Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of the Pharmacokinetics of Raltegravir Given at 2 Doses of 400 mg by Swallowing Versus One Dose of 800 mg by Chewing in Healthy Volunteers: A Randomized, Open-Label, 2-Period, Single-Dose, Crossover Phase 1 Study

Background: The pharmacokinetics of raltegravir (RAL) in HIV patients is characterized by high interindividual and intraindividual variability. We documented previously that HIV patients taking RAL at 400 mg bid by chewing the tablets had significantly higher drug absorption and reduced pharmacokinetic variability than patients taking the drug by swallowing the tablets. This study extends our previous findings. Methods: An open-label, 2-period crossover study compared the pharmacokinetics of 2 doses of RAL given at 400 mg every 12 hours (that mimics a bid administration) by swallowing with 1 dose of 800 mg (that mimics a qd administration) by chewing the tablets in 12 healthy volunteers. RAL plasma concentrations were measured by a chromatographic method coupled with mass spectrometry. Results: Subjects taking RAL by chewing had significantly higher drug exposure (RAL area under the curve[AUC]0–24: 40722 ± 14843 versus 21753 ± 12229 ng·h/mL, P < 0.0001) and reduced pharmacokinetic variability compared with those taking the drug by swallowing the whole tablet, with no difference in the minimum RAL concentrations (RAL Cmin: 36 ± 23 versus 43 ± 23 ng/mL, P = 0.298). Subjects taking RAL by chewing the tablets had significantly higher drug absorption and reduced pharmacokinetic variability compared with those taking the drug by swallowing. No differences were observed in the minimum RAL concentrations. Conclusions: RAL at 800 mg once daily by chewing the tablets may represent a novel therapeutic option for the treatment of HIV being associated with higher drug absorption, reduced pharmacokinetic variability, and potentially better compliance compared with patients swallowing the 400-mg bid intact tablets.
Inflammatory bowel disease in young people: The case for transitional clinics

Background: The incidence of inflammatory bowel disease (IBD) is increasing among adolescents. In all, 25% of patients are diagnosed before the age of 16, when they are traditionally transferred from the pediatric to the adult service. Methods: We conducted a retrospective case‐controlled study to characterize patients treated in a novel transitional adolescent–young adult IBD clinic. This compared disease extent, radiation exposure, therapeutic strategy, and requirement for surgery in 100 adolescents with controls from our adult IBD clinic matched for disease duration. Results: The median (range) ages for the adolescent and adult population was 19 (16–28) and 43 (24–84), with a median age at diagnosis of 15 (3–26) and 39 (13–82) respectively (P < 0.001). Crohn's disease was significantly more common in the adolescents. Disease distribution was ileocolonic in 69% of adolescents and 28% of adults, restricted to the ileum in 20% of adolescents and 47% of adults, and colonic only in 11% and 22%, respectively. Upper gastrointestinal involvement occurred in 23% of adolescents, but was not seen in adults (P < 0.01). Total ulcerative colitis was seen in 67% of adolescents and 44% of adults (P < 0.01). Contrary to previous data adolescents did not receive more ionizing radiation than adults. Requirement for immunosuppressive therapy was higher in the adolescent group (53% versus 31%, respectively, P < 0.01). Likewise, 20% of adolescents had required biological therapy compared to only 8% in the adult cohort (P < 0.05). Conclusions: Gastroenterologists should recognize that IBD is more complex when presenting in adolescence and our data support the creation of specific adolescent transitional clinics. Inflamm Bowel Dis 2009
Towards CNN Map Compression for camera relocalisation

This paper presents a study on the use of Convolutional Neural Networks for camera relocalisation and its application to map compression. We follow state of the art visual relocalisation results and evaluate response to different data inputs -- namely, depth, grayscale, RGB, spatial position and combinations of these. We use a CNN map representation and introduce the notion of CNN map compression by using a smaller CNN architecture. We evaluate our proposal in a series of publicly available datasets. This formulation allows us to improve relocalisation accuracy by increasing the number of training trajectories while maintaining a constant-size CNN.
Tight binding modeling of two dimensional and quasi-two dimensional materials

TIGHT BINDING MODELING OF TWO DIMENSIONAL AND QUASI-TWO DIMENSIONAL MATERIALS Deepak Kumar Singh M.S. in Physics Advisor: Oğuz Gülseren September 2017 Since the advent of graphene, two-dimensional (2D) materials have consistently been studied owing to their exceptional electronic and optical properties. While graphene is completely two-dimensional in nature, its other analogues from the group IV A elements in the periodic table have been proven to have a low-buckled structure which adds up the exotic properties exhibited by them. The semiconductor industry is striving for such materials exhibiting exotic electronic, optical and mechanical properties. In this thesis work we are primarily working towards a generalized tightbinding (TB) model for the 2D family of group IV A elements. Graphene has been studied extensively and we have successfully reproduced its energy bandstructure accounting up to the third nearest neighbor contributions. The results have been checked extensively by performing simulations over a large set of available parameters and are found to be accurate. The other graphene analogues (viz; silicene, germanene and stanene) exhibiting a hexagonal 2D structure have been reported to have a buckling associated to them. We have analytically built up a TB model by considering the orbital projections along the bond length which accounts for the buckling in these 2D structures. Electronic band-structures have been reproduced and compared by taking into account the nearest neighbor and next-nearest neighbor contributions. Since these structures exhibit a Dirac like cone at the Dirac point and showing linear dispersion, study of electronic bandstructures in detail becomes indispensable. After the famous Kane and Mele paper on Quantum Spin Hall Effect in Graphene, condensed matter physicists have been looking for similar phenomena in other 2D materials. We have successfully included the spin-orbit coupling iii
MARTIN’S MAXIMUM AND DEFINABILITY IN H(א2)

In [6], we modified a coding device from [14] and the consistency proof of Martin’s Maximum from [3] to show that from a supercompact limit of supercompact cardinals one could force Martin’s Maximum to hold while the Pmax axiom (∗) fails. Here we modify that argument to prove a stronger fact, that Martin’s Maximum is consistent with the existence of a wellordering of the reals definable in H(א2) without parameters, from the same large cardinal hypothesis. In doing so we give a much simpler proof of the original result.
A Randomized, Double-Blind, Controlled Trial of Perioperative Administration of Gabapentin, Meloxicam and Their Combination for Spontaneous and Movement-Evoked Pain After Ambulatory Laparoscopic Cholecystectomy

BACKGROUND: Hysterectomy and spinal surgery inpatient trials suggest favorable interactions between cyclooxgenase-2 inhibitors and gabapentin/pregabalin on postoperative days 1–2. We present the first trial of meloxicam-gabapentin combination after outpatient laparoscopic cholecystectomy. METHODS: This was a randomized, double-blind trial comparing daily oral administration of 1) meloxicam 15 mg, 2) gabapentin 1200–1600 mg, and 3) a combination of the two starting 1 h before until 2 days after surgery. Primary outcomes included day of surgery spontaneous and movement-evoked pain. Secondary outcomes included pain on Days 1, 2, and 30, adverse effects, opioid consumption, spirometry, pain-related interference, hospital discharge time, return to work time, and patient satisfaction. RESULTS: On the day of surgery, 60-min rest pain (0–10 numerical rating scale ± sd) was significantly lower (P < 0.05) with gabapentin alone (2.0 ± 1.6) versus meloxicam alone (3.6 ± 2.1). Observed pain differences between the combination (2.9 ± 2.1) and gabapentin alone were fairly small in favor of gabapentin alone (P > 0.05). Secondary analyses indicated that nausea was significantly less frequent with the combination (24%) versus the single-drug meloxicam (57%) only. CONCLUSION: Although nausea was reduced with combination therapy, this trial provides little or no support for the combined use of meloxicam and gabapentin for pain relief on the day of surgery. This suggests that perioperative analgesic polypharmacy may not always be necessary or appropriate.
A Switch from Cycloheximide-Resistant Consolidated Memory to Cycloheximide-Sensitive Reconsolidation and Extinction in Drosophila

It is generally accepted that, after learning, memories stabilize over time and integrate into long-term memory (LTM) through the process of consolidation, which depends on de novo protein synthesis. Besides, studies on several species have shown that reactivation of already stabilized LTM can either make this memory labile and then restabilize it (a process called reconsolidation) or inhibit it (extinction). However, the identity of both processes and their interactions with consolidation are still under debate. Regarding memory stabilization, Drosophila offers a striking exception since, in this species, LTM is not the sole stable form of memory. Under specific learning conditions, anesthesia-resistant memory (ARM) can be formed through processes yet unknown but that are resistant to cycloheximide, a classical protein synthesis inhibitor that impairs LTM. Here, we took advantage of this dichotomy to ask whether both ARM and LTM could be extinguished and/or reconsolidated. We also studied whether two forms of memory extinction and reconsolidation exist in flies, as for memory stabilization. We show that either reconsolidation or extinction can be induced after olfactory conditioning in Drosophila, depending on the number of reactivations as in other species. Furthermore, regarding the effect of cycloheximide, the ARM/LTM dichotomy for stabilization does not apply to extinction and reconsolidation. Blocking protein synthesis interfered with both processes regardless of whether initial stabilization was sensitive (LTM) or not (ARM) to cycloheximide. These results thus show that Drosophila is a useful model to tackle these questions and that reconsolidation is not necessarily a mere repetition of consolidation.
MIMO Relaying Broadcast Channels With Linear Precoding and Quantized Channel State Information Feedback

Multi-antenna relaying has emerged as a promising technology to enhance the system performance in cellular networks. However, when precoding techniques are utilized to obtain multi-antenna gains, the system generally requires channel state information (CSI) at the transmitters. We consider a linear precoding scheme in a MIMO relaying broadcast channel with quantized CSI feedback from both two-hop links. With this scheme, each remote user feeds back its quantized CSI to the relay, and the relay sends back the quantized precoding information to the base station (BS). An upper bound on the rate loss due to quantized channel knowledge is first characterized. Then, in order to maintain the rate loss within a predetermined gap for growing SNRs, a strategy of scaling quantization quality of both two-hop links is proposed. It is revealed that the numbers of feedback bits of both links should scale linearly with the transmit power at the relay, while only the bit number of feedback from the relay to the BS needs to grow with the increasing transmit power at the BS. Numerical results are provided to verify the proposed strategy for feedback quality control.
A comparison of dynamic contrast‐enhanced CT and MR imaging‐derived measurements in patients with cervical cancer

This work is to compare the kinetic parameters derived from the DCE‐CT and ‐MR data of a group of 37 patients with cervical cancer. The modified Tofts model and the reference tissue method were applied to estimate kinetic parameters. In the MR kinetic analyses using the modified Tofts model for each patient data set, both the arterial input function (AIF) measured from DCE‐MR images and a population‐averaged AIF from the literature were applied to the analyses, while the measured AIF was used for the CT kinetic analysis. The kinetic parameters obtained from both modalities were compared. Significant moderate correlations were found in modified Tofts parameters [volume transfer constant(Ktrans) and rate constant (kep)] between CT and MR analysis for MR with the measured AIFs (R = 0·45, P<0·01 and R = 0·40, P<0·01 in high‐Ktrans region; R = 0·38, P<0·01 and R = 0·80, P<0·01 in low‐Ktrans region) as well as with the population‐averaged AIF (R = 0·59, P<0·01 and R = 0·62, P<0·01 in high‐Ktrans region; R = 0·50, P<0·01 and R = 0·63, P<0·01 in low‐Ktrans region), respectively. In addition, from the Bland–Altman plot analysis, it was found that the systematic biases (the mean difference) between the modalities were drastically reduced in magnitude by adopting the population‐averaged AIF for the MR analysis instead of the measured ones (from 51·5% to 18·9% for Ktrans and from 21·7% to 4·1% for kep in high‐Ktrans region; from 73·0% to 29·4% for Ktrans and from 63·4% to 24·5% for kep in low‐Ktrans region). The preliminary results showed the feasibility in the interchangeable use of the two imaging modalities in assessing cervical cancers.
Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients.

AIMS To investigate associations between novel human cytochrome P450 (CYP450) combinatory (multigene) and substrate-specific drug metabolism indices, and elements of metabolic syndrome, such as low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides and BMI, using physiogenomic analysis. METHODS CYP2C9, CYP2C19 and CYP2D6 genotypes and clinical data were obtained for 150 consecutive, consenting hospital admissions with a diagnosis of major depressive disorder and who were treated with psychotropic medications. Data analysis compared clinical measures of LDLc, HDLc, triglyceride and BMI with novel combinatory and substrate-specific CYP450 drug metabolism indices. RESULTS We found that a greater metabolic reserve index score is related to lower LDLc and higher HDLc, and that a greater metabolic alteration index score corresponds with higher LDLc and lower HLDc values. We also discovered that the sertraline drug-specific indices correlated with cholesterol and triglyceride values. CONCLUSIONS Overall, we demonstrated how a multigene approach to CYP450 genotype analysis yields more accurate and significant results than single-gene analyses. Ranking the individual with respect to the population represents a potential tool for assessing risk of dyslipidemia in major depressive disorder patients who are being treated with psychotropics. In addition, the drug-specific indices appear useful for modeling a variable of potential relevance to an individual's risk of drug-related dyslipidemia.
QUANTITATIVE DETERMINATION OF ARISTOLOCHIC ACID-DERIVED DNA ADDUCTS IN RATS USING 32P-POSTLABELING/POLYACRYLAMIDE GEL ELECTROPHORESIS ANALYSIS

Aristolochic acids (AA) are nephrotoxic and carcinogenic nitroaromatic compounds produced by the Aristolochiaceae family of plants. Ingestion of these phytotoxins by humans results in a syndrome known as AA nephropathy, characterized by renal tubulointerstitial fibrosis and upper urothelial cancer. After activation by cellular enzymes, AA I and II react with DNA to form covalent adducts and as such represent potential biomarkers for studies of AA toxicity. Using site-specifically modified oligodeoxynucleotides as standards, we have developed a method for quantifying 7-(deoxyadenosin-N6-yl) aristolactam-DNA or 7-(deoxyguanosin-N2-yl) aristolactam-DNA adducts in tissues of Wistar rats using an assay in which 32P-postlabeling techniques are coupled with nondenaturing polyacrylamide gel electrophoresis. The limit of detection with this technique is five adducts in 109 nucleotides for a 5-μg DNA sample. In contrast to previous reports, we find that the levels of AA adducts in renal tissues of Wistar rats treated p.o. with AA for 1 week with 5 mg/kg/day of AA I or AA II were much higher than that in the forestomach. Highest adduct levels were observed in rats treated with AA II, suggesting that this compound may be more genotoxic than AA I. Treatment of rats with aristolactam I, an end-product of AA I metabolism, resulted in a much lower level of adduction. This study establishes the feasibility of using AA-DNA adducts as intermediate biomarkers of exposure in studies of AA nephropathy and its associated urothelial cancer.
Evaluating Biomarkers in Melanoma

The incidence of cutaneous melanoma has more than doubled over the last decades making it one of the fastest rising cancers worldwide. Improved awareness and early detection of malignant moles now permit earlier diagnosis aiming to decrease the likelihood of recurrence. However, it is difficult to identify those patients initially diagnosed with localized melanoma who subsequently develop metastatic disease. For this group, prognosis remains poor and clinical outcomes are variable and challenging to predict. Considerable efforts have focused on the search for novel prognostic tools, with numerous markers evaluated in the circulation and in tumor lesions. The most reliable predictors of patient outcome are the clinical and histological features of the primary tumor such as Breslow thickness, ulceration status, and mitotic rate. Elevated serum levels of the enzyme lactate dehydrogenase, likely to indicate active metastatic disease, are also routinely used to monitor patients. The emergence of novel immune and checkpoint antibody treatments for melanoma and increasing appreciation of key roles of the immune system in promoting or halting cancer progression have focused attention to immunological biomarkers. Validation of the most promising of these may have clinical applications in assisting prognosis, assessing endpoints in therapy, and monitoring responses during treatment.
The Effect of Steps to Promote Higher Levels of Farm Animal Welfare across the EU. Societal versus Animal Scientists’ Perceptions of Animal Welfare

Simple Summary We studied different EU production standards and initiatives to determine whether there is still room or not for further animal welfare improvement, and which should be the best way to achieve it. Many of the adopted measures in these standards and initiatives are scientifically supported, but other aspects that are equally important for animal welfare are not included in any of them. Animal welfare improvement should consider, for each country, those aspects actually benefiting animals, but also the social expectations within each country. Economic constraints might explain the gap between what society demands, and what farm animals actually need. Abstract Information about animal welfare standards and initiatives from eight European countries was collected, grouped, and compared to EU welfare standards to detect those aspects beyond minimum welfare levels demanded by EU welfare legislation. Literature was reviewed to determine the scientific relevance of standards and initiatives, and those aspects going beyond minimum EU standards. Standards and initiatives were assessed to determine their strengths and weaknesses regarding animal welfare. Attitudes of stakeholders in the improvement of animal welfare were determined through a Policy Delphi exercise. Social perception of animal welfare, economic implications of upraising welfare levels, and differences between countries were considered. Literature review revealed that on-farm space allowance, climate control, and environmental enrichment are relevant for all animal categories. Experts’ assessment revealed that on-farm prevention of thermal stress, air quality, and races and passageways’ design were not sufficiently included. Stakeholders considered that housing conditions are particularly relevant regarding animal welfare, and that animal-based and farm-level indicators are fundamental to monitor the progress of animal welfare. The most notable differences between what society offers and what farm animals are likely to need are related to transportation and space availability, with economic constraints being the most plausible explanation.
Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease

Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD).
Assessment of the mechanical properties of the musculoskeletal system using 2-D and 3-D very high frame rate ultrasound

One of the great challenges for understanding muscular diseases is to assess noninvasively the active and passive mechanical properties of the musculoskeletal system. In this paper we report the use of ultrafast ultrasound imaging to explore with a submillimeter resolution the behavior of the contracting tissues in vivo (biceps brachii). To image the contraction, which is a very brief phenomenon (<100 ms), a recently designed ultrasound scanner prototype able to take up to 6000 frames/s was used. A very high frame rate from 1000 to 2500 frames/s was used to image the cross section plane of the muscle (transverse to fibers) enabling us to catch in real time the muscle contraction during a transient electrostimulation. Tissue velocities were obtained from radiofrequency based speckle tracking techniques and their profiles are discussed with respect to electrostimulation intensities and pulse repetition frequencies for different volunteers. Three-dimensional (3-D) very high frame rate movies were also acquired by repeating the experiment for different acquisition planes while triggering the imaging system with the electrostimulation device. The reconstructed 3-D velocity field allows the full localization of the contracting fibers bundle. This ultrasound technique, referred to as echo mechanomyography, offers new perspectives for in vivo and in situ noninvasive muscle diagnosis of an active contractile tissue.