Simulating the vibrational quantum dynamics of molecules using photonics.

Advances in control techniques for vibrational quantum states in molecules present new challenges for modelling such systems, which could be amenable to quantum simulation methods. Here, by exploiting a natural mapping between vibrations in molecules and photons in waveguides, we demonstrate a reprogrammable photonic chip as a versatile simulation platform for a range of quantum dynamic behaviour in different molecules. We begin by simulating the time evolution of vibrational excitations in the harmonic approximation for several four-atom molecules, including H2CS, SO3, HNCO, HFHF, N4 and P4. We then simulate coherent and dephased energy transport in the simplest model of the peptide bond in proteins-N-methylacetamide-and simulate thermal relaxation and the effect of anharmonicities in H2O. Finally, we use multi-photon statistics with a feedback control algorithm to iteratively identify quantum states that increase a particular dissociation pathway of NH3. These methods point to powerful new simulation tools for molecular quantum dynamics and the field of femtochemistry.

A Peptide-Based Oscillator.

Living organisms are replete with rhythmic and oscillatory behavior at all levels, to the extent that oscillations have been termed as a defining attribute of life. Recent studies of synthetic oscillators that mimic such functions have shown decayed cycles in batch-mode reactions or sustained oscillatory kinetics under flow conditions. Considering the hypothesized functionality of peptides in early chemical evolution and their central role in current bio-nanotechnology, we now reveal a peptide-based oscillator. Oscillatory behavior was achieved by coupling coiled-coil-based replication processes as positive feedback to controlled initiation and inhibition pathways in a continuously stirred tank reactor (CSTR). Our results stress that assembly into the supramolecular structure and specific interactions with the replication substrates are crucial for oscillations. The replication-inhibition processes were first studied in batch mode, which produced a single damped cycle. Thereafter, combined experimental and theoretical characterization of the replication process in a CSTR under different flow and environmental (pH, redox) conditions demonstrated reasonably sustained oscillations. We propose that studies in this direction might pave the way to the design of robust oscillation networks that mimic the autonomous behavior of proteins in cells (e.g., in the cyanobacterial circadian clock) and hence hint at feasible pathways that accelerated the transition from simple peptides to extant enzymes.

Fournier's gangrene and fecal diversion. When, in which patients, and what type should I perform?

INTRODUCTION: Fournier's gangrene (FG) is a necrotizing fasciitis affecting the perineum and urogenital tissue. The mortality rate is high although early detection and aggressive debridement can reduce mortality by up to 16%. The prevalence of sequelae is very high and a colostomy is often necessary to control the perineal wound. MATERIAL AND METHODS: A retrospective study was carried out to recruit all patients operated on by the General Surgery and Urology Departments with a diagnosis of GF at the University Hospital over 22 years. Mortality, the Fournier gangrene severity index (FGSI), and fecal diversion (either surgical (colostomy) or straight (Flexi-seal)) are collected. RESULTS: A total of 149 patients met the inclusion criteria. FG's most frequent cause was a perianal abscess (107 patients-72%). Eighteen patients (12%) died of a specific cause of FG. Age (p = 0.014) and patients with an oncological history (p = 0.038) both were the only mortality risk factors for mortality according to logistic regression. Fifty patients required some form of fecal diversion in the postoperative period (32 colostomies and 18 Flexi-seal). Neither the use of postoperative fecal diversion (surgical or Flexi-seal) nor the timing of its use had any effect on postoperative mortality. CONCLUSIONS: One in eight patients died in the immediate postoperative period secondary to FG. Despite improved outcomes, 22% required a colostomy during admission. However, neither the performance of a colostomy nor the timing was associated with decreased FG-associated mortality. Non-invasive methods should be used first and surgical bowel diversion should be postponed as long as possible.

Efficient soliton self-frequency shift in hydrogen-filled hollow-core fiber.

We report a study of soliton self-frequency shifting in a hydrogen-filled hollow-core fiber. The combination of hydrogen and short 40-fs input pulses underlies clean and efficient generation of Raman solitons between 1080 and 1600 nm. With 240-nJ input pulses, the Raman soliton energy ranges from 110 to 20 nJ over that wavelength range, and the pulse duration is approximately 45 fs. In particular, 70-nJ and 42-fs pulses are generated at 1300 nm. Numerical simulations agree reasonably well with experiments and predict that microjoule-energy tunable pulses should be possible with higher-energy input pulses.

Dynamic properties of a self-replicating peptide network with inhibition.

In this paper, we report an open system consisting of three self-replicating peptides, in which peptide 1 inhibits the duplex template of peptide 2, peptide 2 inhibits duplex 3, and peptide 3 inhibits duplex 1 to complete the negative feedback loop. This interacting chemical network yields oscillations in the concentrations of all species over time and establishes a possible mechanism for pre-biotic chemical systems organization. The first focus of our analysis is the effect of altering rates of duplex formation and inhibition on oscillations. We then examine the autocatalytic rate constant in the symmetric and asymmetric cases.

A modified Ricker map and its bursting oscillations.

In our search to understand complex oscillation in discrete dynamic systems, we modify the Ricker map, where one parameter is also a dynamic variable. Using the bistable behavior of the fixed point solution, we analyze two response functions that characterize the change of the dynamic parameter. The 2D map sustains different types of burst oscillations that depend on the response functions. In either case, the parameter values yield a slow dynamic variable required to observe bursting-type oscillations.

Pediatric asthma treatment: What to do when international guideline recommendations do not agree.

BACKGROUND: There was a need for a solid asthma guideline in Mexico to update and unify asthma management. Because high-quality asthma guidelines exist worldwide, in which the latest evidence on asthma management is summarized, the ADAPTE approach allows for the development of a national asthma guideline based on evidence from already existing guidelines, adapted to national needs. OBJECTIVE: To fuse evidence from the best asthma guidelines and adapt it to local needs with the ADAPTE approach. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE) II asthma guidelines were evaluated by a core group to select 3 primary guidelines. For each step of asthma management, clinical questions were formulated and replied according to (1) evidence in the primary guidelines, (2) safety, (3) Cost, and (4) patient preference. The Guidelines Development Group, composed of a broad range of experts from medical specialties, primary care physicians, and methodologists, adjusted the draft questions and replies in several rounds of a Delphi process and 3 face-to-face meetings, taking into account the reality of the situation in Mexico. We present the results of the pediatric asthma treatment part. RESULTS: Selected primary guidelines are from the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN), Global Initiative for Asthma (GINA), and Spanish Guidelines on the Management of Asthma (GEMA) 2015, with 2016 updates. Recommendations or suggestions were made for asthma treatment in Mexico. In this article, the detailed analysis of the evidence present in the BTS/SIGN, GINA, and GEMA sections on the (non) pharmacologic treatment of pediatric asthma, education, and devices are presented for 2 age groups: children 5 years or younger and children 6 to 11 years old with asthma. CONCLUSION: For the pediatric treatment and patient education sections, applying the AGREE II and Delphi methods is useful to develop a scientifically sustained document, adjusted to the Mexican situation, as is the Mexican Guideline on Asthma.

Interferometer based on strongly coupled multi-core optical fiber for accurate vibration sensing.

We report on the use of a simple interferometer built with strongly-coupled core optical fiber for accurate vibration sensing. Our multi-core fiber (MCF) is designed to mode match a standard single-mode optical fiber (SMF). The interferometer consists of a low insertion loss SMF-MCF-SMF structure where only two super-modes interfere. The polymer coating of the MCF was structured and the interferometer was sandwiched between a flat piece and a V-groove. In this manner our device is highly sensitive to force with sensitivity reaching -4225 pm/N. To make the MCF interferometer sensitive to vibrations the flat piece was allowed to move, thus, its periodic movements exert cyclic localized pressure on the MCF which makes the interference pattern to shift periodically. Our sensors can be used to monitor vibrations in a broad frequency range with the advantage that the measurements are unaffected by temperature changes.

Miniature multicore optical fiber vibration sensor.

We demonstrate a compact and versatile interferometric vibration sensor that operates in reflection mode. To build the device, a short segment of symmetric strongly coupled multicore optical fiber (MCF) is fusion spliced to a single-mode optical fiber (SMF). One end of the MCF segment is cleaved and placed in a cantilever position. Due to the SMF-MCF configuration, only two supermodes are excited in the MCF. Vibrations induce cyclic bending of the MCF cantilever which results in periodic oscillations of the reflected interference spectrum. In our device, the MCF itself is the inertial mass. The frequency range where our device is sensitive can be easily tailored from a few hertz to several kilohertz through the cantilever dimensions.

Bistability and Bifurcation in Minimal Self-Replication and Nonenzymatic Catalytic Networks.

Bistability and bifurcation, found in a wide range of biochemical networks, are central to the proper function of living systems. We investigate herein recent model systems that show bistable behavior based on nonenzymatic self-replication reactions. Such models were used before to investigate catalytic growth, chemical logic operations, and additional processes of self-organization leading to complexification. By solving for their steady-state solutions by using various analytical and numerical methods, we analyze how and when these systems yield bistability and bifurcation and discover specific cases and conditions producing bistability. We demonstrate that the onset of bistability requires at least second-order catalysis and results from a mismatch between the various forward and reverse processes. Our findings may have far-reaching implications in understanding early evolutionary processes of complexification, emergence, and potentially the origin of life.

Effects of growth hormone treatment on growth plate, bone, and mineral metabolism of young rats with uremia induced by adenine.

BackgroundIn a model of growth retardation secondary to chronic kidney disease (CKD) induced by adenine, this study explores the effects of growth hormone (GH) therapy on growth plate and mineral metabolism.MethodsWeaning female rats receiving a 0.5% adenine diet during 21 days, untreated (AD) or treated with GH (ADGH) for 1 week, were compared with control rats receiving normal diet, either ad libitum or pair-fed with AD animals. AD and ADGH rats had similarly elevated serum concentrations of urea nitrogen, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23).ResultsUremia induced by adenine caused growth retardation and disturbed growth cartilage chondrocyte hypertrophy. We demonstrated marked expression of aquaporin 1 in the growth plate, but its immunohistochemical signal and the expression levels of other proteins potentially related with chondrocyte enlargement, such as Na-K-2Cl cotransporter, insulin-like growth factor 1 (IGF-1), and IGF-1 receptor, were not different among the four groups of rats. The distribution pattern of vascular endothelial growth factor was also similar. AD rats developed femur bone structure abnormalities analyzed by micro-computerized tomography.ConclusionGH treatment accelerated longitudinal growth velocity, stimulated the proliferation and enlargement of chondrocytes, and did not modify the elevated serum PTH or FGF23 concentrations or the abnormal bone structure.

Effects of growth hormone treatment on growth plate, bone, and mineral metabolism of young rats with uremia induced by adenine.

This corrects the article DOI: 10.1038/pr.2017.95.

Ultrasensitive vector bending sensor based on multicore optical fiber.

In this Letter, we demonstrate a compellingly simple directional bending sensor based on multicore optical fibers (MCF). The device operates in reflection mode and consists of a short segment of a three-core MCF that is fusion spliced at the distal end of a standard single mode optical fiber. The asymmetry of our MCF along with the high sensitivity of the supermodes of the MCF make the small bending on the MCF induce drastic changes in the supermodes, their excitation, and, consequently, on the reflected spectrum. Our MCF bending sensor was found to be highly sensitive (4094 pm/deg) to small bending angles. Moreover, it is capable of distinguishing multiple bending orientations.

The relationship between cognitive reserve and the clinical stage of HIV infection.

The objective of this study was to determine whether the effect of cognitive reserve (CR) on neuropsychological functioning differs according to the clinical stage of HIV infection. A sample of 34 HIV-positive individuals aged 23-49, with a minimum of 9 years of formal education, was assessed. Participants were grouped according to the Centers for Disease Control and Prevention's (CDC) clinical stages (A = 10, B = 16, C = 8). CR was calculated for each clinical stage group in accordance with estimates of premorbid IQ, years of education, and occupational attainment. The sum of these three variables was then transformed into z-scores. Individuals above the median were classified as having "High" CR (HCR), those below the median were classified as "Low" CR (LCR). Participants completed an evaluation of cognitive and executive functions based on selected, modified tasks from the HIV University of Miami Annotated Neuropsychological test in Spanish (HUMANS). Assessment included the following domains: attention, memory (visual, verbal, and working memory), executive functions (cognitive flexibility, switching), language (naming), and visual constructive skills (block design). HCR outperformed LCR in all cognitive domains. Comparison of HCR and LCR in each clinical stage revealed that the effect of CR was stronger in stage B than in stages A and C, suggesting that this effect does indeed vary among stages.

Chronic kidney disease induced by adenine: a suitable model of growth retardation in uremia.

Growth retardation is a major manifestation of chronic kidney disease (CKD) in pediatric patients. The involvement of the various pathogenic factors is difficult to evaluate in clinical studies. Here, we present an experimental model of adenine-induced CKD for the study of growth failure. Three groups (n = 10) of weaning female rats were studied: normal diet (control), 0.5% adenine diet (AD), and normal diet pair fed with AD (PF). After 21 days, serum urea nitrogen, creatinine, parathyroid hormone (PTH), weight and length gains, femur osseous front advance as an index of longitudinal growth rate, growth plate histomorphometry, chondrocyte proliferative activity, bone structure, aorta calcifications, and kidney histology were analyzed. Results are means ± SE. AD rats developed renal failure (serum urea nitrogen: 70 ± 6 mg/dl and creatinine: 0.6 ± 0.1 mg/dl) and secondary hyperparathyroidism (PTH: 480 ± 31 pg/ml). Growth retardation of AD rats was demonstrated by lower weight (AD rats: 63.3 ± 4.8 g, control rats: 112.6 ± 4.7 g, and PF rats: 60.0 ± 3.8 g) and length (AD rats: 7.2 ± 0.2 cm, control rats: 11.1 ± 0.3 cm, and PF rats: 8.1 ± 0.3 cm) gains as well as lower osseous front advances (AD rats: 141 ± 13 µm/day, control rats: 293 ± 16 µm/day, and PF rats: 251 ± 10 µm/day). The processes of chondrocyte maturation and proliferation were impaired in AD rats, as shown by lower growth plate terminal chondrocyte height (21.7 ± 2.3 vs. 26.2 ± 1.9 and 23.9 ± 1.3 µm in control and PF rats) and proliferative activity index (AD rats: 30 ± 2%, control rats: 38 ± 2%, and PF rats: 42 ± 3%). The bone primary spongiosa structure of AD rats was markedly disorganized. In conclusion, adenine-induced CKD in young rats is associated with growth retardation and disturbed endochondral ossification. This animal protocol may be a useful new experimental model to study growth in CKD.

10 Spatial mode transmission using low differential mode delay 6-LP fiber using all-fiber photonic lanterns.

To unlock the cost benefits of space division multiplexing transmission systems, higher spatial multiplicity is required. Here, we investigate a potential route to increasing the number of spatial mode channels within a single core few-mode fiber. Key for longer transmission distances and low computational complexity is the fabrication of fibers with low differential mode group delays. As such in this work, we combine wavelength and mode-division multiplexed transmission over a 4.45 km low-DMGD 6-LP-mode fiber by employing low-loss all-fiber 10-port photonic lanterns to couple light in and out of the fiber. Hence, a minimum DMGD of 0.2 ns (maximum 0.357 ns) is measured after 4.45 km. Instrumental to the multi-mode transmission system is the employed time-domain-SDM receiver, allowing 10 spatial mode channels (over both polarizations) to be captured using only 3 coherent receivers and real-time oscilloscopes in comparison with 10 for conventional methods. The spatial channels were unraveled using 20 × 20 multiple-input multiple-output digital signal processing. By employing a novel round-robin encoding technique, stable performance over a long measurement period demonstrates the feasibility of 10x increase in single-core multi-mode transmission.

Monitoring lipase/esterase activity by stopped flow in a sequential injection analysis system using p-nitrophenyl butyrate.

Lipases and esterases are biocatalysts used at the laboratory and industrial level. To obtain the maximum yield in a bioprocess, it is important to measure key variables, such as enzymatic activity. The conventional method for monitoring hydrolytic activity is to take out a sample from the bioreactor to be analyzed off-line at the laboratory. The disadvantage of this approach is the long time required to recover the information from the process, hindering the possibility to develop control systems. New strategies to monitor lipase/esterase activity are necessary. In this context and in the first approach, we proposed a lab-made sequential injection analysis system to analyze off-line samples from shake flasks. Lipase/esterase activity was determined using p-nitrophenyl butyrate as the substrate. The sequential injection analysis allowed us to measure the hydrolytic activity from a sample without dilution in a linear range from 0.05-1.60 U/mL, with the capability to reach sample dilutions up to 1000 times, a sampling frequency of five samples/h, with a kinetic reaction of 5 min and a relative standard deviation of 8.75%. The results are promising to monitor lipase/esterase activity in real time, in which optimization and control strategies can be designed.

Optimization of multicore fiber for high-temperature sensing.

We demonstrate a novel high-temperature sensor using multicore fiber (MCF) spliced between two single-mode fibers. Launching light into such fiber chains creates a supermode interference pattern in the MCF that translates into a periodic modulation in the transmission spectrum. The spectrum shifts with changes in temperature and can be easily monitored in real time. This device is simple to fabricate and has been experimentally shown to operate at temperatures up to 1000°C in a very stable manner. Through simulation, we have optimized the multicore fiber design for sharp spectral features and high overall transmission in the optical communications window. Comparison between the experiment and the simulation has also allowed determination of the thermo-optic coefficient of the MCF as a function of temperature.

Diagnostic Utility of the International HIV Dementia Scale for HIV-Associated Neurocognitive Impairment and Disorder in South Africa.

Studies in sub-Saharan Africa indicate that most HIV seropositive persons have HIV-associated neurocognitive disorder (HAND). HAND diagnosis is facilitated by specific screening. Seventy participants were recruited from an HIV voluntary counseling and testing clinic in Durban, South Africa. The diagnostic utility of the International HIV Dementia Scale (IHDS) was analyzed using a receiver operating characteristic (ROC) model. The ROC analysis comparing any HAND diagnosis (based on two neuropsychological tests) versus no diagnosis was statistically significant, with an optimal cut-off score of 10.5, sensitivity of 69%, and specificity of 74%. Sensitivity of the IHDS was highest for HIV-associated dementia.

Current status of circulating protein biomarkers to aid the early detection of lung cancer.

Considerable efforts have been undertaken to produce an effective screening method to reduce lung cancer mortality. Imaging tools such as low-dose computed tomography has shown an increase in the detection of early disease and a reduction in the rate of death. This screening modality has, however, several limitations, such as overdiagnosis and a high rate of false positives. Therefore, new screening methods, such as the use of circulating protein biomarkers, have emerged as an option that could complement imaging studies. In this review, current imaging techniques applied to lung cancer screening protocols are presented, as well as up-to-date status of circulating protein biomarker panels that may improve lung cancer diagnosis. Additionally, diverse statistical and artificial intelligence tools applied to the design and optimization of these panels are discussed along with the presentation of two commercially available blood tests recently developed to help detect lung cancer early.