NuvoteQ
Developer
Despite effective screening modalities, cervical cancer remains a leading cause of cancer-related death among women in the United States aged 20 to 39 years old, and incidence is rising in women aged 30-44 years old. Up to 25% of patients who are screened for cervical cancer by testing for human papillomavirus (HPV) do not receive necessary follow-up care with current laboratory-based testing. Applying a user-centered design approach, we surveyed and interviewed practicing clinicians to establish the use case, value proposition, and user requirements of a cervical cancer screening test for use in Indiana, USA. Insights from these stakeholders directly informed design specifications for a point-of-care HPV test capable of providing same-visit results to improve patient follow-up and retention. Guided by these requirements, we designed an isothermal nucleic acid amplification platform suitable for outpatient clinics. The test accepts swabbed endocervical cells, amplifies HPV16 L1 DNA
via
recombinase polymerase amplification, and provides results within 40 minutes on a lateral flow assay. Further, the test achieves a clinically relevant limit of detection of 1000 HPV 16 copies per reaction and verifies swabbing technique and test operation with a sample adequacy control. The test operation was designed for a minimally-trained user and decreases time-sensitive steps that would interfere with clinical flow. By integrating clinician input to inform development decisions, our device is uniquely tailored to meet the context-specific needs of primary care clinics. This work exemplifies how user-centered design can yield novel diagnostic technologies with greater clinical impact and adoption potential.
We propose a new method to address the nonparametric Behrens-Fisher problem, allowing for unequal distribution functions across the two samples. The procedure tests the null hypothesis H0:θ=1/2$\mathcal {H}_0: \theta = \nicefrac {1}{2}$ , where θ=P(X
In order to further understand the dilatancy phenomenon of rock, the conventional triaxial compression test and unloading confining pressure test are carried out with coarse sandstone, and the rock sample underwent single slope shear failure, and the deviatoric stress-strain curve of rock sample without confining pressure is obtained. Combined with the deviatoric stress-axial strain curve, the rock dilatancy process is divided into linear elastic stage, slow relative dilatancy stage, accelerated relative dilatancy stage and absolute dilatancy stage. The concepts of narrow dilatancy (absolute dilatancy) and generalized dilatancy (relative dilatancy) are proposed, and the fracture evolution law of different dilatancy stages is analyzed by numerical simulation. According to the bilinear dilatancy model, the general rules of apparent dilatancy angle and dilatancy index are analyzed. The results show that the apparent dilatancy angle in the conventional triaxial compression test decreases from 66.12° to 39.15°, with a decrease rate of 40.79%;the apparent dilatancy angle decreased from 63.44° to 48.22° in the unloading confining pressure test, with a decrease rate of 23.99%; and the confining pressure of 15 MPa is the demarcation point of the dilatancy index.In both tests, the characteristic stress thresholds (crack initiation stress σ
ci
, damage stress σ
cd
, peak strength σ
p
) increased with the increase of confining pressure. The dilatancy strain at different dilatancy stages decreases as the confining pressure increases, and the volume strain after unloading confining pressure is greater than that after the conventional triaxial loading. The phenomenon of rock dilatancy mainly occurs in the accelerated relative dilatancy stage and the absolute dilatancy stage, and the proportion of volume strain in the two stages is 76.73%. The research results provide an effective method for analyzing the phenomenon of rock dilatancy.
The displaced object recognition test (DORT), open field test (OFT), and three-chamber social approach test are standard behavioral assays used to assess the various aspects of cognition, emotional regulation, and social behavior in rodent models. This protocol introduces the use of these three tests to comprehensively evaluate the therapeutic effects of antisense oligonucleotide (ASO)-mediated exon-skipping therapies in neuromuscular disease models, such as Duchenne muscular dystrophy (DMD). Exon-skipping therapies aim to restore dystrophin expression, which can potentially influence cognitive, emotional, and social functions. By combining these tests, a multifaceted assessment of therapeutic efficacy can be achieved. This protocol is applicable not only to exon 51/53-skipping therapies but also to other exon-skipping treatments, enabling a broad evaluation of the therapeutic impact on cognition, emotional regulation, and social behavior.
According to observational studies, dietary habits may influence the occurrence of multiple sclerosis (MS). There are, however, only a few Mendelian randomization (MR) studies on both.
The objective of this two-sample MR study was to examine possible causal associations between the twenty-one dietary practices and MS. For this investigation, we employed MR analysis utilizing generally accessible statistics from genome-wide association studies (GWAS) to examine causal connections between dietary habits and MS susceptibility among persons of European descent. The IEU Open GWAS project (https://gwas.mrcieu.ac.uk/) provided these GWAS data. Pleiotropy and heterogeneity were investigated using the MR-Egger Intercept test and Cochran's Q test, respectively. MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode were used to assess the causal relationship between 21 dietary habit levels and MS.
After removing outliers, we found a significant association between genetically induced oily fish intake and MS risk (IVW, OR: 0.557; 95% CI: 0.351-0.884; p = 0.013). Extensive sensitivity analyses confirmed this result. Other dietary habits had no dis-cernible relationship with MS risk.
This MR analysis provides evidence of an association be-tween dietary patterns and the risk of developing MS. Notably, higher intake of oily fish was associated with a reduced risk of MS among individuals of European ancestry.
EDCTP2
Career Development Fellowship (CDF)
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