Waveguide-integrated silicon T centres.

The performance of modular, networked quantum technologies will be strongly dependent upon the quality of their quantum light-matter interconnects. Solid-state colour centres, and in particular T centres in silicon, offer competitive technological and commercial advantages as the basis for quantum networking technologies and distributed quantum computing. These newly rediscovered silicon defects offer direct telecommunications-band photonic emission, long-lived electron and nuclear spin qubits, and proven native integration into industry-standard, CMOS-compatible, silicon-on-insulator (SOI) photonic chips at scale. Here we demonstrate further levels of integration by characterizing T centre spin ensembles in single-mode waveguides in SOI. In addition to measuring long spin T1 times, we report on the integrated centres' optical properties. We find that the narrow homogeneous linewidth of these waveguide-integrated emitters is already sufficiently low to predict the future success of remote spin-entangling protocols with only modest cavity Purcell enhancements. We show that further improvements may still be possible by measuring nearly lifetime-limited homogeneous linewidths in isotopically pure bulk crystals. In each case the measured linewidths are more than an order of magnitude lower than previously reported and further support the view that high-performance, large-scale distributed quantum technologies based upon T centres in silicon may be attainable in the near term.

Windows of sensitivity to toxic chemicals in the development of the endocrine system: an analysis of ATSDR's toxicological profile database.

This review utilizes the robust database of literature contained in toxicological profiles developed by the Agency for Toxic Substances and Disease Registry. The aim was to use this database to identify developmental toxicity studies reporting alterations in hormone levels in the developing fetus and offspring and identify windows of sensitivity. We identified 74 oral exposure studies in rats that provided relevant information on 30 chemicals from 21 profiles. Most studies located provided information on thyroid hormones, with fewer studies on anterior pituitary, adrenal medulla, ovaries, and testes. No studies pertaining to hormones of the posterior pituitary, pancreas, or adrenal cortex were located. The results demonstrate that development of the endocrine system may be affected by exposure to environmental contaminants at many different points, including gestational and/or lactational exposure. Moreover, this review demonstrates the need for more developmental toxicity studies focused on the endocrine system and specifically alterations in hormone levels.

Chemical interactions and mixtures in public health risk assessment: An analysis of ATSDR's interaction profile database.

The Agency for Toxic Substances and Disease Registry (ATSDR) develops interaction profiles using binary weight of evidence (BINWOE) methodology to determine interaction directions of common environmental mixtures. We collected direction of interactions, BINWOE score determination, and BINWOE score confidence rating from 13 interaction profiles along with toxicodynamic and toxicokinetic influences on interaction direction. By doing so, we quantified the 1) direction of interaction and indeterminate evaluations; 2) characterized confidence in the BINWOE determinations; and 3) quantified toxicokinetic/toxicodynamic, and other influences on projected BINWOE interaction directions. Thirty-nine percent (130/336) of the attempts to make a BINWOE were indeterminate due to no interaction data or inadequate or conflicting evidence. Out of remaining BINWOEs, 25% were additive, 9% were greater-than-additive, and 27% were less-than-additive interactions. Fifty-five percent of BINWOEs were explained by toxicokinetic interactions, 12% and 5% were explained by toxicodynamic and other explanations, respectively. High quality mixture toxicology in vivo studies along with mixture in vitro and in silico studies will lead to greater confidence in interaction directions and influences. Limitations for interpretation of the data were also included.

Per- and polyfluoroalkyl mixtures toxicity assessment "Proof-of-Concept" illustration for the hazard index approach.

The 2018 ATSDR mixture framework recommends three approaches including the hazard index (HI) for environmental mixture toxicity assessment. Per- and polyfluoroalkyls (PFAS) are found in our environment and general populations. Recent experimental mixture toxicity studies of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and an assessment of 17 PFAS indicate the use of additivity for their joint toxicity assessment. The aim of this investigation was to detail the stepwise procedures and examine the extent and use of the HI approach for PFAS mixture assessment. Using estimated general public lifetime exposures (high, medium, and low), binary mixtures of PFOS and PFOA yielded, respectively, hazard indices (HIs) of 30.67, 8.33, and 3.63 for developmental toxicity; 10.67, 5.04, and 2.34 for immunological toxicity; 3.57, 1.68, and 0.78 for endocrine toxicity; 4.51, 1.73, and 0.79 for hepatic toxicity; and 15.08, 2.29, and 0.88 for reproductive toxicity. A heterogeneous mixture of PFOA, PFAS, dioxin (CDD), and polybrominated compounds (PBDE) for high exposure scenario yielded HIs of 30.99 for developmental, 10.77 for immunological, 3.64 for endocrine, 4.61 for hepatic, and 17.36 for reproductive effects. The HI values are used as a screening tool; the potential concern for exposures rises as HI values increase. For HI values >1, a follow-up including further analysis of specific exposures, use of internal dosimetry, and uncertainty factors is conducted before recommending appropriate actions. The HI approach appears suitable to address present-day PFAS public health concerns for initial assessment of multiple health effects, until further insights are gained into their mechanistic toxicology.The findings and conclusions in this article are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry.

A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Implementation of the accelerated care of torsion pathway: a quality improvement initiative for testicular torsion.

BACKGROUND: Timely diagnosis and management of testicular torsion is of paramount importance. Furthermore, time to surgical intervention is a benchmark for the quality of care provided by pediatric urologists included in US News and World Report (USNWR) methodology. OBJECTIVE: We sought to optimize management of acute testicular torsion at a single institution by decreasing time from presentation to definitive management through the creation and implementation of a clinical care pathway (accelerated care of torsion or ACT) for acute testicular torsion in a 2-year period. STUDY DESIGN: Multidisciplinary process mapping involving the emergency department (ED), radiology, anesthesiology, peri-operative services, and operating room (OR) teams resulted in development of the ACT pathway with the goal of achieving surgical intervention within 4 h of arrival at our institution. The accelerated care of torsion pathway was implemented in April 2016. Thirty-eight consecutive acute torsion cases were then prospectively evaluated from April 2016 to April 2018. For process measures, we recorded triage to OR times and mode of presentation. For outcome measures, we examined orchiectomy rates. We retrospectively reviewed 97 cases of acute torsion from 2004 to 2016 as a control. RESULTS: Time from ED triage to OR start decreased from a median 196 min (interquartile range [IQR] 137-249 min) to 127 min (IQR 100-148 min; P < 0.0001) for all cases of acute torsion. In the control group, 72% of cases met the USNWR criteria for acute treatment of torsion. After ACT implementation, 100% of cases reached the OR within the 240 min time frame. Orchiectomy rates were performed in 24% of control cases vs 30% after ACT implementation (P = NS). Survival curve analysis demonstrated no significant difference in probability of testis salvage before or after implementation of the ACT pathway. DISCUSSION: In agreement with similar studies, despite a significant reduction in triage to OR times, the orchiectomy rate approached 30%. This outcome did not significantly improve after implementation of the ACT pathway. Overall ischemia time was a more important determinant of testis salvage. Study limitations include limited patient follow-up to assess testis atrophy. CONCLUSIONS: The multidisciplinary creation and implementation of a clinical pathway for the care of acute testis torsion has significantly decreased the time from ED to OR in our institution. However, overall orchiectomy rate was not significantly affected.

Association between urodynamic parameters and urine neutrophil gelatinase-associated lipocalin concentrations in children with neuropathic bladders.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of acute kidney injury, and has been shown to be a sensitive marker of renal damage in urinary tract obstruction. Children with neurogenic bladders are at risk of renal damage as a result of increased pressure within the urinary system. A marker of upper tract deterioration in this population would be useful to guide management. OBJECTIVE: The aim of the study is to compare urinary NGAL (uNGAL) concentrations between children who have elevated and normal detrusor pressure and between those with low and normal compliance, on urodynamics. STUDY DESIGN: This is a cross-sectional study of children with neurogenic bladder who underwent routine urodynamics from August 2015 to March 2016. Patients with positive urine cultures from the time of urodynamics were excluded from analysis. Urine was obtained from the time of urodynamics for uNGAL measurement. Urodynamics were reviewed. High pressure is defined as a detrusor pressure of 40 cm of water or greater at the volume where catheterization is normally performed. Compliance was calculated at the volume where catheterization is performed. RESULTS: A total of 89 patients were included (low pressure, n = 73; high pressure, n = 16 and low compliance, n = 41; normal compliance, n = 40). Median uNGAL concentrations were not different between patients with low and high pressure, but there was a higher median uNGAL concentration in patients with normal compliance compared with those with low compliance. There was no correlation between maximum detrusor pressure and uNGAL concentration, but there was a moderate relationship between compliance and uNGAL concentration (rs = 0.43, p < 0.01 for non-normalized uNGAL and rs = 0.30, p < 0.01 for normalized uNGAL). DISCUSSION AND CONCLUSION: There is an increase in uNGAL concentrations in patients with normal compliance compared with those with low compliance, but no difference between patients with low or high pressure.

An international survey of polypectomy training and assessment.

Background and study aims Colonic polypectomy is acknowledged to be a technically challenging part of colonoscopy. Training in polypectomy is recognized to be often inconsistent. This study aimed to ascertain worldwide practice in polypectomy training. Patients and methods An electronic survey was distributed to endoscopic trainees and trainers in 19 countries asking about their experiences of receiving and delivering training. Participants were also asked about whether formal polypectomy training guidance existed in their country. Results Data were obtained from 610 colonoscopists. Of these responses, 348 (57.0 %) were from trainers and 262 (43.0 %) from trainees; 6.6 % of trainers assessed competency once per year or less often. Just over half (53.1 %) of trainees had ever had their polypectomy technique formally assessed by any trainer. Approximately half the trainees surveyed (51.1 %) stated that the principles of polypectomy had only ever been taught to them intermittently. Of those trainees with the most colonoscopy experience, who had performed over 500 procedures, 48.2 % had had training on removing large polyps of over 10 mm; 46.2 % (121 respondents) of trainees surveyed held no record of the polypectomies they had performed. Only four of the 19 countries surveyed had specific guidelines on polypectomy training. Conclusions A significant number of competent colonoscopists have never been taught how to perform polypectomy. Training guidelines worldwide generally give little direction as to how trainees should acquire polypectomy skills. The learning curve for polypectomy needs to be defined to provide reliable guidance on how to train colonoscopists in this skill.

Modeling emissions from CAFO poultry farms in Poland and evaluating potential risk to surrounding populations.

The world-wide use of concentrated animal feeding operations (CAFOs) for livestock production demands the need to evaluate the potential impact to public health. We estimated the exposure of various airborne pollutants for populations residing in close proximity to 10 poultry CAFOs located in Central Poland. Ammonia (NH3), carbon dioxide (CO2), carbon monoxide (CO), hydrogen sulfide (H2S), methane (CH4), nitrogen dioxide (NO2), nitrous oxide (N2O), sulfur dioxide (SO2), and organic dust were the pollutants of interest for this study. Because no monitoring data were available, we used the steady-state Gaussian dispersion model AERMOD to estimate pollutant concentrations for the exposed population in order to calculate the hazard index (HI) for a combined mixture of chemicals. Our results indicate that while the levels of certain pollutants are expected to exceed background levels commonly found in the environment they did not result in calculated hazard indexes which exceeded unity suggesting low potential for adverse health effects for the surrounding community for the mixture of chemicals. The study was conducted through a cooperation between the Agency for Toxic Substances and Disease Registry (ATSDR) in the USA and the Nofer Institute of Occupational Medicine (NIOM) in Poland.

Windows of Sensitivity to Toxic Chemicals in the Development of Cleft Palates.

Cleft lip and cleft palate are among the most common birth defects worldwide. There is a genetic component to the development of these malformations, as well as evidence that environmental exposures and prescription drug use may exacerbate or even produce these manifestations. Thus, it is important to understand the underlying mechanisms and when these exposures affect development of the growing fetus. The purpose of this investigation was to critically review the available literature related to orofacial cleft formation following chemical exposure and identify specific time frames for windows of sensitivity. Further, an aim was to evaluate the potential for predicting effects in humans based on animal studies. Evidence indicates that chemical causes of cleft palate development are due to dose and timing of exposure, susceptibility of the species (i.e., the genetic makeup), and mechanism of action. Several studies demonstrated that dose is a crucial factor; however, some investigators argued that even more important than dose was timing of exposure. Data show that the window of sensitivity to environmental teratogens in the development of cleft palates is quite narrow and follows closely the window of palatogenesis in the fetus of any given species.

Public health decisions: actions and consequences.

The goal of public health is to promote the best possible health for the whole population. Public health issues are numerous and can be unbelievably complex in form, scope, and possible consequence. Most public health decisions involve assessing several different options, weighing the respective benefits and risks of those options, and making difficult decisions that hopefully provide the greatest benefit to the affected populations. Many risk management decisions involve a variety of societal factors which modify risk assessment choices. The purpose of this paper is to point out difficulties in making decisions that impact public health. The intent of such decisions is to improve public health, but as illustrated in the paper, there can be unintended adverse consequences. Such unplanned issues require continued attention and efforts for responsible officials in the protection of environmental public health. This article presents examples of such events, when in the past, it was necessary to assess and regulate a number of potentially hazardous chemicals commonly used as insecticides, gasoline additives, and wood preservatives.

Inductive measurement of optically hyperpolarized phosphorous donor nuclei in an isotopically enriched silicon-28 crystal.

We experimentally demonstrate the first inductive readout of optically hyperpolarized phosphorus-31 donor nuclear spins in an isotopically enriched silicon-28 crystal. The concentration of phosphorus donors in the crystal was 1.5×10(15) cm(-3), 3 orders of magnitude lower than has previously been detected via direct inductive detection. The signal-to-noise ratio measured in a single free induction decay from a 1 cm(3) sample (≈10(15) spins) was 113. By transferring the sample to an X-band ESR spectrometer, we were able to obtain a lower bound for the nuclear spin polarization at 1.7 K of ∼64%. The (31)P-T2 measured with a Hahn echo sequence was 420 ms at 1.7 K, which was extended to 1.2 s with a Carr Purcell cycle. The T1 of the (31)P nuclear spins at 1.7 K is extremely long and could not be determined, as no decay was observed even on a time scale of 4.5 h. Optical excitation was performed with a 1047 nm laser, which provided above-band-gap excitation of the silicon. The buildup of the hyperpolarization at 4.2 K followed a single exponential with a characteristic time of 577 s, while the buildup at 1.7 K showed biexponential behavior with characteristic time constants of 578 and 5670 s.

Joint toxicity of alkoxyethanol mixtures: contribution of in silico applications.

Exposure to chemicals occurs often as mixtures. Presented in this paper is information on alkoxyethanols and the impact they might have on human health in combination with some commonly found aliphatic and aromatic compounds. Our studies to evaluate the joint toxicity of these chemicals among themselves and in combination with other chemicals reveal a variety of possible outcomes depending on the exposure scenario. The interactions are predominantly based on metabolic pathways and are common among several solvents and organic compounds. Quantitative structure activity relationship (QSAR) analysis can be used with high confidence to identify chemicals that will interact to influence overall joint toxicity. Potential human exposure to a combination of alkoxyethanol, toluene and substituted benzenes may increase reproductive and developmental disease conditions. Inheritable gene alterations result in changes in the enzyme function in different subpopulations causing variations in quantity and/or quality of particular isoenzymes. These changes are responsible for differential metabolism of chemicals in species, genders, and life stages and are often the basis of a population's susceptibility. Unique genotypes introduced as a function of migration can alter the genetic makeup of any given population. Hence special consideration should be given to susceptible populations while conducting chemical health risk assessments.

Quantum information storage for over 180 s using donor spins in a 28Si "semiconductor vacuum".

A quantum computer requires systems that are isolated from their environment, but can be integrated into devices, and whose states can be measured with high accuracy. Nuclear spins in solids promise long coherence lifetimes, but they are difficult to initialize into known states and to detect with high sensitivity. We show how the distinctive optical properties of enriched (28)Si enable the use of hyperfine-resolved optical transitions, as previously applied to great effect for isolated atoms and ions in vacuum. Together with efficient Auger photoionization, these resolved hyperfine transitions permit rapid nuclear hyperpolarization and electrical spin-readout. We combine these techniques to detect nuclear magnetic resonance from dilute (31)P in the purest available sample of (28)Si, at concentrations inaccessible to conventional measurements, measuring a solid-state coherence time of over 180 seconds.

Probe-based confocal laser endomicroscopy compared with standard four-quadrant biopsy for evaluation of neoplasia in Barrett's esophagus.

BACKGROUND AND STUDY AIMS: Surveillance of Barrett's esophagus includes endoscopic inspection with biopsy of suspicious lesions followed by four-quadrant biopsy of the remaining mucosa. We assessed the ability of probe-based confocal laser endomicroscopy (pCLE) to replace biopsy in the endoscopic evaluation of patients with Barrett's esophagus in a prospective and controlled setting. PATIENTS AND METHODS: A total of 68 patients who were referred for endoscopic assessment of Barrett's esophagus were included across three centers. pCLE recordings were interpreted live during the examination as well as in a blinded manner at least 3 months after endoscopy. pCLE diagnosis of neoplasia based on pre-defined criteria was compared with histopathology from suspicious as well as four-quadrant biopsies. RESULTS: A total of 670 pairs of biopsies and pCLE video sequences were available for analysis, with neoplasia (high-grade dysplasia or cancer) being histologically diagnosed in 8.3 %. Specificity and negative predictive value of pCLE in excluding neoplasia was 0.97 (90 %CI 0.95 - 0.98) and 0.93 (0.91 - 0.95) for the blinded evaluation, and 0.95 (0.90 - 0.98) and 0.92 (0.90 - 0.94) for the on-site assessment. Positive predictive values (PPVs) and sensitivity were rather poor for both settings (46 %/28 % [blinded] and 18 %/12 % [on-site], respectively). CONCLUSIONS: pCLE can be regarded as non-inferior to endoscopic biopsy in excluding neoplasia of Barrett's esophagus mucosa. However, due to its low PPV and sensitivity, pCLE may currently not replace standard biopsy techniques for the diagnosis of Barrett's esophagus and associated neoplasia. Further technical development of pCLE and a better understanding of its role in relation to other imaging technologies are necessary.

[Pressure-related dysphonia, recurring pneumonia and supraglottic tumor]. / Belastungsabhängige Dysphonie, rezidivierende Pleuropneumonie und supraglottische Raumforderung.

Urbach-Wiethe syndrome (hyalinosis cutis et mucosae) is an autosomal-recessive inherited disease. It often presents with typical symptoms such as skin lesions (especially in the face and neck area), dyspnea, and maldigestion. Hoarseness is a leading symptom in young children. These manifestations are caused by the assimilation of glycoproteins in mesenchymal tissue. Our case report shows that hoarseness does not necessarily appear only in children, but can also appear later. Furthermore, the assimilation of glycoproteins in the supraglottic area may also cause dysphonia. Due to the varied features of this disease, interdisciplinary check-ups are necessary at regular intervals.

Chemical risk assessment and uncertainty associated with extrapolation across exposure duration.

The Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on priority substances in which available epidemiologic and toxicologic data are reviewed, summarized, and interpreted. When adequate data are available, ATSDR derives health guidance values called minimal risk levels (MRLs) for acute, intermediate, and chronic durations of exposure for oral and inhalation routes of exposure. The MRLs are generally derived by use of the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level/uncertainty factor (LOAEL/UF) approach. The UF usually employed are for LOAEL-to-NOAEL extrapolation, animal to -human extrapolation, and inter-human variability. These health guidance values are intended to serve as screening tools for health assessors and other responders to identify contaminants of concern and potential health effects in the community at hazardous waste sites and during unplanned releases. When guidance values are not available for a specific exposure scenario because of a lack of chronic data, extrapolation across exposure durations may be made. For example, chronic guidance values may be derived from subchronic data by applying an additional uncertainty factor of 10 for extrapolation to chronic exposure duration. In this paper, we analyzed the ratio of chemical-specific LOAELs from acute to intermediate and from intermediate to chronic durations for oral and inhalation exposure routes. In addition, we investigated the impact of chemical structure and chemical structure activity relationship on validation of predictions across exposure durations.

The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract.

BACKGROUND: Confocal laser endomicroscopy (CLE) is rapidly emerging as a valuable tool for gastrointestinal endoscopic imaging. Fluorescent contrast agents are used to optimize imaging with CLE, and intravenous fluorescein is the most widely used contrast agent. Fluorescein is FDA-cleared for diagnostic angiography of the retina. For these indications, the safety profile of fluorescein has been well-documented; however, to date, fluorescein is not cleared for use with CLE. AIMS: To estimate the rate of serious and total adverse events attributable to intravenous fluorescein when used for gastrointestinal CLE. METHODS: We performed a cross sectional survey of 16 International Academic Medical Centres with active research protocols in CLE that involved intravenous fluorescein. Centres using i.v. fluorescein for CLE who were actively monitored for adverse events were included. RESULTS: Sixteen centres performed 2272 gastrointestinal CLE procedures. The most common dose of contrast agent was 2.5-5 mL of 10% sodium fluorescein. No serious adverse events were reported. Mild adverse events occurred in 1.4% of individuals, including nausea/vomiting, transient hypotension without shock, injection site erythema, diffuse rash and mild epigastric pain. The limitation is that only immediate post procedure events were actively monitored. CONCLUSIONS: Use of intravenous fluorescein for gastrointestinal CLE appears to be safe with few acute complications.

Simultaneous subsecond hyperpolarization of the nuclear and electron spins of phosphorus in silicon by optical pumping of exciton transitions.

We demonstrate a method which can hyperpolarize both the electron and nuclear spins of 31P donors in Si at low field, where both would be essentially unpolarized in equilibrium. It is based on the selective ionization of donors in a specific hyperfine state by optically pumping donor bound exciton hyperfine transitions, which can be spectrally resolved in 28Si. Electron and nuclear polarizations of 90% and 76%, respectively, are obtained in less than a second, providing an initialization mechanism for qubits based on these spins, and enabling further ESR and NMR studies on dilute 31P in 28Si.