and a significant subjective change in bowel habits. Moderate success implied improvement in 1 to 3 parameters and treatment failure was defined as lack of improvement in any parameter. RESULTS: A total of 55 children 2 to 14 years old (mean age 6.7) completed a mean of 18 daily sessions per patient of bowel electrostimulation. Followup ranged from 1 to 6 years. Diapers are no longer required due to defecation problems in 14 children older than 3 years. Complete success was achieved in 20 cases (36.3%) and moderate success in an additional 30 (54.5%, overall success rate 90.8%). Specifically, 89% of the patients reported elimination of stooling accidents, 82% reported increased sensation and 71% were able to hold the bowel movement. Overall 68% of the patients noticed significantly improved bowel function. Complete/moderate success of transrectal electro-stimulation was statistically significant for all 4 parameters (p < 0.05), and complete success was significant for increased sensation, ability to hold and episodes of accidents. Therapy failed in 5 children (9%). There were no untoward effects. CONCLUSIONS: Transrectal electrostimulation is a well tolerated and minimally invasive modality that provides sustainable improvement in stool continence in children with myelomeningocele and neuropathic bowel dysfunction.     

A case-mix classification system for medical rehabilitation

Dissatisfaction with Medicare's current system of paying for rehabilitation care has led to proposals for a rehabilitation prospective payment system, but first a classification system for rehabilitation patients must be created. Data for 36,980 patients admitted to and discharged from 125 rehabilitation facilities between January 1, 1990, and April 19, 1991, were provided by the Uniform Data System for Medical Rehabilitation. Classification rules were formed using clinical judgment and a recursive partitioning algorithm. The Functional Independence Measure version of the Function Related Groups (FIM-FRGs) uses four predictor variables: diagnosis leading to disability, admission scores for motor and cognitive functional status subscales as measured by the Functional Independence Measure, and patient age. The system contains 53 FRGs and explains 31.3% of the variance in the natural logarithm length of stay for patients in a validation sample. The FIM-FRG classification system is conceptually simple and stable when tested on a validation sample. The classification system contains a manageable number of groups, and may represent a solution to the problem of classifying medical rehabilitation patients for payment, facility planning, and research on the outcomes, quality, and cost of rehabilitation.     

Vitek system antimicrobial susceptibility testing of O1, O139, and non-O1 Vibrio cholerae

Vibrio cholerae causes epidemic diarrhea throughout the world. Fluid replacement is the primary therapy for cholera; however, high mortality rates often necessitate the use of antibiotics. V. cholerae, like most bacteria, has developed resistance to some antibiotics. In the early 1990s a new serotype strain, Bengal 0139, began a new wave of cholera epidemics. Bengal isolates showed unique trends in antimicrobial resistance. Many clinical laboratories use automated antibiotic susceptibility testing for V. cholerae. It is important to know if automated susceptibility test results for V. cholerae coincide with reported trends in antibiotic susceptibility. In the present study, we used the Vitek automated susceptibility system to determine the susceptibilities of 79 V. cholerae O1 isolates, 100 O139 isolates, and 112 non-O1 isolates. Vitek susceptibilities for V. cholerae showed a good correlation with preestablished epidemiological data. Although the new O139 serogroup showed a trend of increased resistance to trimethoprim-sulfamethoxazole and nitrofurantoin, it was more susceptible to ampicillin than previous serogroup O1 and non-O1 strains. Regardless of serogroup, > or = 98% of the V. cholerae isolates tested were susceptible to most antibiotics tested by us. It is important to continue susceptibility testing of all new isolates of V. cholerae because of emerging resistant strains. However, V. cholerae remains susceptible to most of the available antibiotics.     

The relative contribution of selected carpal bones to global wrist motion during simulated planar and out-of-plane wrist motion

The present study assesses the endocrinological, endometrial histology and vaginal ultrasound profiles of nomegestrol acetate subdermal implant users at varying times after insertion. Follicle stimulatory hormone, luteinizing hormone, oestradiol, progesterone, vaginal ultrasound assessment of the ovaries and the histological dating of the endometrium were serially assessed for a period of 50 days immediately after the insertion, and after at 6 months and 12 months of use. The endocrinological results of this prospective observational clinical trial indicated that 75% of the cycles across the study period in Uniplant users were anovulatory, 63% showing development of a persistent non-luteinized follicle. Anovulatory cycles devoid of follicular development were seen primarily in the first months after Uniplant insertion. Ovulatory cycles represented 25% of the Uniplant cycles. Inadequate luteal phase or disregulation of follicular growth was a common feature of ovulatory cycles. In conclusion, these findings suggest that the contraceptive mechanisms of a single nomegestrol acetate subdermal implant involve prevention of follicular growth, development of a persistent non-luteinized follicle, inadequate luteal phase and disruption of the endometrial architecture.