Differences in the haematological profile of healthy 70 year old men and women: normal ranges with confirmatory factor analysis

<p>Abstract</p> <p>Background</p> <p>Reference ranges are available for different blood cell counts. These ranges treat each cell type independently and do not consider possible correlations between cell types.</p> <p>Methods</p> <p>Participants were identified from the Community Health Index as survivors of the 1947 Scottish Mental Survey, all born in 1936, who were resident in Lothian (potential n = 3,810) and invited to participate in the study. Those who consented were invited to attend a Clinical Research Facility where, amongst other assessments, blood was taken for full blood count. First we described cell count data and bivariate correlations. Next we performed principal components analysis to identify common factors. Finally we performed confirmatory factor analysis to evaluate suitable models explaining relationships between cell counts in men and women.</p> <p>Results</p> <p>We examined blood cell counts in 1027 community-resident people with mean age 69.5 (range 67.6-71.3) years. We determined normal ranges for each cell type using Q-Q plots which showed that these ranges were significantly different between men and women for all cell types except basophils. We identified three principal components explaining around 60% of total variance of cell counts. Varimax rotation indicated that these could be considered as erythropoietic, leukopoietic and thrombopoietic factors. We showed that these factors were distinct for men and women by confirmatory factor analysis: in men neutrophil count was part of a 'thrombopoietic' trait whereas for women it was part of a 'leukopoietic' trait.</p> <p>Conclusions</p> <p>First, normal ranges for haematological indices should be sex-specific; at present this only pertains to those associated with erythrocytes. Second, differences between individuals across a range of blood cell counts can be explained to a considerable extent by three major components, but these components are not the same in men and women.</p

A Cooperative Interaction between Nontranslated RNA Sequences and NS5A Protein Promotes In Vivo Fitness of a Chimeric Hepatitis C/GB Virus B

GB virus B (GBV-B) is closely related to hepatitis C virus (HCV), infects small non-human primates, and is thus a valuable surrogate for studying HCV. Despite significant differences, the 5′ nontranslated RNAs (NTRs) of these viruses fold into four similar structured domains (I-IV), with domains II-III-IV comprising the viral internal ribosomal entry site (IRES). We previously reported the in vivo rescue of a chimeric GBV-B (vGB/IIIHC) containing HCV sequence in domain III, an essential segment of the IRES. We show here that three mutations identified within the vGB/IIIHC genome (within the 3′NTR, upstream of the poly(U) tract, and NS5A coding sequence) are necessary and sufficient for production of this chimeric virus following intrahepatic inoculation of synthetic RNA in tamarins, and thus apparently compensate for the presence of HCV sequence in domain III. To assess the mechanism(s) underlying these compensatory mutations, and to determine whether 5′NTR subdomains participating in genome replication do so in a virus-specific fashion, we constructed and evaluated a series of chimeric subgenomic GBV-B replicons in which various 5′NTR subdomains were substituted with their HCV homologs. Domains I and II of the GBV-B 5′NTR could not be replaced with HCV sequence, indicating that they contain essential, virus-specific RNA replication elements. In contrast, domain III could be swapped with minimal loss of genome replication capacity in cell culture. The 3′NTR and NS5A mutations required for rescue of the related chimeric virus in vivo had no effect on replication of the subgenomic GBneoD/IIIHC RNA in vitro. The data suggest that in vivo fitness of the domain III chimeric virus is dependent on a cooperative interaction between the 5′NTR, 3′NTR and NS5A at a step in the viral life cycle subsequent to genome replication, most likely during particle assembly. Such a mechanism may be common to all hepaciviruses

The large trans-Neptunian object 2002 TC302 from combined stellar occultation, photometry, and astrometry data

Context. Deriving physical properties of trans-Neptunian objects is important for the understanding of our Solar System. This requires observational efforts and the development of techniques suitable for these studies. Aims. Our aim is to characterize the large trans-Neptunian object (TNO) 2002 TC302. Methods. Stellar occultations offer unique opportunities to determine key physical properties of TNOs. On 28 January 2018, 2002 TC302 occulted a mv ~ 15.3 star with designation 593-005847 in the UCAC4 stellar catalog, corresponding to Gaia source 130957813463146112. Twelve positive occultation chords were obtained from Italy, France, Slovenia, and Switzerland. Also, four negative detections were obtained near the north and south limbs. This represents the best observed stellar occultation by a TNO other than Pluto in terms of the number of chords published thus far. From the 12 chords, an accurate elliptical fit to the instantaneous projection of the body can be obtained that is compatible with the near misses. Results. The resulting ellipse has major and minor axes of 543 ± 18 km and 460 ± 11 km, respectively, with a position angle of 3 ± 1 degrees for the minor axis. This information, combined with rotational light curves obtained with the 1.5 m telescope at Sierra Nevada Observatory and the 1.23 m telescope at Calar Alto observatory, allows us to derive possible three-dimensional shapes and density estimations for the body based on hydrostatic equilibrium assumptions. The effective diameter in equivalent area is around 84 km smaller than the radiometrically derived diameter using thermal data from Herschel and Spitzer Space Telescopes. This might indicate the existence of an unresolved satellite of up to ~300 km in diameter, which is required to account for all the thermal flux, although the occultation and thermal diameters are compatible within their error bars given the considerable uncertainty of the thermal results. The existence of a potential satellite also appears to be consistent with other ground-based data presented here. From the effective occultation diameter combined with absolute magnitude measurements we derive a geometric albedo of 0.147 ± 0.005, which would be somewhat smaller if 2002 TC302 has a satellite. The best occultation light curves do not show any signs of ring features or any signatures of a global atmosphere.Funding from Spanish projects AYA2014-56637-C2-1-P, AYA2017-89637-R, from FEDER, and Proyecto de Excelencia de la Junta de Andalucía 2012-FQM1776 is acknowledged. We would like to acknowledge financial support by the Spanish grant AYA-RTI2018-098657-JI00 “LEO-SBNAF” (MCIU/AEI/FEDER, UE) and the financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía (SEV- 2017-0709). Part of the research received funding from the European Union’s Horizon 2020 Research and Innovation Programme, under grant agreement no. 687378 and from the ERC programme under Grant Agreement no. 669416 Lucky Star. The following authors acknowledge the respective CNPq grants: FB-R 309578/2017-5; RV-M 304544/2017-5, 401903/2016-8; J.I.B.C. 308150/2016-3; MA 427700/2018-3, 310683/2017-3, 473002/2013-2. This study was financed in part by the Coordenação de Aperfeiaçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and the National Institute of Science and Technology of the e-Universe project (INCT do e-Universo, CNPq grant 465376/2014-2). GBR acknowledges CAPES-FAPERJ/PAPDRJ grant E26/203.173/2016, MA FAPERJ grant E-26/111.488/2013 and ARGJr FAPESP grant 2018/11239-8. E.F.-V. acknowledges support from the 2017 Preeminent Postdoctoral Program (P3) at UCF. C.K., R.S., A.F-T., and G.M. have been supported by the K-125015 and GINOP-2.3.2-15-2016-00003 grants of the Hungarian National Research, Development and Innovation Office (NKFIH), Hungary. G.M. was also supported by the Hungarian National Research, Development and Innovation Office (NKFIH) grant PD-128 360. R.K. and T.P. were supported by the VEGA 2/0031/18 grant

The distribution of standard deviations applied to high throughput screening

High throughput screening (HTS) assesses compound libraries for “activity” using target assays. A subset of HTS data contains a large number of sample measurements replicated a small number of times providing an opportunity to introduce the distribution of standard deviations (DSD). Applying the DSD to some HTS data sets revealed signs of bias in some of the data and discovered a sub-population of compounds exhibiting high variability which may be difficult to screen. In the data examined, 21% of 1189 such compounds were pan-assay interference compounds. This proportion reached 57% for the most closely related compounds within the sub-population. Using the DSD, large HTS data sets can be modelled in many cases as two distributions: a large group of nearly normally distributed “inactive” compounds and a residual distribution of “active” compounds. The latter were not normally distributed, overlapped inactive distributions – on both sides –, and were larger than typically assumed. As such, a large number of compounds are being misclassified as “inactive” or are invisible to current methods which could become the next generation of drugs. Although applied here to HTS, it is applicable to data sets with a large number of samples measured a small number of times