HIV and respiratory illness in the antiretroviral therapy era

Respiratory illness is a common manifestation of HIV infection. The availability of effective antiretroviral therapy (ART) has changed the pattern of respiratory ill-health experienced by people living with HIV (PLWH). Among populations with good access to ART, opportunistic respiratory infections such as Pneumocystis jirovecii pneumonia (PCP) are becoming less frequent. However, there is evidence to suggest that these populations may be at greater risk of serious non-AIDS illness including chronic respiratory disease. Although there is remaining uncertainty about the extent to which HIV represents an independent risk-factor for respiratory illness in individuals with a suppressed HIV viral load and immune reconstitution, in many settings PLWH have greater exposure to risk factors for respiratory illness (in particular tobacco smoking), which contribute to this burden of disease. As HIV-positive populations age, management of these conditions will therefore become increasingly important. Healthcare services need to manage this growing burden of chronic respiratory illness and provide access to preventative measures including smoking cessation and immunisation against vaccine-preventable respiratory infections in a way that is appropriate to the populations served

Role of necroptosis in the pathogenesis of solid organ injury

Necroptosis is a type of regulated cell death dependent on the activity of receptor-interacting serine/threonine-protein (RIP) kinases. However, unlike apoptosis, it is caspase independent. Increasing evidence has implicated necroptosis in the pathogenesis of disease, including ischemic injury, neurodegeneration, viral infection and many others. Key players of the necroptosis signalling pathway are now widely recognized as therapeutic targets. Necrostatins may be developed as potent inhibitors of necroptosis, targeting the activity of RIPK1. Necrostatin-1, the first generation of necrostatins, has been shown to confer potent protective effects in different animal models. This review will summarize novel insights into the involvement of necroptosis in specific injury of different organs, and the therapeutic platform that it provides for treatment

Mixed Convection From an Isothermal Rough Plate

While there are studies of mixed convection heat transfer from a smooth plate, studies of this phenomenon from an external rough plate are absent. The derivation by Jaffer (2023) of the heat transfer formula for natural convection from an external plate implies a simple relation between heat transfer and fluid velocity. This relation leads to formulas for mixed convection from horizontal and vertical rough plates; these formulas are then combined to predict the mixed convection heat transfer at any plate inclination. Heat transfer measurements of a 30.5 cm square rough plate with forced air velocities between 0.1 m/s and 2.5 m/s were made in each orthogonal combination of plate and airflow direction, and of a tilted downward-facing plate. Each data-set matches the present theory with root-mean-squared relative error between 1.4% and 4%.Comment: 33 pages; 39 figures; 12 tables; 19 reference

Natural scene statistics and the structure of orientation maps in the visual cortex

Visual activity after eye-opening influences feature map structure in primary visual cortex (V1). For instance, rearing cats in an environment of stripes of one orientation yields an over-representation of that orientation in V1. However, whether such changes also affect the higher-order statistics of orientation maps is unknown. A statistical bias of orientation maps in normally raised animals is that the probability of the angular difference in orientation preference between each pair of points in the cortex depends on the angle of the line joining those points relative to a fixed but arbitrary set of axes. Natural images show an analogous statistical bias; however, whether this drives the development of comparable structure in V1 is unknown. We examined these statistics for normal, stripe-reared and dark-reared cats, and found that the biases present were not consistently related to those present in the input, or to genetic relationships. We compared these results with two computational models of orientation map development, an analytical model and a Hebbian model. The analytical model failed to reproduce the experimentally observed statistics. In the Hebbian model, while orientation difference statistics could be strongly driven by the input, statistics similar to those seen in experimental maps arose only when symmetry breaking was allowed to occur spontaneously. These results suggest that these statistical biases of orientation maps arise primarily spontaneously, rather than being governed by either input statistics or genetic mechanisms

Self Consistent Molecular Field Theory for Packing in Classical Liquids

Building on a quasi-chemical formulation of solution theory, this paper proposes a self consistent molecular field theory for packing problems in classical liquids, and tests the theoretical predictions for the excess chemical potential of the hard sphere fluid. Results are given for the self consistent molecular fields obtained, and for the probabilities of occupancy of a molecular observation volume. For this system, the excess chemical potential predicted is as accurate as the most accurate prior theories, particularly the scaled particle (Percus-Yevick compressibility) theory. It is argued that the present approach is particularly simple, and should provide a basis for a molecular-scale description of more complex solutions.Comment: 6 pages and 5 figure

A spectro-polarimetric study of the planet-hosting G dwarf, HD 147513

The results from a spectro-polarimetric study of the planet-hosting Sun-like star, HD 147513 (G5V), are presented here. Robust detections of Zeeman signatures at all observed epochs indicate a surface magnetic field, with longitudinal magnetic field strengths varying between 1.0–3.2 G. Radial velocity variations from night to night modulate on a similar timescale to the longitudinal magnetic field measurements. These variations are therefore likely due to the rotational modulation of stellar active regions rather than the much longer timescale of the planetary orbit (Porb = 528 d). Both the longitudinal magnetic field measurements and radial velocity variations are consistent with a rotation period of 10 ± 2 days, which are also consistent with the measured chromospheric activity level of the star (′log R′HK = -4.64). Together, these quantities indicate a low inclination angle, i ~ 18°. We present preliminary magnetic field maps of the star based on the above period and find a simple poloidal large-scale field. Chemical analyses of the star have revealed that it is likely to have undergone a barium-enrichment phase in its evolution because of a higher mass companion. Despite this, our study reveals that the star has a fairly typical activity level for its rotation period and spectral type. Future studies will enable us to explore the long-term evolution of the field, as well as to measure the stellar rotation period, with greater accuracy.Publisher PDFPeer reviewe

International standards for fetal brain structures based on serial ultrasound measurements from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

OBJECTIVE: To create prescriptive growth standards for five fetal brain structures, measured by ultrasound, from healthy, well-nourished women, at low risk of impaired fetal growth and poor perinatal outcomes, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project. METHODS: This was a complementary analysis of a large, population-based, multicentre, longitudinal study. We measured, in planes reconstructed from 3-dimensional (3D) ultrasound volumes of the fetal head at different time points in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle (AV), atrium of the posterior ventricle (PV) and cisterna magna (CM). The sample analysed was randomly selected from the overall FGLS population, ensuring an equal distribution amongst the eight diverse participating sites and of 3D ultrasound volumes across pregnancy (range: 15 - 36 weeks' gestation). Fractional polynomials were used to the construct standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards. RESULTS: From the entire FGLS cohort of 4321 women, 451 (10.4%) were randomly selected. After exclusions, 3D ultrasound volumes from 442 fetuses born without congenital malformations were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures showed increasing size with gestation and increasing variability for the POF, SF, PV and CM. The 3rd , 5th , 50th , 95th and 97th smoothed centile are presented. The 5th centile of POF and SF were 2.8 and 4.3 at 22 weeks and 4.2 and 9.4mm at 32 weeks respectively. The 95th centile of PV and CM were 8.5 and 7.4 at 22 weeks and 8.5 and 9.4mm at 32 weeks respectively. CONCLUSIONS: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcomes. We recommend these as international standards for the assessment of measurements obtained by ultrasound from fetal brain structures

Design of SkSP-R Plan for Popular Statistical Distributions

The design of a Skip-lot sampling plan of type SkSP-R is presented for time truncated life test for the Weibull, Exponentiated Weibull, and Birnbaum-Saunders lifetime distributions. The plan parameters of the SkSP-R plan under these three distributions are determined through a nonlinear optimization problem. Tables are also constructed for each distribution. The advantages of the proposed plan over the existing sampling schemes are discussed. Application of the proposed plan is explained with the help of an example. The Birnbaum-Saunders distribution is economically superior to other two distributions in terms of minimum average sample number

The objectives, design and implementation of the INTERGROWTH-21st Project

INTERGROWTH-21st is a multicentre, multiethnic, populationbased project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship between birthweight, length and head circumference, gestational age and perinatal outcomes. As the project has selected healthy cohorts with no obvious risk factors for intrauterine growth restriction, these standards will describe how all fetuses and newborns should grow, as opposed to traditional charts that describe how some have grown at a given place and time. These growth patterns will be related to morbidity and mortality to identify levels of perinatal risk. Additional aims include phenotypic characterisation of the preterm and impaired fetal growth syndromes and development of a prediction model, based on multiple ultrasound measurements, to estimate gestational age for use in pregnant women without access to early/frequent antenatal care

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts