Severity of COVID-19 after Vaccination among Hemodialysis Patients: An Observational Cohort Study

Background and objectives: Patients receiving hemodialysis are at high risk from coronavirus disease 2019 (COVID-19) and demonstrate impaired immune responses to vaccines. There have been several descriptions of their immunologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but few studies have described the clinical efficacy of vaccination in patients on hemodialysis. // Design, setting, participants, & measurements: In a multicenter observational study of the London hemodialysis population undergoing surveillance PCR testing during the period of vaccine rollout with BNT162b2 and AZD1222, all of those positive for SARS-CoV-2 were identified. Clinical outcomes were analyzed according to predictor variables, including vaccination status, using a mixed effects logistic regression model. Risk of infection was analyzed in a subgroup of the base population using a Cox proportional hazards model with vaccination status as a time-varying covariate. // Results: SARS-CoV-2 infection was identified in 1323 patients of different ethnicities (Asian/other, 30%; Black, 38%; and White, 32%), including 1047 (79%) unvaccinated, 86 (7%) after first-dose vaccination, and 190 (14%) after second-dose vaccination. The majority of patients had a mild course; however, 515 (39%) were hospitalized, and 172 (13%) died. Older age, diabetes, and immune suppression were associated with greater illness severity. In regression models adjusted for age, comorbidity, and time period, prior two-dose vaccination was associated with a 75% (95% confidence interval, 56 to 86) lower risk of admission and 88% (95% confidence interval, 70 to 95) fewer deaths compared with unvaccinated patients. No loss of protection was seen in patients over 65 years or with increasing time since vaccination, and no difference was seen between vaccine types. // Conclusions: These data demonstrate a substantially lower risk of severe COVID-19 after vaccination in patients on dialysis who become infected with SARS-CoV-2

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

The Most Common Comorbidities in Dandy-Walker Syndrome Patients: A Systematic Review of Case Reports.

OBJECTIVE: Dandy-Walker syndrome (DWS) is a rare neurologic multi-entity malformation. This review aimed at reporting its main nonneurologic comorbidities. METHODS: Following PRISMA guidelines, search in Medline was conducted (2000-2014, keyword: dandy-walker). Age, sex, country, DWS type, consanguinity or siblings with DWS, and recorded coexistent conditions (by ICD10 category) were extracted for 187 patients (46.5% male, 43% from Asia) from 168 case reports. RESULTS: Diagnosis was most often set in 12 years old (27.8%). One-third of cases had a chromosomal abnormality or syndrome (n = 8 PHACE), 27% had a cardiovascular condition (n = 7 Patent Ductus Arteriosus), 24% had a disease of eye and ear (n = 9 cataract); most common malignancy was nephroblastoma (n = 8, all Asian). Almost one-fifth had a mental illness diagnosis; only 6.4% had mild or severe intellectual disability. CONCLUSION: The spread of comorbidities calls for early diagnosis and multidisciplinary research and practice, especially as many cases remain clinically asymptomatic for years

Geographical variation in dementia:Examining the role of environmental factors in Sweden and Scotland

BACKGROUND: This study aimed to estimate the magnitude of geographical variation in dementia rates and suggest explanations for this variation. Small-area studies are scarce, and none has adequately investigated the relative contribution of genetic and environmental factors to the distribution of dementia. METHODS: We present two complementary small-area hierarchical Bayesian disease mapping studies using the comprehensive Swedish Twin Registry (n=27,680) and the 1932 Scottish Mental Survey cohort (n=37,597). The twin study allowed us to isolate the area in order to examine the effect of unshared environmental factors. The Scottish Mental Survey study allowed us to examine various epochs in the life course – approximately age 11 years and adulthood. RESULTS: We found a 2-to 3- fold geographical variation in dementia odds in Sweden, after twin random effects – likely to capture genetic and shared environmental variance – were removed. In Scotland we found no variation in dementia odds in childhood but substantial variation, following a broadly similar pattern to Sweden, by adulthood. CONCLUSIONS: There is geographical variation in dementia rates. Most of this variation is likely to result from unshared environmental factors that have their effect in adolescence or later. Further work is required to confirm these findings and identify any potentially modifiable socio-environmental risk factors for dementia responsible for this geographical variation in risk. However, if these factors do exist and could be optimized in the whole population, our results suggest that dementia rates could be halved

Feistel Structures for MPC, and More

We study approaches to generalized Feistel constructions with low-degree round functions with a focus on x -> x^3 . Besides known constructions, we also provide a new balanced Feistel construction with improved diffusion properties. This then allows us to propose more efficient generalizations of the MiMC design (Asiacrypt’16), which we in turn evaluate in three application areas. Whereas MiMC was not competitive at all in a recently proposed new class of PQ-secure signature schemes, our new construction leads to about 30 times smaller signatures than MiMC. In MPC use cases, where MiMC outperforms all other competitors, we observe improvements in throughput by a factor of more than 4 and simultaneously a 5-fold reduction of preprocessing effort, albeit at the cost of a higher latency. Another use case where MiMC already outperforms other designs, in the area of SNARKs, sees modest improvements. Additionally, this use case benefits from the flexibility to use smaller fields

Anterior Medial Prefrontal Cortex Exhibits Activation during Task Preparation but Deactivation during Task Execution

BACKGROUND: The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. METHODOLOGY/PRINCIPAL FINDINGS: Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. CONCLUSIONS/SIGNIFICANCE: The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing