Some deterministic and stochastic mathematical models of naïve T-cell homeostasis

Humans live for decades, whereas mice live for months. Over these long timescales, naïve T cells die or divide infrequently enough that it makes sense to approximate death and division as instantaneous events. The population of T cells in the body is naturally divided into clonotypes; a clonotype is the set of cells that have identical T-cell receptors. While total numbers of cells, such as naïve CD4⁺ T cells, are large enough that ordinary differential equations are an appropriate starting point for mathematical models, the numbers of cells per clonotype are not. Here, we review a number of basic mathematical models of the maintenance of clonal diversity. As well as deterministic models, we discuss stochastic models that explicitly track the integer number of naïve T cells in many competing clonotypes over the lifetime of a mouse or human, including the effect of waning thymic production. Experimental evaluation of clonal diversity by bulk high-throughput sequencing has many difficulties, but the use of single-cell sequencing is restricted to numbers of cells many orders of magnitude smaller than the total number of T cells in the body. Mathematical questions associated with extrapolating from small samples are therefore key to advances in understanding the diversity of the repertoire of T cells. We conclude with some mathematical models on how to advance in this area.     

Power/sample size calculations for assessing correlates of risk in clinical efficacy trials

In a randomized controlled clinical trial that assesses treatment efficacy, a common objective is to assess the association of a measured biomarker response endpoint with the primary study endpoint in the active treatment group, using a case‐cohort, case‐control, or two‐phase sampling design. Methods for power and sample size calculations for such biomarker association analyses typically do not account for the level of treatment efficacy, precluding interpretation of the biomarker association results in terms of biomarker effect modification of treatment efficacy, with detriment that the power calculations may tacitly and inadvertently assume that the treatment harms some study participants. We develop power and sample size methods accounting for this issue, and the methods also account for inter‐individual variability of the biomarker that is not biologically relevant (e.g., due to technical measurement error). We focus on a binary study endpoint and on a biomarker subject to measurement error that is normally distributed or categorical with two or three levels. We illustrate the methods with preventive HIV vaccine efficacy trials and include an R package implementing the methods. Copyright © 2016 John Wiley & Sons, Ltd.     

Varying undersampling directions for accelerating multiple acquisition magnetic resonance imaging

In this study, we propose a new sampling strategy for efficiently accelerating multiple acquisition MRI. The new sampling strategy is to obtain data along different phase-encoding directions across multiple acquisitions. The proposed sampling strategy was evaluated in multicontrast MR imaging (T1, T2, proton density) and multiple phase-cycled (PC) balanced steady-state free precession (bSSFP) imaging by using convolutional neural networks with central and random sampling patterns. In vivo MRI acquisitions as well as a public database were used to test the concept. Based on both visual inspection and quantitative analysis, the proposed sampling strategy showed better performance than sampling along the same phase-encoding direction in both multicontrast MR imaging and multiple PC-bSSFP imaging, regardless of sampling pattern (central, random) or datasets (public, retrospective and prospective in vivo). For the prospective in vivo applications, acceleration was performed by sampling along different phase-encoding directions at the time of acquisition with a conventional rectangular field of view, which demonstrated the advantage of the proposed sampling strategy in the real environment. Preliminary trials on compressed sensing (CS) also demonstrated improvement of CS with the proposed idea. Sampling along different phase-encoding directions across multiple acquisitions is advantageous for accelerating multiacquisition MRI, irrespective of sampling pattern or datasets, with further improvement through transfer learning.     

Divergent estimates of HIV incidence among people who inject drugs in Ukraine

BackgroundDivergent estimates of HIV incidence among people who inject drugs (PWID) in Ukraine have been reported in modeling studies, longitudinal cohort studies, and recent infection assays used in cross-sectional surveys. Estimates range from 0.65 to 24.8 infections per 100 person-years with substantial regional variation. In this paper, we study the sources of this discrepancy.MethodsWe compared baseline characteristics of study subjects recruited in the cross-sectional integrated bio-behavioral surveillance surveys (IBBS) in 2011 and 2013, with those from the longitudinal network intervention trial (network RCT) conducted between 2010 – 2013, the study that found a remarkably high incidence of HIV among PWID in Ukraine. The analysis was conducted for two cities: Mykolaiv and Odesa.ResultsSignificant differences were found in the characteristics of study subjects recruited in the IBBS surveys and the network RCT, in particular in Odesa, where the mismatch in the estimates of HIV incidence is greatest. In Odesa, recent syringe sharing was about three times as prevalent in the network RCT as in the IBBS; 39% of the network RCT and 16–18% of the IBBS participants indicated stimulants rather than opiates as their drug of choice; 97% of respondents in the network RCT and 45% in the IBBS-2013 reported injecting in a group over half of the time; and the average monthly number of injections in the network RCT was about twice that in the IBBS studies.ConclusionsDifferences in study designs and sampling methodologies may be responsible for the substantial differences in HIV incidence estimates among PWID in Ukraine. The potential sources of selection bias differed between the studies and likely resulted in the recruitment of lower risk individuals into the IBBS studies compared to the network RCT. Risk stratification in the population of PWID may have implications for future surveillance and intervention efforts.     

药品抽检在健康中国建设中发挥的作用探讨

目的 通过探讨中国药品抽检对健康中国的作用，为加强药品抽检促进健康中国建设提供参考。方法 分析健康中国建设对药品质量的要求以及药品抽检对药品质量提升和健康中国建设的作用，为药品抽检更好助力健康中国建设提出建议。结果 健康中国建设需要优质的药品，然而药品质量风险具有客观性，药品监管需常抓不懈。中国药品抽检覆盖药品生产、经营和使用环节以及高风险品种，以问题为导向防控药品质量风险并严惩不法行为，使中国药品总体质量处于较高水平，并且可以通过减少假劣药品、提升药品质量和警示用药风险为健康中国建设贡献力量。结论 中国药品抽检对健康中国建设具有重要意义，下一步工作中应践行“四个最严”要求、提高抽检品种遴选的靶向性、联合惩戒制售假劣药品行为、加大查处力度，更好地为健康中国建设把好药品质量关。     

Anatomical Variations of the Left Adrenal Vein Encountered During Venous Sampling

PurposeTo identify anatomical variations in the left adrenal vein (LAV) and to evaluate the role of preprocedural contrast-enhanced computed tomography (CT) planning.MethodsThe length of the left adrenal central vein (LACV), the vessel that receives blood from all tributaries of the left adrenal gland, was measured using venograms of patients who had undergone adrenal venous sampling (AVS) for the diagnosis of primary aldosteronism between October 2017 and December 2019. The anatomical variants of the LAV were described and classified. Contrast-enhanced CT was used to evaluate the detection rate of the following: (a) confluence of the left inferior phrenic vein and the LAV and (b) the last tributary flowing into the LAV.ResultsIn total, 311 patients (143 men, 168 women; mean age: 49.3 years ± 11.0) were enrolled. Of them, 9 (2.9%) patients had anatomical variants lacking a LACV. In patients with a LACV (n = 302), the venographic LACV length was 9.0 mm ± 3.9 (<1 mm in 9 patients). The detection rate of the confluence of the left inferior phrenic vein and LAV, as determined using contrast-enhanced CT, was high (96.2%), whereas that of the last tributary flowing into the LAV was low (0.8%). In 4 of 18 patients with short or absent LACV, the variant was visualized using contrast-enhanced CT.ConclusionsIn some patients, the LACV is absent or short, which is an anatomical variation. Understanding venographic anatomical variations can help avoid misleading results resulting from a suboptimal sampling site in AVS. For some subtypes, contrast-enhanced CT may also help in planning the AVS procedure.     

采血换纸装置的研制与在静脉穿刺中的应用

目的:研发一种采血换纸装置,用于静脉穿刺时的纸巾更换,以预防患者在医院内的交叉感染。方法:采血换纸装置由支撑台、送纸筒、收纸筒、驱动收纸滚筒的旋转电机驱动机构以及输送机构组成,将采血换纸装置平放在静脉抽血操作台上进行操作,采血前后一人一巾更换。选取体检抽血的30名体检者,按随机数表法将其分为对照组和观察组,每组15名。采血时对照组采用传统更换纸巾方法,观察组采用采血换纸装置,对比分析两组医护人员更换采血纸巾的时间。结果:在6次采血试验中,观察组和对照组1人次平均完成采血时间分别为(61.67±7.26)s和(75.67±9.31)s,两组1人次、5人次、10人次和15人次的平均完成时间比较,差异均有统计学意义(t=0.270,t=0.117,t=0.773,t=0.798;P<0.05),且缩短了采血等候时间。结论:采血换纸装置优化了医护人员更换采血纸巾的方法,可节约采血时间,提高医护人员工作效率,有效预防院内交叉感染的风险。     

Multilattice sampling strategies for region of interest dynamic MRI

A multilattice sampling approach is proposed for dynamic MRI with Cartesian trajectories. It relies on the use of sampling patterns composed of several different lattices and exploits an image model where only some parts of the image are dynamic, whereas the rest is assumed static. Given the parameters of such an image model, the methodology followed for the design of a multilattice sampling pattern adapted to the model is described. The multi‐lattice approach is compared to single‐lattice sampling, as used by traditional acceleration methods such as UNFOLD (UNaliasing by Fourier‐Encoding the Overlaps using the temporal Dimension) or k‐t BLAST, and random sampling used by modern compressed sensing‐based methods. On the considered image model, it allows more flexibility and higher accelerations than lattice sampling and better performance than random sampling. The method is illustrated on a phase‐contrast carotid blood velocity mapping MR experiment. Combining the multilattice approach with the KEYHOLE technique allows up to 12× acceleration factors. Simulation and in vivo undersampling results validate the method. Compared to lattice and random sampling, multilattice sampling provides significant gains at high acceleration factors. Magn Reson Med 70:392–403, 2013. © 2012 Wiley Periodicals, Inc.     

Quality of experience during horticultural activities: an experience sampling pilot study among older adults living in a nursing home

Horticulture was shown to represent a well-being source for older adults, encompassing the physical, mental and social domains. Aim of this pilot study was to contribute to extant literature through the investigation of the quality of experience associated with horticultural versus occupational activities. A group of 11 older residents of a nursing home were involved in a crossover study with a baseline measure. Participants attended weekly horticultural and occupational sessions for two six-week cycles. Experience Sampling Method was administered before the program and after each session, to assess participants' levels of happiness, concentration, sociability, involvement, challenges and stakes, and self-satisfaction. Altogether, 332 self-report questionnaires were collected.Findings showed that participants' levels of the cognitive and motivational variables increased during both activities, but horticulture was also perceived as providing higher challenges and stakes, and improving self-satisfaction. Results can have practical implications for well-being promotion among older adults through meaningful activity engagement.