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Following the emergence of COVID-19 at the end of 2019, several mathematical models have been developed to study the transmission dynamics of this disease. Many of these models assume homogeneous mixing in the underlying population. However, contact rates and mixing patterns can vary dramatically among individuals depending on their age and activity level. Variation in contact rates among age groups and over time can significantly impact how well a model captures observed trends. To properly model the age-dependent dynamics of COVID-19 and understand the impacts of interventions, it is essential to consider heterogeneity arising from contact rates and mixing patterns. We developed an age-structured model that incorporates time-varying contact rates and population mixing computed from the ongoing BC Mix COVID-19 survey to study transmission dynamics of COVID-19 in British Columbia (BC), Canada. Using a Bayesian inference framework, we fit four versions of our model to weekly reported cases of COVID-19 in BC, with each version allowing different assumptions of contact rates. We show that in addition to incorporating age-specific contact rates and mixing patterns, time-dependent (weekly) contact rates are needed to adequately capture the observed transmission dynamics of COVID-19. see more Our approach provides a framework for explicitly including empirical contact rates in a transmission model, which removes the need to otherwise model the impact of many non-pharmaceutical interventions. Further, this approach allows projection of future cases based on clear assumptions of age-specific contact rates, as opposed to less tractable assumptions regarding transmission rates.Neutralizing antibodies are one available tool for the treatment of infectious diseases. Speed in developing monoclonal antibody treatments is an understood requirement for emerging infectious diseases, and need for COVID-19 treatments during the worldwide pandemic has provided additional urgency. Process development (at Regeneron) and technology transfer (within Regeneron and to Genentech) of casirivimab and imdevimab (REGEN-COV™ or Ronapreve™) manufacturing processes have addressed speed and need with selected purification and cell culture examples provided, respectively, for these two development challenges. This was achieved through three key pillars (1) Regeneron's proprietary Velocisuite® technologies, (2) deep monoclonal antibody process and manufacturing knowledge at both companies, and (3) Regeneron's and Genentech's commitment to deliver therapeutics to patients in need. Combined with business processes and risk management, these pillars rapidly allowed casirivimab and imdevimab to move to clinical manufacturing and to production at Genentech in a first-time process transfer under compressed timelines between the companies.We aimed to review the available reports of psychiatric adverse reactions to COVID vaccines. Electronic databases such as PubMed and Google scholar were combed to identify relevant reports. We found a total of 11 reports describing 14 cases of psychiatric reactions; these were mostly altered mental states, psychosis, mania, depression, and functional neurological disorder. The index case was commonly a young or middle-aged adult. All reports pertained to the use of either mRNA or vector-based vaccines. Symptom onset was within 10 days of vaccination in all cases; as such, this seems to be a high-risk period warranting vigilance.
To assess the feasibility, patient tolerance, pharmacokinetics, and potential effectiveness of a randomized controlled trial protocol investigating intravenous calcium chloride for the prevention of uterine atony during cesarean delivery.

Double-blind, randomized controlled pilot trial with nested population pharmacokinetic analysis.

This study was performed at Lucile Packard Children's Hospital, from August 2018 to September 2019.

Forty patients with at least two risk factors for uterine atony at the time of cesarean delivery.

One gram of intravenous calcium chloride (n=20 patients) or a saline placebo control (n=20 patients), in addition to standard care with oxytocin, upon umbilical cord clamping.

The primary efficacy-related outcome was the presence of uterine atony defined as the use of a second-line uterotonic medication, surgical interventions for atony, or hemorrhage with blood loss >1000 mL. Blood loss, uterine tone numerical rating scores, serial venous blood calcium levels, hemodynam or concern for adverse side effects. These encouraging findings warrant further investigation of calcium as a novel agent to prevent uterine atony with an adequately powered clinical trial. Clinical trial registry NCT03867383 https//clinicaltrials.gov/ct2/show/NCT03867383.
In this pilot study, investigators found that intravenous calcium chloride was well-tolerated by the 20 patients assigned to receive the study drug and may be effective in prevention of uterine atony. A 1-g dose was sufficient to substantially increase calcium levels without any critically elevated lab values or concern for adverse side effects. These encouraging findings warrant further investigation of calcium as a novel agent to prevent uterine atony with an adequately powered clinical trial. Clinical trial registry NCT03867383 https//clinicaltrials.gov/ct2/show/NCT03867383.
The unprecedented challenges introduced by the Coronavirus disease 2019 (COVID-19) pandemic may be amplified for children with autism spectrum disorder (ASD) and their families.

The current study aimed to describe the experiences of children with ASD and their families during the pandemic and to identify the needs of this community during emergency situations.

Participants were 122 parents of 122 children and adolescents (aged 3-18 years; one parent per family participated) with ASD living in Arizona, USA who participated in the first time point (July/August 2020) of a larger longitudinal survey study. A qualitative approach based in grounded theory methodology was used to analyze six open-ended survey questions.

The resulting conceptual model included a core category, Longing for Stability, and four main categories Public Health Measures Yielding New Challenges and Unexpected Gains, Experiencing Abrupt Changes across Developmental Domains, Changing Family Dynamics, and Protective Factors.

Findings add to limited research examining whether, and how, emergency events uniquely impact the ASD community, identifying potential methods by which services can be proactively adapted to best support the needs of children with ASD.
Findings add to limited research examining whether, and how, emergency events uniquely impact the ASD community, identifying potential methods by which services can be proactively adapted to best support the needs of children with ASD.
To establish a prognostic stratification model for predicting prognosis in patients with pancreatic ductal adenocarcinoma (PDAC) after curative resection based on preoperative contrast-enhanced computed tomography (CECT) findings.

From January 2014 to June 2020, 126 patients with radically resected PDAC were reviewed and divided into a development cohort (n=90) and a validation cohort (n=36). In the development cohort, clinicopathological parameters and preoperative CECT findings associated with recurrence-free survival (RFS) and overall survival (OS) were identified by using univariate and multivariate analyses. Nomograms were constructed based on Cox proportional hazards regression models. New prognostic nomograms were certificated in the validation cohort. Model performance was evaluated based on calibration, discrimination, and clinical utility.

Tumor size >4cm, adjacent organs invasion, suspicious lymph nodes, and rim enhancement were independently associated with worse RFS and OS (all P values were<0.05). In the validation cohort, the nomograms based on pancreatic CECT showed good discrimination capability and outperformed the TNM staging system in outcomes prediction. Patients were stratified into low- and high-risk groups based on nomograms, and RFS and OS rates in the low-risk group were significantly higher than those in the high-risk group (P<0.001 and <0.01, respectively).

Nomograms based on preoperative pancreatic CECT findings can predict RFS and OS for PDAC patients after curative resection and facilitate further prognostic stratification.
Nomograms based on preoperative pancreatic CECT findings can predict RFS and OS for PDAC patients after curative resection and facilitate further prognostic stratification.
This study evaluated the frequency and the effects of S. mutans and S. sobrinus on Decayed, Missing, and Filled Teeth (DMFT) scores in Iranian and Afghan populations. Serotyping of S. mutans isolates and multi-locus sequence typing (MLST) were the secondary goals.

This study was performed on 360 saliva and plaque samples from people from age groups of 4-7 and 15-17 years with Iranian and Afghan nationality who were residents of Tehran province. The DMFT index of the study population was determined, and S. mutans and S. sobrinus were identified using species-specific primers. Following the collagen-binding protein of S. mutans (cnm) gene identification, serotypes were determined, and genotyping was performed on eight selected isolates by assessing eight loci in the existing MLST scheme.

Of 360 samples, 300 were recruited as population study. Of these, 204 (51%) harbored S. mutans alone. In 42 specimens (10.5%), both specious were detected, and 54 (13.5%) were free of both. The frequencies of c, f, e, andtudy should be considered as emerging strains.Specific amino acid substitutions in degenerin mechano-gated channels (DEGs) of C. elegans convert these channels into constitutively active mutants that induce the degeneration of neurons where DEGs are expressed. Acid-sensing ion channel-2a (ASIC2a), a proton-gated cation channel predominantly expressed in central neurons, is a mammalian ortholog of DEGs, and it can remain unclosed to be cytotoxic once the same mutations as the DEG mutants are introduced into its gene. Here we show that heterozygous transgenic (Tg) rats expressing ASIC2a-G430F (ASIC2aG430F), the most active form of the gain-of-function mutants, under the control of the intrinsic ASIC2a promoter exhibited marked cerebellar maldevelopment with mild whole-brain atrophy. The Tg rats were small and developed an early-onset ataxic gait, as evidenced by rotarod and footprint tests. The overall gross-anatomy of the Tg brain was normal just after birth, but a reduction in brain volume, especially cerebellar volume, gradually emerged with age. Histological examination of the adult Tg brain revealed that the cell-densities of cerebellar Purkinje and granule cells were markedly reduced, while the cytoarchitecture of other brain regions was not significantly altered. RT-PCR and immunoblot analyses demonstrated that ASIC2aG430F transcripts and proteins were already present in various regions of the neonatal Tg brain before the deforming cerebellum became apparent. These results suggest that, according to the spatiotemporal pattern of the wild-type (WT) ASIC2a gene expression, the ASIC2aG430F channel induced lethal degeneration in Tg brain neurons expressing both ASIC2aG430F and ASIC2a channels.
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