Pervasive Downward Bias in Estimates of Liability-Scale Heritability in Genome-wide Association Study Meta-analysis: A Simple Solution.

BACKGROUND: Single nucleotide polymorphism-based heritability is a fundamental quantity in the genetic analysis of complex traits. For case-control phenotypes, for which the continuous distribution of risk in the population is unobserved, observed-scale heritability estimates must be transformed to the more interpretable liability scale. This article describes how the field standard approach incorrectly performs the liability correction in that it does not appropriately account for variation in the proportion of cases across the cohorts comprising the meta-analysis. We propose a simple solution that incorporates cohort-specific ascertainment using the summation of effective sample sizes across cohorts. This solution is applied at the stage of single nucleotide polymorphism-based heritability estimation and does not require generating updated meta-analytic genome-wide association study summary statistics. METHODS: We began by performing a series of simulations to examine the ability of the standard approach and our proposed approach to recapture liability-scale heritability in the population. We went on to examine the differences in estimates obtained from these 2 approaches for real data for 12 major case-control genome-wide association studies of psychiatric and neurologic traits. RESULTS: We found that the field standard approach for performing the liability conversion can downwardly bias estimates by as much as approximately 50% in simulation and approximately 30% in real data. CONCLUSIONS: Prior estimates of liability-scale heritability for genome-wide association study meta-analysis may be drastically underestimated. To this end, we strongly recommend using our proposed approach of using the sum of effective sample sizes across contributing cohorts to obtain unbiased estimates.

Tetanus, analysis of 29 cases.

BACKGROUND: Tetanus disease is caused by Clostridium tetani, an anaerobe bacteria found in dust and soil. Once reached human body through damaged tissues, C. tetani releases several neurotoxins which block the inhibitory function, leading to an increased muscle tone, ultimately causing respiratory failure. Severe tetanus is a life-threatening disease, especially in low-income-regions. METHODS: This is a retrospective case-series study, undertaken at two hospitals of Vigo (population area 600,000 inhabitants). Tetanus cases were identified through the discharge databases of both hospitals between the years 1995-2019. Epidemiological and clinical data were obtained from the patient's medical records. RESULTS: A total of 33 cases were identified; median age was 67 years, and most of patients were women (n=16, 55.2%). Generalized tetanus was the most common clinical course, and neck stiffness was the most frequent symptom. A total of 25 patients (86%) were admitted to the Intensive Care Unit, 21 required invasive ventilation and 2 patients died. DISCUSSION: The incidence of tetanus was low but most of cases were severe. Mortality was slightly higher than previously reported. Interestingly, the deceased patients were old-women, consistent with previously reported research in high-income-regions, while mortality in low-income-countries concentrates in middle-aged men.

Chondroid Metaplasia in a Fibroepithelial Polyp of Gingiva.

Gingival masses are commonly encountered in clinical practice and can be a result of many conditions one of them could be metaplasia. Metaplasia is defined as the replacement of the lining of an organ with the type of lining normally found at another site. We are reporting a case of a 17-year-old Mexican male who presented with a pedunculated nodule associated to maxillary anterior gingiva. The histopatological examination revealed a chondroid material covered by stratified squamous epithelium and was diagnosed as chondroid metaplasia.

Utilidad de la ultrasonografía introital en incontinencia de orina de esfuerzo, curva ROC / Usefulness of introital ultrasonography in stress incontinence of urine, ROC curve

Para determinar si existe una variable en ultrasonografía introital que pueda utilizarse para distinguir mujeres con incontinencia de orina de esfuerzo (IOE) y mujeres continentes, realizamos este estudio de tipo diagnóstico prospectivo de un solo centro involucrando 24 mujeres continentes y 43 mujeres con IOE todas voluntarias seleccionadas según los criterios de inclusión- exclusión, se realizó ultrasonografía introital a todas ellas consignando diversos parámetros de distancias y ángulos en reposo durante Valsalva y Kegel, de todas las variables analizadas la altura H durante Valsalva fue la mejor para distinguir entre pacientes incontinentes y continentes siendo 15.5 mm el valor de corte según la curva de ROC correspondiente.

Objective: To determine if there is a variable on introital ultrasonography (IUS) that can be used to distinguish between women with stress urinary incontinence and continent women. Patients and methods: This single centre, prospective, diagnostic study, comprised 24 women continent and 43 incontinent who were all appropriately informed volunteers selected according to the inclusion criteria. IUS with a transvaginal probe was performed on all women; the measurement plane was standardized and coordinates were obtained at rest, on straining and Kegel. Several distances and angles were measured to determine if any provided an objective distinction between continent and incontinent women. Results: Among all the IUS variables assessed, the height H (the vertical distance from a horizontal line drawn at the lower border of the symphysis and the bladder neck) on straining (Valsalva) was the best for distinguishing continent and incontinent women. The receiver operating characteristic curves showed that with a threshold of 15,5 mm, the height H on straining had a sensitivity of 70.8 percent and a specificity of 82.9 percent for detecting Stress Urinary incontinence (SUI). The sliding (calculated as the difference between the height H at rest and under stress) and the height H at rest could also discriminate, but with lower significance. Conclusions: IUS is an important tool for diagnosing SUI; there are three independent variables, one dynamic (sliding) and two static (height H at rest and straining), that can be used to distinguish between continent women and those with SUI. The height H at Valsalva is the most reliable, as it has the highest sensitivity and specificity. We think that the simplicity, low financial cost and reliability of IUS could allow it to be a routine procedure for physicians working in incontinence units.