Abstract
Data on calving ease (CE) and birth, weaning weight (WW), and yearling weight (YW) were obtained from the American Simmental Association (ASA) and included pedigree and performance ...information on 11,640,735 animals. Our objective was to quantify differential response from selection for high CE vs. low birth weight (LBW) in first-calf Simmental heifers. We hypothesized that direct selection for CE should be used as the primary approach to reduce dystocia and mitigate losses in growth-related traits. WW and YW were adjusted to 205 and 365 d of age, respectively. Sire and maternal grandsire (co)variance components for CE, birth weight (BW), and 205-d weaning weight (205-d WW), and sire covariance components for 160-d postweaning gain (160-d gain) were estimated using a sire-maternal grandsire model. Direct and maternal expected progeny differences (EPD) for CE, BW, and 205-d WW and direct EPD for 160-d gain and 365-d yearling weight (365-d YW) for first-calf Simmental heifers population (465,710 animals) were estimated using a threshold-linear multivariate maternal animal model. This population was used to estimate genetic trends and as a selection pool (control) for various selection scenarios. Selection scenarios were high CE (HCE), LBW, the all-purpose selection index (API = −1.8 BW + 1.3 CE + 0.10 WW + 0.20 YW) of the ASA and its two derived subindices: (API1 = 1.3 CE + 0.20 YW) and (API2 = −1.8 BW + 0.20 YW), and lastly Dickerson’s selection index (DSI = −3.2 BW + YW). Data for each selection scenario were created by selecting sires with EPD greater than or equal to the average along with the top 75% of dams. Comparison between selection scenarios involved evaluating the direct and maternal genetic trends from these scenarios. Direct heritabilities for CE, BW, 205-d WW, 160-d gain, and 365-d YW of Simmental cattle were 0.23, 0.52, 0.28, 0.21, and 0.33, respectively. The single trait, HCE, selection scenario, as opposed to LBW, increased the intercept for CE by 57.7% and the slopes (P < 0.001) for BW, 205-d WW, 160-d gain, and 365-d YW by 27.9%, 37.5%, 16%, and 28%, respectively. Comparisons of various selection scenarios revealed that the CE-based selection scenarios (HCE, API, and API1) had a greater response for CE and growth traits.
The ecological conditions experienced by wildlife reservoirs affect infection dynamics and thus the distribution of pathogen excreted into the environment. This spatial and temporal distribution of ...shed pathogen has been hypothesised to shape risks of zoonotic spillover. However, few systems have data on both long‐term ecological conditions and pathogen excretion to advance mechanistic understanding and test environmental drivers of spillover risk. We here analyse three years of Hendra virus data from nine Australian flying fox roosts with covariates derived from long‐term studies of bat ecology. We show that the magnitude of winter pulses of viral excretion, previously considered idiosyncratic, are most pronounced after recent food shortages and in bat populations displaced to novel habitats. We further show that cumulative pathogen excretion over time is shaped by bat ecology and positively predicts spillover frequency. Our work emphasises the role of reservoir host ecology in shaping pathogen excretion and provides a new approach to estimate spillover risk.
We here analyse 3 years of Hendra virus data from nine Australian flying fox roosts with covariates derived from long‐term studies of bat ecology. We show that the magnitude of winter pulses of viral excretion, previously considered idiosyncratic, are most pronounced after recent food shortages and in bat populations displaced to novel habitats. We further show that cumulative pathogen excretion over time is shaped by bat ecology and positively predicts spillover frequency.
Frailty in older adults is a condition characterised by a loss or reduction in physiological reserve resulting in increased clinical vulnerability. However, evidence suggests that frailty may be ...modifiable, and identifying frail older people could help better target specific health care interventions and services.
This was a regional longitudinal study to develop a frailty index for older adults living in Canterbury New Zealand. Participants included 5586 community dwelling older people that had an interRAI Minimum Data Set (MDS-HC) Home Care assessment completed between 2008 and 2012. The outcome measures were mortality and entry into aged residential care (ARC), after five years.
Participants were aged between 65 and 101 (mean age was 82 years). The five-year mortality rate, including those who entered ARC, for this cohort was 67.1% (n = 3747). The relationship between the frailty index and both mortality and entry into ARC was significant (P < 0.001). At five years, 25.1% (n = 98) of people with a baseline frailty of < 0.1 had died compared with 28.2% (n = 22) of those with a frailty index of ≥0.5 (FS 5). Furthermore, 43.7% (n = 171) of people with a frailty index of < 0.1 were still living at home compared to 2.6% (n = 2) of those with a frailty index of ≥0.5.
A frailty index was created that predicts mortality, and admission into ARC. This index could help healthcare professionals and clinicians identify older people at risk of health decline and mortality, so that appropriate services and interventions may be put in place.
A Recombinant Vesicular Stomatitis Virus Ebola Vaccine Regules, Jason A; Beigel, John H; Paolino, Kristopher M ...
New England journal of medicine/The New England journal of medicine,
01/2017, Letnik:
376, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This final report updates preliminary data on an attenuated, replication-competent, recombinant vesicular stomatitis virus–based vaccine candidate designed to prevent Ebola virus disease. The results ...supported the safety and immunogenicity of up to two doses of the vaccine.
The worst Ebola virus disease (EVD) outbreak in recorded history has resulted in more than 28,000 cases and 11,000 reported deaths.
1
Although the primary strategy to stop the transmission of Ebola remains the identification and isolation of contacts and the use of appropriate personal protective equipment, the development of a safe and efficacious vaccine would provide an important public health tool. Numerous Ebola virus vaccine candidates are in preclinical development, and some have proceeded to human trials.
2
–
5
An Ebola virus vaccine candidate based on an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV) has shown promise in preclinical studies. The . . .
Planck 2018 results Aghanim, N.; Akrami, Y.; Ashdown, M. ...
Astronomy and astrophysics (Berlin),
09/2020, Letnik:
641
Journal Article
Recenzirano
Odprti dostop
The European Space Agency’s Planck satellite, which was dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre ...sky continuously between 12 August 2009 and 23 October 2013, producing deep, high-resolution, all-sky maps in nine frequency bands from 30 to 857 GHz. This paper presents the cosmological legacy of Planck , which currently provides our strongest constraints on the parameters of the standard cosmological model and some of the tightest limits available on deviations from that model. The 6-parameter ΛCDM model continues to provide an excellent fit to the cosmic microwave background data at high and low redshift, describing the cosmological information in over a billion map pixels with just six parameters. With 18 peaks in the temperature and polarization angular power spectra constrained well, Planck measures five of the six parameters to better than 1% (simultaneously), with the best-determined parameter ( θ * ) now known to 0.03%. We describe the multi-component sky as seen by Planck , the success of the ΛCDM model, and the connection to lower-redshift probes of structure formation. We also give a comprehensive summary of the major changes introduced in this 2018 release. The Planck data, alone and in combination with other probes, provide stringent constraints on our models of the early Universe and the large-scale structure within which all astrophysical objects form and evolve. We discuss some lessons learned from the Planck mission, and highlight areas ripe for further experimental advances.
A major barrier in the use of humanized mice as models of HIV-1 (HIV) infection is the inadequate generation of virus-specific antibody responses. Humanized DRAGA (hDRAGA) mice generate ...antigen-specific class switched antibodies to several pathogens, but whether they do so in HIV infection and the extent to which their secondary lymphoid tissues (sLT) support germinal center responses is unknown. hDRAGA mice were evaluated for their ability to support HIV replication, generate virus-specific antibody responses, develop splenocyte subsets, and organize sLT architecture. hDRAGA mice supported persistent HIV replication and developed modest levels of gp41-specific human IgM and IgG. Spleens from uninfected and HIV infected hDRAGA mice contained differentiated B and CD4
T cell subsets including germinal center (GC) B cells and T follicular helper cells (TFH); relative expansions of TFH and CD8
T cells, but not GC B cells, occurred in HIV-infected hDRAGA mice compared to uninfected animals. Immunofluorescent staining of spleen and mesenteric lymph node sections demonstrated atypical morphology. Most CD4
and CD8
T cells resided within CD20
areas. CD20
areas lacked canonical germinal centers, as defined by staining for IgD
Ki67
cells. No human follicular dendritic cells (FDC) were detected. Mouse FDC were distributed broadly throughout both CD20
and CD20
regions of sLT. HIV RNA particles were detected by
hybridization within CD20
areas and some co-localized with mouse FDC. Viral RNA
cells were more concentrated within CD20
compared to CD20
areas of sLT, but differences were diminished in spleen and eliminated in mesenteric lymph nodes when adjusted for CD4
cell frequency. Thus, hDRAGA mice recapitulated multiple aspects of HIV pathogenesis including HIV replication, relative expansions in TFH and CD8
T cells, and modest HIV-specific antibody production. Nevertheless, classical germinal center morphology in sLT was not observed, which may account for the inefficient expansion of GC B cells and generation of low titer human antibody responses to HIV-1 in this model.
Planck 2018 results Akrami, Y.; Ashdown, M.; Aumont, J. ...
Astronomy and astrophysics (Berlin),
09/2020, Letnik:
641
Journal Article
Recenzirano
Odprti dostop
We present full-sky maps of the cosmic microwave background (CMB) and polarized synchrotron and thermal dust emission, derived from the third set of
Planck
frequency maps. These products have ...significantly lower contamination from instrumental systematic effects than previous versions. The methodologies used to derive these maps follow closely those described in earlier papers, adopting four methods (
Commander
,
NILC
,
SEVEM
, and
SMICA
) to extract the CMB component, as well as three methods (
Commander
,
GNILC
, and
SMICA
) to extract astrophysical components. Our revised CMB temperature maps agree with corresponding products in the
Planck
2015 delivery, whereas the polarization maps exhibit significantly lower large-scale power, reflecting the improved data processing described in companion papers; however, the noise properties of the resulting data products are complicated, and the best available end-to-end simulations exhibit relative biases with respect to the data at the few percent level. Using these maps, we are for the first time able to fit the spectral index of thermal dust independently over 3° regions. We derive a conservative estimate of the mean spectral index of polarized thermal dust emission of
β
d
= 1.55 ± 0.05, where the uncertainty marginalizes both over all known systematic uncertainties and different estimation techniques. For polarized synchrotron emission, we find a mean spectral index of
β
s
= −3.1 ± 0.1, consistent with previously reported measurements. We note that the current data processing does not allow for construction of unbiased single-bolometer maps, and this limits our ability to extract CO emission and correlated components. The foreground results for intensity derived in this paper therefore do not supersede corresponding
Planck
2015 products. For polarization the new results supersede the corresponding 2015 products in all respects.
In this double-blind, randomized trial, vancomycin was added to cefazolin as surgical prophylaxis for arthroplasty. Surgical-site infections occurred in 4.5% of vancomycin recipients and 3.5% of ...placebo recipients.
Margins of wide local excisions in breast conserving surgery are tested through histology, which can delay results by days and lead to second operations. Detection of margin involvement ...intraoperatively would allow the removal of additional tissue during the same intervention. X-ray phase contrast imaging (XPCI) provides soft tissue sensitivity superior to conventional X-rays: we propose its use to detect margin involvement intraoperatively. We have developed a system that can perform phase-based computed tomography (CT) scans in minutes, used it to image 101 specimens approximately half of which contained neoplastic lesions, and compared results against those of a commercial system. Histological analysis was carried out on all specimens and used as the gold standard. XPCI-CT showed higher sensitivity (83%, 95% CI 69-92%) than conventional specimen imaging (32%, 95% CI 20-49%) for detection of lesions at margin, and comparable specificity (83%, 95% CI 70-92% vs 86%, 95% CI 73-93%). Within the limits of this study, in particular that specimens obtained from surplus tissue typically contain small lesions which makes detection more difficult for both methods, we believe it likely that the observed increase in sensitivity will lead to a comparable reduction in the number of re-operations.
Pathogen circulation among reservoir hosts is a precondition for zoonotic spillover. Unlike the acute, high morbidity infections typical in spillover hosts, infected reservoir hosts often exhibit low ...morbidity and mortality. Although it has been proposed that reservoir host infections may be persistent with recurrent episodes of shedding, direct evidence is often lacking. We construct a generalized SEIR (susceptible, exposed, infectious, recovered) framework encompassing 46 sub-models representing the full range of possible transitions among those four states of infection and immunity. We then use likelihood-based methods to fit these models to nine years of longitudinal data on henipavirus serology from a captive colony of Eidolon helvum bats in Ghana. We find that reinfection is necessary to explain observed dynamics; that acute infectious periods may be very short (hours to days); that immunity, if present, lasts about 1-2 years; and that recurring latent infection is likely. Although quantitative inference is sensitive to assumptions about serology, qualitative predictions are robust. Our novel approach helps clarify mechanisms of viral persistence and circulation in wild bats, including estimated ranges for key parameters such as the basic reproduction number and the duration of the infectious period. Our results inform how future field-based and experimental work could differentiate the processes of viral recurrence and reinfection in reservoir hosts. This article is part of the theme issue 'Dynamic and integrative approaches to understanding pathogen spillover'.
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