Hohlraum Reheating from Burning NIF Implosions.

As fusion experiments at the National Ignition Facility (NIF) approach and exceed breakeven, energy from the burning capsule is predicted to couple to the gold walls and reheat the hohlraum. On December 5, 2022, experiment N221204 exceeded target breakeven, historically achieving 3.15 MJ of fusion energy from 2.05 MJ of laser drive; for the first time, energy from the igniting capsule reheated the hohlraum beyond the peak laser-driven radiation temperature of 313 eV to a peak of 350 eV, in less than half a nanosecond. This reheating effect has now been unambiguously observed by the two independent Dante calorimeter systems across multiple experiments, and is shown to result from reheating of the remnant tungsten-doped ablator by the exploding core, which is heated by alpha deposition.

Computed Analysis of Retinal Vascular Growth After Bevacizumab Treatment of Retinopathy of Prematurity Until Age 3 Years.

PURPOSE: Premature infants, after anti-vascular endothelial growth factor injections for retinopathy of prematurity, have persistent peripheral avascular retina (PAR). PAR is ablated with laser; however, physiologic growth of the retinal vasculature in the long term has not been measured. The purposes of this study were to measure retinal vessel growth after treatment with intravitreal bevacizumab (IVB) for retinopathy of prematurity, using serial fluorescein angiography (FA), until age 3 years, and to assess the timing for providing laser ablation in PAR. METHODS: Data from an observational, longitudinal clinical study were collected. Angiographic images of eyes treated with IVB were included; imaging data from laser photocoagulation were excluded. All eyes underwent initial examination under general anesthesia with FA and photographic imaging. The retinal vessel length was measured from the temporal margin of the optic disc passing through the foveal center, and the lengths at subsequent FA were compared. To compare the changes in retinal vessel length over time in individual eyes, a paired-sample t test was performed. FINDINGS: FA images from 70 eyes (35 infants) treated with IVB were available. A total of 150 FA images were available for review; data from 125 images of good quality were used for analysis. The mean postmenstrual ages (PMAs) at first, second, third, and fourth FA were 66.2, 100.9, 135.1, and 180.7 weeks, respectively. The mean retinal vessel length was 14.177 mm at first FA and 13.199 mm at fourth FA (PMA range, 42...234 weeks). Retinal vascular lengths of individual eyes compared over time showed no statistically significant growth from the first FA to age 3 years. The changes in retinal vessel length from first to second FA were -0.117 ± 0.79 mm (p = 0.42; n = 30); from first to third FA, +0.060 ± 0.85 mm (p = 0.79; n = 15); and first to fourth FA, -0.404 ± 1.32 mm (p = 0.45; n = 7). IMPLICATIONS: Beyond 65 weeks' PMA, no meaningful retinal vascular growth occurred after IVB up to age 3 years, guiding the timing for physicians if laser photocoagulation is being considered. Future studies are needed to address retinal growth changes in the growing eyes of infants.

Tunable and state-preserving frequency conversion of single photons in hydrogen.

In modern quantum technologies, preservation of the photon statistics of quantum optical states upon frequency conversion holds the key to the viable implementation of quantum networks, which often require interfacing of several subsystems operating in widely different spectral regions. Most current approaches offer only very small frequency shifts and limited tunability, while suffering from high insertion loss and Raman noise originating in the materials used. We introduce a route to quantum-correlation-preserving frequency conversion using hydrogen-filled antiresonant-reflecting photonic crystal fibers. Transient optical phonons generated by stimulated Raman scattering enable selective frequency up-conversion by 125 terahertz of the idler photon of an entangled pair, with efficiencies up to 70%. This threshold-less molecular modulation process preserves quantum correlations, making it ideal for applications in quantum information.

Interpretable functional specialization emerges in deep convolutional networks trained on brain signals.

Objective.Functional specialization is fundamental to neural information processing. Here, we study whether and how functional specialization emerges in artificial deep convolutional neural networks (CNNs) during a brain-computer interfacing (BCI) task.Approach.We trained CNNs to predict hand movement speed from intracranial electroencephalography (iEEG) and delineated how units across the different CNN hidden layers learned to represent the iEEG signal.Main results.We show that distinct, functionally interpretable neural populations emerged as a result of the training process. While some units became sensitive to either iEEG amplitude or phase, others showed bimodal behavior with significant sensitivity to both features. Pruning of highly sensitive units resulted in a steep drop of decoding accuracy not observed for pruning of less sensitive units, highlighting the functional relevance of the amplitude- and phase-specialized populations.Significance.We anticipate that emergent functional specialization as uncovered here will become a key concept in research towards interpretable deep learning for neuroscience and BCI applications.

Twist and strain tuning of third harmonic generation in glass nanostrand with two sub-wavelength hollow channels.

A major challenge in third harmonic generation and its converse, parametric down-conversion, is how to arrange phase matching between signals at ω and 3ω while maintaining a high nonlinear overlap. In this Letter, we present a design consisting of a nanostrand of glass with two hollow channels. The fundamental and third harmonic modal fields, enhanced in the region between the channels, have high nonlinear overlap, while the phase-matching wavelength can be coarse-tuned by gas pressure and fine-tuned by axial strain and mechanical twist, which, remarkably, have opposite effects. The ability to adjust the phase-matching condition may facilitate efficient generation of entangled photon triplets.

Lower serum adiponectin level is associated with lipodystrophy among HIV-infected men in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) study.

OBJECTIVES: Adiponectin levels are inversely related to cardiovascular risk and are low in diabetics and obese persons. We examined the association between adiponectin concentration and HIV-associated lipodystrophy, which remains unclear. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) was a prospective cohort study of HIV-infected adults conducted in four US cities. Lean body and fat masses were assessed using dual-energy X-ray absorptiometry scans. Using baseline data from 2004 to 2006, we defined lipodystrophy using a sex-specific fat mass ratio and performed cross-sectional analyses of associated risks using multivariable logistic regression. RESULTS: Among 440 male participants (median age 42 years; 68% non-Hispanic white; 88% prescribed combination antiretroviral therapy; median CD4 lymphocyte count 468 cells/µL; 76% with viral load < 400 HIV-1 RNA copies/mL; 5% diabetic; median body mass index 25 kg/m2 ), median concentrations of leptin and adiponectin were 3.04 ng/L [interquartile range (IQR) 1.77-5.43 ng/L] and 8005 µg/mL (IQR 4950-11 935 µg/mL), respectively. The prevalence of lipodystrophy was 14%. Lipodystrophy was significantly associated with increasing age [prevalence ratio (PR) 1.50; 95% confidence interval (CI) 1.10-2.06, per 10 years], adiponectin < 8005 µg/mL (PR 5.02; 95% CI 2.53-9.95), ever stavudine use (PR 2.26; 95% CI 1.36-3.75), CD4 cell count > 500 cells/µL (PR 2.59; 95% CI 1.46-4.61), viral load < 400 copies/mL (PR 3.98; 95% CI 1.25-12.6), highly sensitive C-reactive protein < 1.61 mg/L (PR 1.91; 95% CI 1.11-3.28) and smoking (PR 0.42; 95% CI 0.22-0.78). CONCLUSIONS: Among men in this HIV-infected cohort, the prevalence of lipodystrophy was similar to previous estimates for persons living with HIV, and was associated with lower adiponectin levels, potentially indicating increased cardiovascular disease risk.

Re-irradiation of recurrent glioblastoma as part of a sequential multimodality treatment concept.

PURPOSE: The aim of this retrospective study was to evaluate survival outcomes in well-performing, mainly, young patients receiving a sequence of all available therapeutic options for relapsed glioblastoma, including re-irradiation. METHODS: We performed a retrospective analysis of 27 patients irradiated twice for glioblastoma between 2008 and 2016. In the first line, all had surgical treatment of the tumor followed by radiotherapy with a total dose of 60 Gy and temozolomide. All re-irradiated patients were treated with a total dose of 36 Gy in 12 fractions. The endpoints were death from glioblastoma or any cause, and toxicity after re-irradiation. RESULTS: The median follow-up of survivors was 35.6 months. At the time of analysis, 25 patients had died. The median time between first and second radiotherapy was 18.9 months (6.1-58.4). Re-irradiation was performed at different time points of first, second and third progression. The median overall survival after first diagnosis was 39.2 months. Five years after first surgery, nearly 20% of the patients were alive. CONCLUSION: Carefully planned re-irradiation of the brain is a safe therapy for recurrent glioblastoma. Younger and well-performing patients benefit from all available therapy options. Every patient should be discussed in a multidisciplinary setting at each time point of tumor progression. Further prospective studies are needed to define the optimal time, dose and volume of re-irradiation.

Investigating hydrophilic and electrostatic properties of surfactants using retention on two mixed-mode liquid chromatographic columns.

In environmental risk assessment, it is essential to understand the relationship between molecular structure and fate and toxicity of organic contaminants. For surfactants, physico-chemical parameters which can reflect the interactions that determine surfactant behavior are not well defined and are therefore needed for the development of robust quantitative structure-activity relationships (QSAR). For the present study, we have measured HPLC retention times of several hydrocarbon and perfluorocarbon surfactant groups on a mixed-mode weak anion-exchange (WAX) and mixed-mode hydrophilic interaction liquid chromatography (HILIC) stationary phase. The nonionic alcohol ethoxylates are well retained on the HILIC column. Retention of anionic surfactants on the HILIC column is likely influenced by the degree of hydration of the surfactants and electrostatic repulsion from silanol groups. Less hydrated anionic surfactants (perfluoroalkyl carboxylates, perfluoroalkyl sulfonates and alkyl sulfates) show minimal hydrophilic interaction while other better hydrated anionic surfactants (alkyl carboxylates and alkyl sulfonates) are well retained. The retention mechanism of surfactants on both columns seems to be related to their degree of hydration, albeit expressed in different retention behavior: generally, retention on the WAX phase increases when retention on the HILIC phase decreases, and vice versa. The retention times from both columns were used to calculate retention factors (k') and these were subsequently used in calculating parameters that reflect the electrostatic property (kAX) and hydrophilic property (kHILIC) that determine the interaction between the hydrophilic part of the surfactant and the stationary phase. In further development of predictive models, we suggest the use of kAX for anionic surfactants and kHILIC for nonionic surfactants.

Solubility Constraints on Aquatic Ecotoxicity Testing of Anionic Surfactants.

In order to develop models that can predict the environmental behavior and effects of chemicals, reliable experimental data are needed. However, for anionic surfactants the number of ecotoxicity studies is still limited. The present study therefore aimed to determine the aquatic ecotoxicity of three classes of anionic surfactants. To this purpose we subjected daphnids (Daphnia magna) for 48 h to alkyl carboxylates (CxCO2-), alkyl sulfonates (CxSO3-), and alkyl sulfates (CxSO4-) with different carbon chain lengths (x). However, all surfactants with x > 11 showed less than 50% immobility at water solubility. Hence, EC50 values for only few surfactants could be gathered: C9CO2- (16 mg L-1), C11CO2- (0.8 mg L-1) and C11SO4- (13.5 mg L-1). Data from these compounds showed an increase in ecotoxicity with a factor 4.5 per addition of a hydrocarbon unit to the alkyl chain, and a factor 20 when replacing the sulfate head group by a carboxylate head group. Unfortunately, we could not test carboxylates with a broader variety of chain lengths because solubility limited the range of chain length that can be tested.

TGF-ß1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis.

Barrier dysfunction has been implicated in the pathophysiology of eosinophilic esophagitis (EoE). Transforming growth factor-ß1 (TGF-ß1), a potent pleiotropic molecule, is increased in EoE; however, no study has evaluated its influence on esophageal epithelial barrier. We hypothesized that TGF-ß1 regulates barrier dysfunction in EoE. We aimed to determine the role of TGF-ß1 in the epithelial barrier in models of EoE. To examine the impact of TGF-ß1 on esophageal barrier, immortalized human esophageal epithelial (EPC2-hTERT) cells were exposed to TGF-ß1 during the three-dimensional air-liquid interface (3D-ALI) model in vitro. TGF-ß1 exposure diminished EPC2-hTERT barrier function as measured by transepithelial electrical resistance (TEER) and 3 kDa Fluorescein isothiocyanate dextran paracellular flux (FITC Flux), and hematoxylin and eosin (H&E) assessment revealed prominent cellular separation. In analysis of epithelial barrier molecules, TGF-ß1 led to the specific reduction in expression of the tight-junction molecule, claudin-7 (CLDN7), and this was prevented by TGF-ß-receptor I inhibitor. Short hairpin ribonucleic acid (shRNA)-mediated CLDN7 knockdown diminished epithelial barrier function, whereas CLDN7 overexpression resulted in protection from TGF-ß1-mediated barrier dysfunction. In pediatric EoE biopsies CLDN7 expression was decreased and altered localization was observed with immunofluorescence analysis, and the TGF-ß1 downstream transcription factor, phosphorylated SMAD2/3 (pSMAD2/3), was increased. Our data suggest that TGF-ß1 participates in esophageal epithelial barrier dysfunction through CLDN7 dysregulation.

Antiretroviral nonadherence and condomless sex in the HIV Outpatient Study, USA, 2007-2014.

Effective antiretroviral therapy (ART) reduces plasma HIV RNA viral load (VL) to undetectable levels and its effectiveness depends on consistent adherence. Consistent adherence and use of safe sex practices may substantially decrease the risk of HIV transmission. We sought to explore the potential association between self-reported nonadherence to ART and engaging in unsafe sexual practices capable of transmitting HIV. Using clinical and audio computer-assisted self-interview data from the prospective HIV Outpatient Study from 2007 to 2014, we assessed the frequency of self-reported ART nonadherence during the three days prior to the survey among HIV-infected persons in care and factors associated with self-reported ART nonadherence. Of 1729 patients included in this analysis (median age = 48 years, 74.3% men who have sex with men), 17% were nonadherent, 15% had a detectable VL, and 42% reported condomless anal or vaginal sex in the past six months. In multivariable analysis, self-reported nonadherence was independently associated with younger age (adjusted odds ratio [aOR] 0.8 per additional ten years, [95% CI] 0.7-1.0), non-Hispanic black race/ethnicity (aOR 1.9; 95% CI 1.4-2.6 versus white), public health insurance (aOR 1.6, 95% CI 1.2-2.3 compared with private), survey date in 2011-2014 versus 2007-2010 (aOR 0.7, 95% CI 0.5-0.9), CD4 cell count ≥ 500 versus < 200 cells/mm3 (aOR 0.3, 95% CI 0.2-0.5), greater number of ART regimen doses (aOR 1.6, 95% CI 1.3-2.2), and binge drinking (aOR 1.4, 95% CI, 1.1-1.9). In this analysis, self-reported nonadherence was not associated with engaging in condomless sex.

Clinical characteristics of functional dyspepsia depending on chemosensitivity to capsaicin.

BACKGROUND: Augmented chemosensitivity to capsaicin has been demonstrated in approximately half of functional dyspepsia (FD) patients. AIM: We determined clinical characteristics of FD patients with and without chemical hypersensitivity at baseline and after capsaicin ingestion for 4 weeks. METHODS: N=49 outpatients with confirmed FD received an oral sensitivity test with 0.75 mg capsaicin at three occasions, before and after ingesting 0.25 mg capsaicin tid for 4 weeks. Symptomatic response to capsaicin allowed stratification to a capsaicin positive (chemosensitive) and a capsaicin negative (not chemosensitive) patient group. Symptom diaries were completed in the week before and during capsaicin ingestion. RESULTS: A total of 53% FD had a positive capsaicin test, Crohnbach alpha was 0.85. Basic clinical characteristics were comparable in capsaicin positive and negative FD, but median daily aggregate upper gastrointestinal symptoms scores were significantly higher in capsaicin positive (median: 9.4; 5.4/11.7) than in capsaicin negative patients (6.6; 4.1/8.1) (P<.05). After capsaicin ingestion, upper gastrointestinal symptoms scores were reduced by -3.3 (-4.9/-1.9; P<.001) in capsaicin positive and -2.6 (-3.8/-0.3; P<.05) in capsaicin negative patients. Lower abdominal symptoms were comparable in capsaicin positive and negative patients at baseline (NS). After capsaicin ingestion lower gastrointestinal symptoms scores were reduced by -1.0 (-1.8/-0.1; P<.05) in capsaicin positive but not significantly altered (-0.6; -1.7/+0.9; NS) in capsaicin negative patients. After long-term capsaicin ingestion, the capsaicin test turned negative in 53% of chemosensitive patients (P<.01). CONCLUSIONS: Differences in upper GI symptoms distinguished capsaicin positive and negative patients. Symptom improvement after long-term capsaicin ingestion was indirect proportional to the capsaicin test result.

The Validity of a New Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) for Evaluating Symptoms in the Clinical Setting.

BACKGROUND: The clinical assessments of patients with gastrointestinal symptoms can be time-consuming, and the symptoms captured during the consultation may be influenced by a variety of patient and non-patient factors. To facilitate standardized symptom assessment in the routine clinical setting, we developed the Structured Assessment of Gastrointestinal Symptom (SAGIS) instrument to precisely characterize symptoms in a routine clinical setting. AIMS: We aimed to validate SAGIS including its reliability, construct and discriminant validity, and utility in the clinical setting. METHODS: Development of the SAGIS consisted of initial interviews with patients referred for the diagnostic work-up of digestive symptoms and relevant complaints identified. The final instrument consisted of 22 items as well as questions on extra intestinal symptoms and was given to 1120 consecutive patients attending a gastroenterology clinic randomly split into derivation (n = 596) and validation datasets (n = 551). Discriminant validity along with test-retest reliability was assessed. The time taken to perform a clinical assessment with and without the SAGIS was recorded along with doctor satisfaction with this tool. RESULTS: Exploratory factor analysis conducted on the derivation sample suggested five symptom constructs labeled as abdominal pain/discomfort (seven items), gastroesophageal reflux disease/regurgitation symptoms (four items), nausea/vomiting (three items), diarrhea/incontinence (five items), and difficult defecation and constipation (2 items). Confirmatory factor analysis conducted on the validation sample supported the initially developed five-factor measurement model ([Formula: see text], p < 0.0001, χ 2/df = 4.6, CFI = 0.90, TLI = 0.88, RMSEA = 0.08). All symptom groups demonstrated differentiation between disease groups. The SAGIS was shown to be reliable over time and resulted in a 38% reduction of the time required for clinical assessment. CONCLUSIONS: The SAGIS instrument has excellent psychometric properties and supports the clinical assessment of and symptom-based categorization of patients with a wide spectrum of gastrointestinal symptoms.

Targeting granulocyte-macrophage colony-stimulating factor in epithelial and vascular remodeling in experimental eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated clinicopathologic disease of the esophagus characterized by an eosinophil-predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis, and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting granulocyte-macrophage colony-stimulating factor (GM-CSF; an agonist cytokine linked with eosinophil survival and activation) would be protective in a preclinical model of EoE. METHODS: Eosinophilic esophagitis-like esophageal inflammation was induced in the L2-IL5OXA EoE mouse model, and GM-CSF production was assessed by mRNA and protein analyses. Granulocyte-macrophage colony-stimulating factor-receptor-alpha expression patterns were examined by flow cytometric and immunofluorescence analysis. L2-IL5OXA EoE mice were treated with anti-GM-CSF neutralizing antibody or isotype control and assessed for histopathological indices of eosinophilia, epithelial hyperplasia, and angiogenesis by immunohistochemistry and RT-PCR. RESULTS: Significantly increased levels of esophageal GM-CSF expression was detected in the L2-IL5OXA mouse EoE model during active inflammation. Granulocyte-macrophage colony-stimulating factor-receptor-alpha was predominantly expressed on esophageal eosinophils during EoE, in addition to select cells within the lamina propria. Anti-GM-CSF neutralization in L2-IL5OXA EoE mice resulted in a significant diminution of epithelial eosinophilia in addition to basal cell hyperplasia and vascular remodeling. This treatment response was independent of effects on esophageal eosinophil maturation or activation. CONCLUSION: Granulocyte-macrophage colony-stimulating factor is a potential therapeutic target to reduce esophageal eosinophilia and remodeling.

Phenotyping of subjects for large scale studies on patients with IBS.

BACKGROUND: Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. PURPOSE: The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).

Regulatory T cell frequencies are increased in preterm infants with clinical early-onset sepsis.

The predisposition of preterm neonates to invasive infection is, as yet, incompletely understood. Regulatory T cells (Tregs ) are potential candidates for the ontogenetic control of immune activation and tissue damage in preterm infants. It was the aim of our study to characterize lymphocyte subsets and in particular CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) Tregs in peripheral blood of well-phenotyped preterm infants (n = 117; 23 + 0 - 36 + 6 weeks of gestational age) in the first 3 days of life in comparison to term infants and adults. We demonstrated a negative correlation of Treg frequencies and gestational age. Tregs were increased in blood samples of preterm infants compared to term infants and adults. Notably, we found an increased Treg frequency in preterm infants with clinical early-onset sepsis while cause of preterm delivery, e.g. chorioamnionitis, did not affect Treg frequencies. Our data suggest that Tregs apparently play an important role in maintaining maternal-fetal tolerance, which turns into an increased sepsis risk after preterm delivery. Functional analyses are needed in order to elucidate whether Tregs have potential as future target for diagnostics and therapeutics.

Designs for a quantum electron microscope.

One of the astounding consequences of quantum mechanics is that it allows the detection of a target using an incident probe, with only a low probability of interaction of the probe and the target. This 'quantum weirdness' could be applied in the field of electron microscopy to generate images of beam-sensitive specimens with substantially reduced damage to the specimen. A reduction of beam-induced damage to specimens is especially of great importance if it can enable imaging of biological specimens with atomic resolution. Following a recent suggestion that interaction-free measurements are possible with electrons, we now analyze the difficulties of actually building an atomic resolution interaction-free electron microscope, or "quantum electron microscope". A quantum electron microscope would require a number of unique components not found in conventional transmission electron microscopes. These components include a coherent electron beam-splitter or two-state-coupler, and a resonator structure to allow each electron to interrogate the specimen multiple times, thus supporting high success probabilities for interaction-free detection of the specimen. Different system designs are presented here, which are based on four different choices of two-state-couplers: a thin crystal, a grating mirror, a standing light wave and an electro-dynamical pseudopotential. Challenges for the detailed electron optical design are identified as future directions for development. While it is concluded that it should be possible to build an atomic resolution quantum electron microscope, we have also identified a number of hurdles to the development of such a microscope and further theoretical investigations that will be required to enable a complete interpretation of the images produced by such a microscope.