320 research outputs found
The reproductive potential of vitrifiedwarmed euploid embryos declines following repeated uterine transfers
Background Recurrent implantation failure (RIF) represents a vague clinical condition with an unclear diagnostic
challenge that lacks solid scientific underpinning. Although euploid embryos have demonstrated consistent
implantation capabilities across various age groups, a unanimous agreement regarding the advantages of
preimplantation genetic testing for aneuploidy (PGT-A) in managing RIF is absent. The ongoing discussion about
whether chromosomal aneuploidy in embryos significantly contributes to recurrent implantation failure remains
unsettled. Despite active discussions in recent times, a universally accepted characterization of recurrent implantation
failure remains elusive. We aimed in this study to measure the reproductive performance of vitrified-warmed euploid
embryos transferred to the uterus in successive cycles.
Methods This observational cohort study included women (n = 387) with an anatomically normal uterus who
underwent oocyte retrieval for PGT-A treatment with at least one biopsied blastocyst, between January 2017 and
December 2021 at a university-affiliated public fertility center. The procedures involved in this study included ICSI,
blastocyst culture, trophectoderm biopsy and comprehensive 24-chromosome analysis of preimplantation embryos
using Next Generation Sequencing (NGS). Women, who failed a vitrified-warmed euploid embryo transfer, had
successive blastocyst transfer cycles (FET) for a total of three using remaining cryopreserved euploid blastocysts from
the same oocyte retrieval cycle. The primary endpoints were sustained implantation rate (SIR) and live birth rate (LBR)
per vitrified-warmed single euploid embryo. The secondary endpoints were mean euploidy rate (m-ER) per cohort of
biopsied blastocysts from each patient, as well as pregnancy and miscarriage rates.
Results The mean age of the patient population was 33.4 years (95% CI 32.8–33.9). A total of 1,641 embryos derived
from the first oocyte retrieval cycle were biopsied and screened. We found no associations between the m-ER and
the number of previous failed IVF cycles among different ranges of maternal age at oocyte retrieval (P = 0.45). Pairwise
comparisons showed a significant decrease in the sustained implantation rate (44.7% vs. 30%; P = 0.01) and the
livebirth rate per single euploid blastocyst (37.1% vs. 25%; P = 0.02) between the 1st and 3rd FET. The cumulative SIR
and LBR after up to three successive single embryo transfers were 77.1% and 68.8%, respectively. We found that the live birth rate of the first vitrified-warmed euploid blastocyst transferred decreased significantly with the increasing
number of previously failed IVF attempts by categories (45.3% vs. 35.8% vs. 27.6%; P = 0.04). A comparable decrease in
sustained implantation rate was also observed but did not reach statistical significance (50% vs. 44.2 vs. 37.9%; P = NS).
Using a logistic regression model, we confirmed the presence of a negative association between the number of
previous IVF failed attempts and the live birth rate per embryo transfer cycle (OR = 0.76; 95% CI 0.62–0.94; P = 0.01).
Conclusions These findings are vital for enhancing patient counseling and refining management strategies
for individuals facing recurrent implantation failure. By tailoring interventions based on age and ovarian reserve,
healthcare professionals can offer more personalized guidance, potentially improving the overall success rates and
patient experiences in fertility treatments
Knowledge, Perception, Attitudes and Behavior on Influenza Immunization and the Determinants of Vaccination
BACKGROUND: We sought to determine the knowledge of, perception, attitudes, and behaviors toward influenza virus and immunization, and the determinants of vaccination among students, patients, and Healthcare Workers (HCWs) at the American University of Beirut and its affiliated Medical Center. METHODS: We conducted a cross-sectional study between October 2016 and January 2017 utilizing a self-administered questionnaire that was provided to 247 randomly selected adult participants. Data collected included socio-demographic characteristics, prior vaccination against influenza, knowledge, perception, attitudes, and behaviors toward influenza and influenza immunization. A multivariable regression model was used to evaluate for independent associations between the different variables and regular or yearly vaccination as a primary outcome. RESULTS: The overall survey response rate was 77%. A substantial proportion of respondents (47.4%) had never received the influenza vaccine. Only 10.2% of students, 19.1% of patients, and 35.6% of HCWs reported regular or yearly influenza vaccine uptake. HCWs had the lowest knowledge score about influenza and its vaccine despite high self-reported levels of knowledge. Barriers to vaccinations included lack of information (31%), fear of adverse effects (29%), and a perception of not being at risk (23%). Several factors were independently associated with regular or yearly vaccination uptake including having children (adjusted OR = 3.8; 95% CI 1.2-12.5), a "very good" self-reported level of knowledge (OR = 16.3; 95% CI 1.4-194.2) and being afraid of the consequences of influenza (OR = 0.2; 95% CI 0.1-0.6). CONCLUSION: Adherence rates with regular or yearly vaccination against influenza remain low across all study groups. We were able to identify predictors as well as barriers to vaccination. Future awareness and vaccination campaigns should specifically aim at correcting misconceptions about vaccination, particularly among HCWs, along with addressing the barriers to vaccination. Predictors of vaccination should be integrated in the design of future campaigns
Graphene doping to enhance flux pinning and supercurrent carrying ability in magnesium diboride superconductor
It has been shown that graphene doping is sufficient to lead to an
improvement in the critical current density - field performance (Jc(B)), with
little change in the transition temperature in MgB2. At 3.7 at% graphene doping
of MgB2 an optimal enhancement in Jc(B) was reached by a factor of 30 at 5 K
and 10 T, compared to the un-doped sample. The results suggested that effective
carbon substitutions by grapheme, 2D nature of grapheme and the strain effect
induced by difference thermal coefficient between single grapheme sheet and
MgB2 superconductor may play an important role in flux pinning enhancement
Phase Behavior of Polyelectrolyte Block Copolymers in Mixed Solvents
We have studied the phase behavior of the poly(n-butyl
acrylate)-b-poly(acrylic acid) block copolymer in a mixture of two miscible
solvents, water and tetrahydrofuran (THF). The techniques used to examine the
different polymers, structures and phases formed in mixed solvents were static
and dynamic light scattering, small-angle neutron scattering, nuclear magnetic
resonance and fluorescence microscopy. By lowering the water/THF mixing ratio
X, the sequence unimers, micron-sized droplets, polymeric micelles was
observed. The transition between unimers and the micron-sized droplets occurred
at X = 0.75, whereas the microstructuration into core-shell polymeric micelles
was effective below X = 0.4. At intermediate mixing ratios, a coexistence
between the micron-sized droplets and the polymeric micelles was observed.
Combining the different aforementioned techniques, it was concluded that the
droplet dispersion resulted from a solvent partitioning that was induced by the
hydrophobic blocks. Comparison of poly(n-butyl acrylate) homopolymers and
poly(n-butyl acrylate)-b-poly(acrylic acid) block copolymers suggested that the
droplets were rich in THF and concentrated in copolymers and that they were
stabilized by the hydrophilic poly(acrylic acid) moieties.Comment: 11 pages, 12 figures, to appear in Macromolecule
Design of the Pacemaker REmote Follow-up Evaluation and Review (PREFER) trial to assess the clinical value of the remote pacemaker interrogation in the management of pacemaker patients
Abstract
Background
Although pacemakers are primarily used for the treatment of bradycardia, diagnostic data available in current pacemakers allow them to be also used as sophisticated, continuous monitoring devices. Easy access to these stored data may assist clinicians in making diagnostic and therapeutic decisions sooner, thus avoiding potential long-term sequelae due to untreated clinical disorders. Internet-based remote device interrogation systems provide clinicians with frequent and complete access to stored data in pacemakers. In addition to monitoring device function, remote monitors may be a helpful tool in assisting physicians in the management of common arrhythmia disorders.
Methods
The Pacemaker REmote Follow-up Evaluation and Review (PREFER) trial is a prospective, randomized, parallel, unblinded, multicenter, open label clinical trial to determine the utility of remote pacemaker interrogation in the earlier diagnosis of clinically actionable events compared to the existing practice of transtelephonic monitoring. There have been 980 patients enrolled and randomized to receive pacemaker follow up with either remote interrogation using the Medtronic CareLink® Network (CareLink) versus the conventional method of transtelephonic monitoring (TTM) in addition to periodic in-person interrogation and programming evaluations. The purpose of this manuscript is to describe the design of the PREFER trial. The results, to be presented separately, will characterize the number of clinically actionable events as a result of pacemaker follow-up using remote interrogation instead of TTM.
Trial registration
ClinicalTrials.gov: NCT00294645.http://deepblue.lib.umich.edu/bitstream/2027.42/112561/1/13063_2008_Article_231.pd
Molecular characterization and clinical outcomes of pancreatic neuroendocrine tumors (pNENs) harboring PAK4-NAMPT alterations
Background: The mTOR inhibitor, Everolimus (EVE), is FDA-approved for the treatment of advanced PNENs on the basis of delay of progression. The RADIANT-3 trial showed an increase in PFS from 4.6 to 11 months compared to placebo with an ORR of only 5%. Prior studies suggest that targeting the aberrant expression of mTOR regulators p21 activated kinase 4 (PAK4) and nicotinamide adenine dinucleotide biosynthesis enzyme nicotinamide phosphoribosyltransferase (NAMPT) in PNENs sensitizes these tumors to EVE. To further qualify these observations, we queried a large real-world dataset of PNENs, characterizing the molecular and immune landscapes, as well as the clinical outcomes associated with aberrant PAK4 and NAMPT expression.
Methods: 294 cases of PNENs were analyzed using Next Generation Sequencing (NextSeq) and Whole Exome and Whole Transcriptome Sequencing (NovaSeq) at Caris Life Sciences (Phoenix, AZ). For our analyses, we stratified our study cohort into four groups based on the median expression of PAK4 and NAMPT: PAK4-low/NAMPT-low, PAK4-low/ NAMPT-high, PAK4-high/NAMPT-low and PAK4-high/NAMPT-high. Significance was determined using chi-square, Fisher-Exact or Mann-Whitney U, and p-values were adjusted for multiple comparisons (q , 0.05).
Results: High prevalence of mutations in PTEN (10.71% vs 1.18%; p \u3c 0.05, q \u3e 0.05), a tumor suppressor of the mTOR pathway and high expression of genes activated in response to mTOR activation such as SLC2A1 (3.07-fold), PFKP (3.32-fold), SCD (2.70-fold), MVK (2.92-fold) and G6PD (2.58-fold) were observed in PAK4-high/NAMPT-high compared to the PAK4-low/NAMPTlow tumors (all q , 0.05). A congruent enrichment of PI3K/AKT/mTOR and glycolysis pathways by single-sample gene set enrichment analysis was observed in these tumors (all q , 0.05). When querying the immune landscape, we observed enrichment in inflammatory response, IL6/JAK/STAT3, IL2/STAT5 signaling pathways and immune checkpoint genes such as PDCD1 (5.14-fold), CD274 (2.84-fold), PDCD1LG2 (2.44-fold), CD80 (3.00-fold), CD86 (2.82-fold), IDO1 (1.92-fold), LAG3 (3.09-fold), HAVCR2 (2.66-fold) and CTLA4 (4.49-fold) in the PAK4-high/NAMPT-high tumors (all q,0.05). Immune cell infiltration estimates revealed an increase in Neutrophils, NK cells and Tregs in the PAK4-high/NAMPT-high tumors (p \u3c 0.05, q \u3e 0.05).
Conclusions: Our study demonstrates that PAK4-high/NAMPT-high PNENs are associated with distinct molecular and immune profiles. While the dual blockade of PAK4 and NAMPT has been reported to enhance the efficacy of EVE in PNENs, whether such a blockade would enhance the efficacy of immunotherapeutics warrants further investigation
Graphene Photonics and Optoelectronics
The richness of optical and electronic properties of graphene attracts
enormous interest. Graphene has high mobility and optical transparency, in
addition to flexibility, robustness and environmental stability. So far, the
main focus has been on fundamental physics and electronic devices. However, we
believe its true potential to be in photonics and optoelectronics, where the
combination of its unique optical and electronic properties can be fully
exploited, even in the absence of a bandgap, and the linear dispersion of the
Dirac electrons enables ultra-wide-band tunability. The rise of graphene in
photonics and optoelectronics is shown by several recent results, ranging from
solar cells and light emitting devices, to touch screens, photodetectors and
ultrafast lasers. Here we review the state of the art in this emerging field.Comment: Review Nature Photonics, in pres
Post-graduation migration intentions of students of Lebanese medical schools: a survey study
<p>Abstract</p> <p>Background</p> <p>The international migration of physicians is a global public health problem. Lebanon is a source country with the highest emigration factor in the Middle East and North Africa and the 7th highest in the World. Given that residency training abroad is a critical step in the migration of physicians, the objective of this study was to survey students of Lebanese medical schools about their intentions to train abroad and their post training plans.</p> <p>Methods</p> <p>Our target population consisted of all students of Lebanese medical schools in the pre-final and final years of medical school. We developed the survey questionnaire based on the results of a qualitative study assessing the intentions and motives for students of Lebanese medical schools to train abroad. The questionnaire inquired about student's demographic and educational characteristics, intention to train abroad, the chosen country of abroad training, and post-training intention of returning to Lebanon.</p> <p>Results</p> <p>Of 576 eligible students, 425 participated (73.8% response rate). 406 (95.5%) respondents intended to travel abroad either for specialty training (330 (77.6%)) or subspecialty training (76 (17.9%)). Intention to train abroad was associated with being single compared with being married. The top 4 destination countries were the US (301(74.1%)), France (49 (12.1%)), the United Kingdom (31 (7.6%)) and Canada (17 (4.2%)). One hundred and two (25.1%) respondents intended to return to Lebanon directly after finishing training abroad; 259 (63.8%) intended to return to Lebanon after working abroad temporarily for a varying number or years; 43 (10.6%) intended to never return to Lebanon. The intention to stay indefinitely abroad was associated male sex and having a 2<sup>nd </sup>citizenship. It was inversely associated with being a student of one of the French affiliated medical schools and a plan to train in a surgical specialty.</p> <p>Conclusion</p> <p>An alarming percentage of students of Lebanese medical schools intend to migrate for post graduate training, mainly to the US. A minority intends to return directly to Lebanon after finishing training abroad.</p
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