Risk-based cost-benefit analysis of alternative vaccines against COVID-19 in Brazil: Coronavac vs. Astrazeneca vs. Pfizer

We propose a probabilistic model to quantify the cost-benefit of mass Vaccination Scenarios (VSs) against COVID-19. Through this approach, we conduct a six-month simulation, from August 31st, 2021 to March 3rd, 2022, of nine VSs, i.e., the three primary vaccine brands in Brazil (CoronaVac, AstraZeneca and Pfizer), each with three different vaccination rates (2nd doses per week). Since each vaccine has different individual-level effectiveness, we measure the population-level benefit as the probability of reaching herd immunity (HI). We quantify and categorize the cost-benefit of VSs through risk graphs that show: (i) monetary cost vs. probability of reaching HI; and (ii) number of new deaths vs. probability of reaching HI. Results show that AstraZeneca has the best cost-benefit when prioritizing acquisition costs, while Pfizer is the most cost-beneficial when prioritizing the number of deaths. This work provides helpful information that can aid public health authorities in Brazil to better plan VSs. Furthermore, our approach is not restricted to Brazil, the COVID-19 pandemic, or the mentioned vaccine brands. Indeed, the method is flexible so that this study can be a valuable reference for future cost-benefit analyses in other countries and pandemics, especially in the early stages of vaccination, when data is scarce and uncertainty is high.     

Correcting forensic DNA errors

DNA mixture interpretation can produce opposing conclusions by qualified forensic analysts, even within the same laboratory. The long-delayed publication of the National Institutes of Standards and Technology (NIST) study of 109 North American crime laboratories in this journal demonstrates this most clearly. This latest study supports earlier work that shows common methods such as the Combined Probability of Inclusion (CPI) have wrongly included innocent people as contributors to DNA mixtures. The 2016 President's Council of Advisors on Science and Technology report concluded, “In summary, the interpretation of complex DNA mixtures with the CPI statistic has been an inadequately specified—and thus inappropriately subjective—method. As such, the method is clearly not foundationally valid” [7]. The adoption of probabilistic genotyping by many laboratories will certainly prevent some of these errors from occurring in the future, but the same laboratories that produced past errors can also now review old cases with their new software—without additional bench work. It is critical that laboratories adopt procedures and policies to do this.     

STRmix™ put to the test: 300 000 non-contributor profiles compared to four-contributor DNA mixtures and the impact of replicates

Probabilistic genotyping approaches are increasingly used for the interpretation of DNA mixtures. To explore the specificity of one of these systems (STRmix^™), we conducted an extensive study using 24 complex mixtures: all were known or apparent 4-person mixtures with at least one contributor representing less than 20% of total DNA, and all mixtures had at least one contributor with suboptimal DNA quantity. Those mixtures were either generated in-house or from casework. All the mixtures were compared to 300,000 virtual non-contributors, resulting in a dataset of 7.2 million comparisons. The great majority of the non-contributor comparisons led to a LR lower than 1 for a specificity of 99.1%. The effect of using replicate amplifications to calculate the LR of non-contributors was also assessed as triplicates were used and led to an increased specificity of 99.8%. The very large extent of the analyzed data shows that STRmix^™ has an excellent ability to discriminate non-contributors from complex DNA mixtures.     

带状灰质异位的磁共振弥散张量白质束成像研究

目的采用磁共振弥散张量白质束成像技术,观察带状灰质异位脑白质异常分布情况,探讨异位灰质的神经病理机制以及弥散张量白质束成像技术的应用价值。方法采用磁共振弥散张量白质束成像技术,对1例癫痫症状的带状灰质异位患者进行白质束描绘,观察其不同灰、白质的分布情况,并和1例正常人进行对比研究。结果弥散张量白质束成像技术很好地描绘了白质束结构。整体观察发现带状灰质异位患者脑白质整体结构紊乱,与正常人相比其联络弓状纤维稀疏、大部缺失,胼胝体纤维稀疏不整;局部分析发现内层灰质为主要的白质纤维发出处,而外层灰质仅发出细碎短小的纤维。结论对于带状灰质异位,异位的内层灰质不仅具有神经生理功能,并且可能起着主要作用,外层"正常"的灰质由于脑结构紊乱而丧失主要功能地位;灰质结构的紊乱导致白质纤维结构的缺失;弥散张量白质束成像技术可以很好地应用于带状灰质异位的神经机制研究。     

Multimodal, Multidimensional Models of Mouse Brain

Summary:  Naturally occurring mutants and genetically manipulated strains of mice are widely used to model a variety of human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison and to facilitate the integration of anatomic, genetic, and physiologic observations from multiple subjects and experiments. We have developed digital atlases of the C57BL/6J mouse brain (adult and neonate) as comprehensive frameworks for storing and accessing the myriad types of information about the mouse brain. Along with raw and annotated images, these contain database management systems and a set of tools for comparing information from different techniques and different animals. Each atlas establishes a canonical representation of the mouse brain and provides the tools for the manipulation and analysis of new data. We describe both these atlases and discuss how they may be put to use in organizing and analyzing data from mouse models of epilepsy.     

On a relaxation-labelling algorithm for quantitative assessment of tumour vasculature in tissue section images

Although tumour vasculature constitutes a biological factor playing a crucial role in the radiation response of tumours, the current procedures of assessment are semiquantitative, typically employing visual examination of stained histological material. Such techniques are also time consuming, and inefficient of extracting essential information on the vascular network. Image analysis has yet to contribute significantly in this direction, and most studies to date focus on blood vessel segmentation through empirical, user-selected thresholds. The present paper proposes an alternative segmentation approach, based on a probabilistic relaxation algorithm, applied in microscopic images of stained tissues. After image partitioning various information is obtained, such as vascular domains and geometrical characteristics of vessels.     

Multimodal architectonic mapping of human superior temporal gyrus

Although it is generally accepted that human superior temporal gyrus is activated by a huge variety of auditory and linguistic tasks, little is known about the exact positions and extents of cortical areas that are located on the lateral convexity of the gyrus (e.g., Brodmann’s area 22). Such information, however, is relevant for a rigorous testing of structural-functional relationships in both normal volunteers and patients suffering from disorders of auditory and language perception. The present combined cytoarchitectonic and receptorarchitectonic study identifies a distinct area (Te3) in the lateral bulge of the superior temporal gyrus by using an algorithm-based approach for the detection of cortical borders. Our mapping data show that, in contrast to Brodmann’s area (BA) 22, only small portions of Te3 reach the dorsal and ventral banks of the gyrus. Therefore, we labelled the newly defined area as “Te3” and not as “BA 22”. The cytoarchitectonically defined borders of Te3 coincide with abrupt changes in the receptorarchitecture of several classical neurotransmitters, suggesting that Te3 represents a functionally relevant area of the human superior temporal gyrus. Since position and extent of area Te3 varied considerably between subjects, probability maps were created that show for each voxel of the standard references space, the frequency with which Te3 was present in it. These maps, in combination with previously published maps of the primary auditory cortex, can directly be compared with functional imaging data, and may open new perspectives for the analysis of structural-functional correlations in the human auditory and language systems.     

Assessment of optic nerve and optic tract alterations in patients with orbital space-occupying lesions using probabilistic diffusion tractography

AIM: To investigate the diffusion changes in both the optic nerve and optic tract in orbital space-occupying lesion patients with decreased visual acuity, and its clinical significance using probabilistic diffusion tractography (PDT). METHODS: Twenty patients with orbital space-occupying lesions and 25 age- and gender-matched healthy persons were included. All patients and controls underwent routine orbital magnetic resonance imaging and diffusion tensor imaging (DTI), using a 3.0T magnetic resonance scanner (Trio Tim Siemens). After the image data were preprocessed, each DTI parameters of the optic nerve and optic tract was obtained by PDT, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). The asymmetry index (AI) of each parameter was calculated. Compared the parameters of the affected side optic nerve and ipsilateral optic tract with the contralateral side by paired sample t-test; compared AI of parameters of optic nerve and optic tract between the patient group and the control group by independent sample t-test. Patients were divided into three subgroups according to the low vision grade standard of WHO, compared the FA and AI of FA between the three subgroups by single factor variance analysis. RESULTS: The affected side optic nerve presented significantly decreased FA, increased MD, AD, and RD values compared to the unaffected side (P<0.05). The AI of FA, MD, AD, and RD of optic nerve in the patients was significantly higher than that of the controls (P<0.05). The comparison results of the optic tract showed that there was no significant difference between the patient group and control group in terms of the bilateral optic tracts in patients (P>0.05). The AIs of the FA value of the optic nerve in the eyesight <0.1 subgroup was significantly higher than that in the other groups (P<0.05). CONCLUSION: FA, MD, AD, and RD of the affected side optic nerve of the orbital space-occupying lesions have significantly changed, the FA value is the most sensitive. The PDT could be a useful tool to provide valid quantitative markers of optic nerve injuries and evaluate the severity of orbital diseases, which other examinations cannot be acquired.     

Deformation of the corona radiata and internal capsule in normal pressure hydrocephalus

Background and purposeThe pathophysiology of the clinical manifestations in normal pressure hydrocephalus (NPH) remains obscure. Ventricular dilatation could generate forces on the paracentral fibers of the corona radiata (CR), hence interfering with their function and producing the classical clinical triad. The analysis of the regional displacement and deformation of the white matter bundles, forming the corona radiata and internal capsule, may clarify the relationship between ventricular dilatation and clinical manifestations in NPH.MethodAn experimental finite element (FE) analysis was used to simulate ventricular dilatation in 3 dimensions (3D) and to calculate the strain and deformation on the surrounding parenchyma. Magnetic resonance diffusion tensor imaging-based white matter tractography was then applied to retrieve the displacement and deformation exerted along various fiber bundles of the corona radiata and internal capsule. Anterior and posterior limb displacements and elongations were compared using a paired samples t-test.ResultsThe internal capsule, hence the corona radiata, of each cerebral hemisphere was segmented into anterior and posterior limbs. Mean displacements and elongations were calculated for each limb. Mean displacement was significantly larger in the anterior limb whereas mean deformation was larger in the posterior limb (P < 0.01).ConclusionThe present simulation demonstrates that ventricular dilatation does not have a homogeneous effect on the periventricular fibre tracts, with a particular load on the corticospinal tract. The affection of this tract remains thereby a potential factor in the generation of the NPH gait disorders.