955 research outputs found
The familial hypercholesterolaemia phenotype: Monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes
Familial Hypercholesterolaemia (FH) is a monogenic disorder characterised by high LDL-C concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Methods and Results Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory. LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8 genes were analysed by PCR amplification and Sanger sequencing. The 6-SNP LDL-C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH-causing mutation was found in 39% of patients (94% in LDLR, 5% APOB and 1% PCSK9), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management. This article is protected by copyright. All rights reserved
Record linkage under suboptimal conditions for data-intensive evaluation of primary care in Rio de Janeiro, Brazil
Background Linking Brazilian databases demands the development of algorithms and processes to deal with various challenges including the large size of the databases, the low number and poor quality of personal identifiers available to be compared (national security number not mandatory), and some characteristics of Brazilian names that make the linkage process prone to errors. This study aims to describe and evaluate the quality of the processes used to create an individual-linked database for data-intensive research on the impacts on health indicators of the expansion of primary care in Rio de Janeiro City, Brazil. Methods We created an individual-level dataset linking social benefits recipients, primary health care, hospital admission and mortality data. The databases were pre-processed, and we adopted a multiple approach strategy combining deterministic and probabilistic record linkage techniques, and an extensive clerical review of the potential matches. Relying on manual review as the gold standard, we estimated the false match (false-positive) proportion of each approach (deterministic, probabilistic, clerical review) and the missed match proportion (false-negative) of the clerical review approach. To assess the sensitivity (recall) to identifying social benefits recipients’ deaths, we used their vital status registered on the primary care database as the gold standard. Results In all linkage processes, the deterministic approach identified most of the matches. However, the proportion of matches identified in each approach varied. The false match proportion was around 1% or less in almost all approaches. The missed match proportion in the clerical review approach of all linkage processes were under 3%. We estimated a recall of 93.6% (95% CI 92.8–94.3) for the linkage between social benefits recipients and mortality data. Conclusion The adoption of a linkage strategy combining pre-processing routines, deterministic, and probabilistic strategies, as well as an extensive clerical review approach minimized linkage errors in the context of suboptimal data quality
Mansonella ozzardi in Amazonas, Brazil: prevalence and distribution in the municipality of Coari, in the middle Solimões River
The Interplay Between GUT and Flavour Symmetries in a Pati-Salam x S4 Model
Both Grand Unified symmetries and discrete flavour symmetries are appealing
ways to describe apparent structures in the gauge and flavour sectors of the
Standard Model. Both symmetries put constraints on the high energy behaviour of
the theory. This can give rise to unexpected interplay when building models
that possess both symmetries. We investigate on the possibility to combine a
Pati-Salam model with the discrete flavour symmetry that gives rise to
quark-lepton complementarity. Under appropriate assumptions at the GUT scale,
the model reproduces fermion masses and mixings both in the quark and in the
lepton sectors. We show that in particular the Higgs sector and the running
Yukawa couplings are strongly affected by the combined constraints of the Grand
Unified and family symmetries. This in turn reduces the phenomenologically
viable parameter space, with high energy mass scales confined to a small region
and some parameters in the neutrino sector slightly unnatural. In the allowed
regions, we can reproduce the quark masses and the CKM matrix. In the lepton
sector, we reproduce the charged lepton masses, including bottom-tau
unification and the Georgi-Jarlskog relation as well as the two known angles of
the PMNS matrix. The neutrino mass spectrum can present a normal or an inverse
hierarchy, and only allowing the neutrino parameters to spread into a range of
values between and , with .
Finally, our model suggests that the reactor mixing angle is close to its
current experimental bound.Comment: 62 pages, 4 figures; references added, version accepted for
publication in JHE
Air Travel Is Associated with Intracontinental Spread of Dengue Virus Serotypes 1–3 in Brazil
Dengue virus and its four serotypes (DENV-1 to DENV-4) infect 390 million people and are implicated in at least 25,000 deaths annually, with the largest disease burden in tropical and subtropical regions. We investigated the spatial dynamics of DENV-1, DENV-2 and DENV-3 in Brazil by applying a statistical framework to complete genome sequences. For all three serotypes, we estimated that the introduction of new lineages occurred within 7 to 10-year intervals. New lineages were most likely to be imported from the Caribbean region to the North and Northeast regions of Brazil, and then to disperse at a rate of approximately 0.5 km/day. Joint statistical analysis of evolutionary, epidemiological and ecological data indicates that aerial transportation of humans and/or vector mosquitoes, rather than Aedes aegypti infestation rates or geographical distances, determine dengue virus spread in Brazil
Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model
Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children
Brain serotonin depletion enhances the sodium appetite induced by sodium depletion or beta-adrenergic stimulation
Application of xylanases from Amazon Forest fungal species in bleaching of eucalyptus kraft pulps
Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy
We review HB stars in a broad astrophysical context, including both variable
and non-variable stars. A reassessment of the Oosterhoff dichotomy is
presented, which provides unprecedented detail regarding its origin and
systematics. We show that the Oosterhoff dichotomy and the distribution of
globular clusters (GCs) in the HB morphology-metallicity plane both exclude,
with high statistical significance, the possibility that the Galactic halo may
have formed from the accretion of dwarf galaxies resembling present-day Milky
Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the
second-parameter problem is presented. A technique is proposed to estimate the
HB types of extragalactic GCs on the basis of integrated far-UV photometry. The
relationship between the absolute V magnitude of the HB at the RR Lyrae level
and metallicity, as obtained on the basis of trigonometric parallax
measurements for the star RR Lyrae, is also revisited, giving a distance
modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are
studied. Finally, the conductive opacities used in evolutionary calculations of
low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and
Space Scienc
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