Observing the onset of pressure-driven K-shell delocalization.

The gravitational pressure in many astrophysical objects exceeds one gigabar (one billion atmospheres)1-3, creating extreme conditions where the distance between nuclei approaches the size of the K shell. This close proximity modifies these tightly bound states and, above a certain pressure, drives them into a delocalized state4. Both processes substantially affect the equation of state and radiation transport and, therefore, the structure and evolution of these objects. Still, our understanding of this transition is far from satisfactory and experimental data are sparse. Here we report on experiments that create and diagnose matter at pressures exceeding three gigabars at the National Ignition Facility5 where 184 laser beams imploded a beryllium shell. Bright X-ray flashes enable precision radiography and X-ray Thomson scattering that reveal both the macroscopic conditions and the microscopic states. The data show clear signs of quantum-degenerate electrons in states reaching 30 times compression, and a temperature of around two million kelvins. At the most extreme conditions, we observe strongly reduced elastic scattering, which mainly originates from K-shell electrons. We attribute this reduction to the onset of delocalization of the remaining K-shell electron. With this interpretation, the ion charge inferred from the scattering data agrees well with ab initio simulations, but it is significantly higher than widely used analytical models predict6.

A statistical method for image-mediated association studies discovers genes and pathways associated with four brain disorders.

Brain imaging and genomics are critical tools enabling characterization of the genetic basis of brain disorders. However, imaging large cohorts is expensive and may be unavailable for legacy datasets used for genome-wide association studies (GWASs). Using an integrated feature selection/aggregation model, we developed an image-mediated association study (IMAS), which utilizes borrowed imaging/genomics data to conduct association mapping in legacy GWAS cohorts. By leveraging the UK Biobank image-derived phenotypes (IDPs), the IMAS discovered genetic bases underlying four neuropsychiatric disorders and verified them by analyzing annotations, pathways, and expression quantitative trait loci (eQTLs). A cerebellar-mediated mechanism was identified to be common to the four disorders. Simulations show that, if the goal is identifying genetic risk, our IMAS is more powerful than a hypothetical protocol in which the imaging results were available in the GWAS dataset. This implies the feasibility of reanalyzing legacy GWAS datasets without conducting additional imaging, yielding cost savings for integrated analysis of genetics and imaging.

Image Translation for Estimating Two-Dimensional Axial Amyloid-Beta PET From Structural MRI.

BACKGROUND: Amyloid-beta and brain atrophy are hallmarks for Alzheimer's Disease that can be targeted with positron emission tomography (PET) and MRI, respectively. MRI is cheaper, less-invasive, and more available than PET. There is a known relationship between amyloid-beta and brain atrophy, meaning PET images could be inferred from MRI. PURPOSE: To build an image translation model using a Conditional Generative Adversarial Network able to synthesize Amyloid-beta PET images from structural MRI. STUDY TYPE: Retrospective. POPULATION: Eight hundred eighty-two adults (348 males/534 females) with different stages of cognitive decline (control, mild cognitive impairment, moderate cognitive impairment, and severe cognitive impairment). Five hundred fifty-two subjects for model training and 331 for testing (80%:20%). FIELD STRENGTH/SEQUENCE: 3 T, T1-weighted structural (T1w). ASSESSMENT: The testing cohort was used to evaluate the performance of the model using the Structural Similarity Index Measure (SSIM) and Peak Signal-to-Noise Ratio (PSNR), comparing the likeness of the overall synthetic PET images created from structural MRI with the overall true PET images. SSIM was computed in the overall image to include the luminance, contrast, and structural similarity components. Experienced observers reviewed the images for quality, performance and tried to determine if they could tell the difference between real and synthetic images. STATISTICAL TESTS: Pixel wise Pearson correlation was significant, and had an R2 greater than 0.96 in example images. From blinded readings, a Pearson Chi-squared test showed that there was no significant difference between the real and synthetic images by the observers (P = 0.68). RESULTS: A high degree of likeness across the evaluation set, which had a mean SSIM = 0.905 and PSNR = 2.685. The two observers were not able to determine the difference between the real and synthetic images, with accuracies of 54% and 46%, respectively. CONCLUSION: Amyloid-beta PET images can be synthesized from structural MRI with a high degree of similarity to the real PET images. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Direct machine learning reconstruction of respiratory variation waveforms from resting state fMRI data in a pediatric population.

In many functional magnetic resonance imaging (fMRI) studies, respiratory signals are unavailable or do not have acceptable quality due to issues with subject compliance, equipment failure or signal error. In large databases, such as the Human Connectome Projects, over half of the respiratory recordings may be unusable. As a result, the direct removal of low frequency respiratory variations from the blood oxygen level-dependent (BOLD) signal time series is not possible. This study proposes a deep learning-based method for reconstruction of respiratory variation (RV) waveforms directly from BOLD fMRI data in pediatric participants (aged 5 to 21 years old), and does not require any respiratory measurement device. To do this, the Lifespan Human Connectome Project in Development (HCP-D) dataset, which includes respiratory measurements, was used to both train a convolutional neural network (CNN) and evaluate its performance. Results show that a CNN can capture informative features from the BOLD signal time course and reconstruct accurate RV timeseries, especially when the subject has a prominent respiratory event. This work advances the use of direct estimation of physiological parameters from fMRI, which will eventually lead to reduced complexity and decrease the burden on participants because they may not be required to wear a respiratory bellows.

MAP2 is differentially phosphorylated in schizophrenia, altering its function.

Schizophrenia (Sz) is a highly polygenic disorder, with common, rare, and structural variants each contributing only a small fraction of overall disease risk. Thus, there is a need to identify downstream points of convergence that can be targeted with therapeutics. Reduction of microtubule-associated protein 2 (MAP2) immunoreactivity (MAP2-IR) is present in individuals with Sz, despite no change in MAP2 protein levels. MAP2 is phosphorylated downstream of multiple receptors and kinases identified as Sz risk genes, altering its immunoreactivity and function. Using an unbiased phosphoproteomics approach, we quantified 18 MAP2 phosphopeptides, 9 of which were significantly altered in Sz subjects. Network analysis grouped MAP2 phosphopeptides into three modules, each with a distinct relationship to dendritic spine loss, synaptic protein levels, and clinical function in Sz subjects. We then investigated the most hyperphosphorylated site in Sz, phosphoserine1782 (pS1782). Computational modeling predicted phosphorylation of S1782 reduces binding of MAP2 to microtubules, which was confirmed experimentally. We generated a transgenic mouse containing a phosphomimetic mutation at S1782 (S1782E) and found reductions in basilar dendritic length and complexity along with reduced spine density. Because only a limited number of MAP2 interacting proteins have been previously identified, we combined co-immunoprecipitation with mass spectrometry to characterize the MAP2 interactome in mouse brain. The MAP2 interactome was enriched for proteins involved in protein translation. These associations were shown to be functional as overexpression of wild type and phosphomimetic MAP2 reduced protein synthesis in vitro. Finally, we found that Sz subjects with low MAP2-IR had reductions in the levels of synaptic proteins relative to nonpsychiatric control (NPC) subjects and to Sz subjects with normal and MAP2-IR, and this same pattern was recapitulated in S1782E mice. These findings suggest a new conceptual framework for Sz-that a large proportion of individuals have a "MAP2opathy"-in which MAP function is altered by phosphorylation, leading to impairments of neuronal structure, synaptic protein synthesis, and function.

MRI of healthy brain aging: A review.

We present a review of the characterization of healthy brain aging using MRI with an emphasis on morphology, lesions, and quantitative MR parameters. A scope review found 6612 articles encompassing the keywords "Brain Aging" and "Magnetic Resonance"; papers involving functional MRI or not involving imaging of healthy human brain aging were discarded, leaving 2246 articles. We first consider some of the biogerontological mechanisms of aging, and the consequences of aging in terms of cognition and onset of disease. Morphological changes with aging are reviewed for the whole brain, cerebral cortex, white matter, subcortical gray matter, and other individual structures. In general, volume and cortical thickness decline with age, beginning in mid-life. Prevalent silent lesions such as white matter hyperintensities, microbleeds, and lacunar infarcts are also observed with increasing frequency. The literature regarding quantitative MR parameter changes includes T1 , T2 , T2 *, magnetic susceptibility, spectroscopy, magnetization transfer, diffusion, and blood flow. We summarize the findings on how each of these parameters varies with aging. Finally, we examine how the aforementioned techniques have been used for age prediction. While relatively large in scope, we present a comprehensive review that should provide the reader with sound understanding of what MRI has been able to tell us about how the healthy brain ages.

Evidence that human and equine erythrocytes could have significant roles in the transport and delivery of amino acids to organs and tissues.

Erythrocytes have a well-defined role in the gaseous exchange of oxygen and carbon dioxide in the mammalian body. The erythrocytes can contain more than half of the free amino acids present in whole blood. Based on measures showing that venous erythrocyte levels of amino acids are much less than arterial erythrocyte levels, it has previously been proposed that erythrocytes also play a role in the delivery of amino acids to tissues in the body. This role has been dismissed because it has been assumed that to act as an amino acid transport vehicle, the erythrocytes should release their entire amino acid content in the capillary beds at the target tissues with kinetic studies showing that this would take too long to achieve. This investigation set out to investigate whether the equine erythrocytes could rapidly take up and release smaller packages of amino acids when exposed to high or low external concentrations of amino acids, because it seemed very unlikely that cells would be able to release all of their amino acids without serious impacts on osmotic balance. Freshly prepared erythrocytes were placed in alternating solutions of high and low amino acid concentrations in PBS to assess the capacities of these cells to rapidly take up and release amino acids depending on the nature of the external environment. It was found that amino acids were rapidly taken up and released in small quantities in each cycle representing 15% of their total load in equine erythrocytes and 16% in human erythrocytes. The capacity for rapid uptake/release of amino acids by equine and human erythrocytes provided evidence to support the theory that mammalian erythrocytes have a significant role in transport of amino acids from the liver to tissues, muscles and organs.

The impact of age and high-risk human papillomavirus (hrHPV) status on the prevalence of high-grade cervical intraepithelial neoplasia (CIN2+) in women with persistent hrHPV-positive, cytology-negative screening samples: a prospective cohort study.

OBJECTIVE: To establish the prevalence of high-grade cervical intraepithelial neoplasia (CIN2+) in women referred to colposcopy with persistent high-risk human papillomavirus (hrHPV) cytology-negative screening sample according to hrHPV genotype, age at referral and colposcopic performance. DESIGN: Prospective cohort study. SETTING: Single colposcopy clinic linked to a population-based screening programme. POPULATION: Women referred with persistent hrHPV cytology-negative routine screening samples. METHODS: Prospective study with descriptive statistics from a single colposcopy unit between June 2014 and July 2019. MAIN OUTCOME MEASURES: Prevalence of hrHPV genotypes and CIN2+, positive predictive value for colposcopic impression, and inadequate colposcopic examinations. RESULTS: A total of 3107 women were referred. Prevalence of CIN2+ was highest for persistent HPV16 infections (10.7%) compared with HPV18 (3.6%) or HPVO (4.7%). Prevalence of CIN2+ declined with age (25-34 years 14.2% to 55-64 years 1.1%) whereas the percentage of women with an inadequate colposcopic examination increased (25-34 years 0.9% to 55-64 years 29.5%). High-grade colposcopic impression fell over time during the study from 16.1 to 5.1%. The positive predictive value for colposcopic impression of CIN2+ was affected by hrHPV genotype (57.3% for HPV16 versus 32.1% for nonHPV16). The adjunctive use of electrical impedance spectroscopy detected an extra 42 cases of CIN2+, which was irrespective of hrHPV genotype. CONCLUSIONS: Primary hrHPV cervical screening increases detection of CIN2+; however, low specificity results in more women being referred to colposcopy with a low prevalence of CIN2+. Colposcopy performs poorly in some groups, particularly with HPVO infections and women over 50 years of age. An appropriate threshold for referral to colposcopy in primary hrHPV screening has not been established. TWEETABLE ABSTRACT: Low prevalence of CIN2+ in HPV-positive negative cytology samples. HPV genotype, age and prevalence of CIN2+ affect colposcopic performance.

Interdatabase Variability in Cortical Thickness Measurements.

The phenomenon of cortical thinning with age has been well established; however, the measured rate of change varies between studies. The source of this variation could be image acquisition techniques including hardware and vendor specific differences. Databases are often consolidated to increase the number of subjects but underlying differences between these datasets could have undesired effects. We explore differences in cerebral cortex thinning between 4 databases, totaling 1382 subjects. We investigate several aspects of these databases, including: 1) differences between databases of cortical thinning rates versus age, 2) correlation of cortical thinning rates between regions for each database, and 3) regression bootstrapping to determine the effect of the number of subjects included. We also examined the effect of different databases on age prediction modeling. Cortical thinning rates were significantly different between databases in all 68 parcellated regions (ANCOVA, P < 0.001). Subtle differences were observed in correlation matrices and bootstrapping convergence. Age prediction modeling using a leave-one-out cross-validation approach showed varying prediction performance (0.64 < R2 < 0.82) between databases. When a database was used to calibrate the model and then applied to another database, prediction performance consistently decreased. We conclude that there are indeed differences in the measured cortical thinning rates between these large-scale databases.

Magnetized Disruption of Inertially Confined Plasma Flows.

The creation and disruption of inertially collimated plasma flows are investigated through experiment, simulation, and analytical modeling. Supersonic plasma jets are generated by laser-irradiated plastic cones and characterized by optical interferometry measurements. Targets are magnetized with a tunable B field with strengths of up to 5 T directed along the axis of jet propagation. These experiments demonstrate a hitherto unobserved phenomenon in the laboratory, the magnetic disruption of inertially confined plasma jets. This occurs due to flux compression on axis during jet formation and can be described using a Lagrangian-cylinder model of plasma evolution implementing finite resistivity. The basic physical mechanisms driving the dynamics of these systems are described by this model and then compared with two-dimensional radiation-magnetohydrodynamic simulations. Experimental, computational, and analytical results discussed herein suggest that contemporary models underestimate the electrical conductivity necessary to drive the amount of flux compression needed to explain observations of jet disruption.

Modelling of protein turnover provides insight for metabolic demands on those specific amino acids utilised at disproportionately faster rates than other amino acids.

The nitrogen balance is regulated by factors such as diet, physical activity, age, pathogenic challenges, and climatic conditions. A paradigm was developed from published recommended rates of protein intake (g/kg/day) with corresponding rates of endogenous protein turnover and excretion, to extrapolate amino acid balances under various conditions. The average proportions of amino acids in the ingested proteins representing a well-balanced diet were used to assess intake and an average human composition profile from five major high-turnover proteins in the body to assess endogenous protein turnover. The amino acid excretion profiles for urine and sweat were constructed for males and females from published data. The model calculated the nitrogen balances for a range of amino acids to determine the amino acid requirements to support daily exertion. Histidine, serine, glycine, and ornithine were in negative balances in males and females and this potential deficit was greater in the higher body-mass ranges. Conversely, leucine, isoleucine, and valine were conserved during nitrogen flux and resulted in positive balances. The model was run under a scenario of high demand for the synthesis of IgG during a response to an infectious challenge which indicated that these were increased requirements for tyrosine, threonine, and valine. It was concluded that these amino acids represent points of limitation to anabolic metabolism by restriction of their supply at critical times of demand. This would especially occur under conditions of fitness training, maintaining intensive exercise regimes, facilitating responses to pathogenic challenge, or recovery from injury.

A qualitative study on the oral health of humanitarian migrants in Canada.

OBJECTIVES: There is limited evidence to guide oral health policy and services for the 25,000 refugees and asylum seekers who arrive in Canada yearly. The purpose of this study was to explore and understand the pre-migration use of dental services, oral health knowledge, and the effects of oral disease among newly arrived humanitarian migrants in order to inform policy and practice for the population. METHODS: Using focused ethnography and the public health model of the dental care process, we conducted face-to-face interviews (50-60 minutes) with a purposive sample of humanitarian migrants who had indicated the need for dental care. We observed mobile dental clinics that provided care to underserved communities in Montreal. Data were analyzed using a thematic and contextual approach that combined inductive and deductive frameworks. RESULTS: Participants included 25 humanitarian migrants from four global geographical regions. Five major thematic categories were explored: problem-based dental consultation, self-assessed oral health status, causes of oral diseases, personal oral hygiene, and good oral health for wellbeing. In their countries of origin, participants consulted a dentist when oral symptoms persisted. They cited excessive sugar consumption and inadequate oral hygiene as causes of oral diseases, and reported significant oral diseases impacts that limited their daily functions and wellbeing once in Canada. CONCLUSIONS: Humanitarian migrants were knowledgeable about causes of oral disease and the importance of good oral health, yet poor oral health continued to affect their lives in Canada in important ways.

Whole head quantitative susceptibility mapping using a least-norm direct dipole inversion method.

A new dipole field inversion method for whole head quantitative susceptibility mapping (QSM) is proposed. Instead of performing background field removal and local field inversion sequentially, the proposed method performs dipole field inversion directly on the total field map in a single step. To aid this under-determined and ill-posed inversion process and obtain robust QSM images, Tikhonov regularization is implemented to seek the local susceptibility solution with the least-norm (LN) using the L-curve criterion. The proposed LN-QSM does not require brain edge erosion, thereby preserving the cerebral cortex in the final images. This should improve its applicability for QSM-based cortical grey matter measurement, functional imaging and venography of full brain. Furthermore, LN-QSM also enables susceptibility mapping of the entire head without the need for brain extraction, which makes QSM reconstruction more automated and less dependent on intermediate pre-processing methods and their associated parameters. It is shown that the proposed LN-QSM method reduced errors in a numerical phantom simulation, improved accuracy in a gadolinium phantom experiment, and suppressed artefacts in nine subjects, as compared to two-step and other single-step QSM methods. Measurements of deep grey matter and skull susceptibilities from LN-QSM are consistent with established reconstruction methods.

Gas-free calibrated fMRI with a correction for vessel-size sensitivity.

Calibrated functional magnetic resonance imaging (fMRI) is a method to independently measure the metabolic and hemodynamic contributions to the blood oxygenation level dependent (BOLD) signal. This technique typically requires the use of a respiratory challenge, such as hypercapnia or hyperoxia, to estimate the calibration constant, M. There has been a recent push to eliminate the gas challenge from the calibration procedure using asymmetric spin echo (ASE) based techniques. This study uses simulations to better understand spin echo (SE) and ASE signals, analytical modelling to characterize the signal evolution, and in vivo imaging to validate the modelling. Using simulations, it is shown how ASE imaging generally underestimates M and how this depends on several parameters of the acquisition, including echo time and ASE offset, as well as the vessel size. This underestimation is the result of imperfect SE refocusing due to diffusion of water through the extravascular environment surrounding the microvasculature. By empirically characterizing this SE attenuation as an exponential decay that increases with echo time, we have proposed a quadratic ASE biophysical signal model. This model allows for the characterization and compensation of the SE attenuation if SE and ASE signals are acquired at multiple echo times. This was tested in healthy subjects and was found to significantly increase the estimates of M across grey matter. These findings show promise for improved gas-free calibration and can be extended to other relaxation-based imaging studies of brain physiology.

Modeling hyperoxia-induced BOLD signal dynamics to estimate cerebral blood flow, volume and mean transit time.

A new method is proposed for obtaining cerebral perfusion measurements whereby blood oxygen level dependent (BOLD) MRI is used to dynamically monitor hyperoxia-induced changes in the concentration of deoxygenated hemoglobin in the cerebral vasculature. The data is processed using kinetic modeling to yield perfusion metrics, namely: cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Ten healthy human subjects were continuously imaged with BOLD sequence while a hyperoxic (70% O2) state was interspersed with baseline periods of normoxia. The BOLD time courses were fit with exponential uptake and decay curves and a biophysical model of the BOLD signal was used to estimate oxygen concentration functions. The arterial input function was derived from end-tidal oxygen measurements, and a deconvolution operation between the tissue and arterial concentration functions was used to yield CBF. The venous component of the CBV was calculated from the ratio of the integrals of the estimated tissue and arterial concentration functions. Mean gray and white matter measurements were found to be: 61.6 ±â€¯13.7 and 24.9 ±â€¯4.0 ml 100 g-1 min-1 for CBF; 1.83 ±â€¯0.32 and 1.10 ±â€¯0.19 ml 100 g-1 for venous CBV; and 2.94 ±â€¯0.52 and 3.73 ±â€¯0.60 s for MTT, respectively. We conclude that it is possible to derive CBF, CBV and MTT metrics within expected physiological ranges via analysis of dynamic BOLD fMRI acquired during a period of hyperoxia.

Liquid Structure of Shock-Compressed Hydrocarbons at Megabar Pressures.

We present results for the ionic structure in hydrocarbons (polystyrene, polyethylene) that were shock compressed to pressures of up to 190 GPa, inducing rapid melting of the samples. The structure of the resulting liquid is then probed using in situ diffraction by an x-ray free electron laser beam, demonstrating the capability to obtain reliable diffraction data in a single shot, even for low-Z samples without long range order. The data agree well with ab initio simulations, validating the ability of such approaches to model mixed samples in states where complex interparticle bonds remain, and showing that simpler models are not necessarily valid. While the results clearly exclude the possibility of complete carbon-hydrogen demixing at the conditions probed, they also, in contrast to previous predictions, indicate that diffraction is not always a sufficient diagnostic for this phenomenon.

Absolute Equation-of-State Measurement for Polystyrene from 25 to 60 Mbar Using a Spherically Converging Shock Wave.

We have developed an experimental platform for the National Ignition Facility that uses spherically converging shock waves for absolute equation-of-state (EOS) measurements along the principal Hugoniot. In this Letter, we present one indirect-drive implosion experiment with a polystyrene sample that employs radiographic compression measurements over a range of shock pressures reaching up to 60 Mbar (6 TPa). This significantly exceeds previously published results obtained on the Nova laser [R. Cauble et al., Phys. Rev. Lett. 80, 1248 (1998)PRLTAO0031-900710.1103/PhysRevLett.80.1248] at a strongly improved precision, allowing us to discriminate between different EOS models. We find excellent agreement with Kohn-Sham density-functional-theory-based molecular dynamics simulations.

Atomic versus molecular Auger decay in CH2Cl2 and CD2Cl2 molecules.

Autoionization spectra of CH2Cl2 and CD2Cl2 molecules after Cl 2p excitation are studied. The two molecular and atomic Auger transitions are examined and assigned. The contribution of atomic Auger transitions is lower in the deuterated molecule. In addition, to support the presence of the ultrafast dissociation mechanism in the dichloromethane molecule, a series of high-level ab initio quantum mechanical calculations were performed at multiconfigurational self-consistent field (MCSCF) and multireference configuration interaction (MRCI) levels of theory. Minimum energy pathways for the dissociation of the dichloromethane molecule have been calculated by taking into account the spin-orbit splitting between the singlet and triplet transitions in the Cl 2p edge.

Orbit period modulation for relative motion using continuous low thrust in the two-body and restricted three-body problems.

This paper presents rich new families of relative orbits for spacecraft formation flight generated through the application of continuous thrust with only minimal intervention into the dynamics of the problem. Such simplicity facilitates implementation for small, low-cost spacecraft with only position state feedback, and yet permits interesting and novel relative orbits in both two- and three-body systems with potential future applications in space-based interferometry, hyperspectral sensing, and on-orbit inspection. Position feedback is used to modify the natural frequencies of the linearised relative dynamics through direct manipulation of the system eigenvalues, producing new families of stable relative orbits. Specifically, in the Hill-Clohessy-Wiltshire frame, simple adaptations of the linearised dynamics are used to produce a circular relative orbit, frequency-modulated out-of-plane motion, and a novel doubly periodic cylindrical relative trajectory for the purposes of on-orbit inspection. Within the circular restricted three-body problem, a similar minimal approach with position feedback is used to generate new families of stable, frequency-modulated relative orbits in the vicinity of a Lagrange point, culminating in the derivation of the gain requirements for synchronisation of the in-plane and out-of-plane frequencies to yield a singly periodic tilted elliptical relative orbit with potential use as a Lunar far-side communications relay. The Δ v requirements for the cylindrical relative orbit and singly periodic Lagrange point orbit are analysed, and it is shown that these requirements are modest and feasible for existing low-thrust propulsion technology.

Prevalence of high-grade cervical intraepithelial neoplasia in women with persistent high-risk HPV genotypes and negative cytology.

INTRODUCTION: Primary HPV screening will be implemented into the English Cervical Screening Programme by 2019. Its impact upon women referred to colposcopy, with negative cytology but persistently positive high-risk HPV (hrHPV), remains unreported from UK Sentinel sites. HPV primary screening was introduced in Sheffield, UK in April 2013; this paper reports its impact on the service. METHODS: A retrospective cohort study was performed from June 2014 to July 2016 at the Jessop Wing Colposcopy Unit, Sheffield. UK. Data were obtained from the pathology and colposcopy databases and cross-referenced with case-notes and pathology results for women referred with persistently positive hrHPV, cytology negative samples. Patient demographics, hrHPV genotype, biopsy rates, histological diagnoses, management, and outcomes were collected and baseline statistics performed. RESULTS: During the study 1076 women were seen. Most frequent hrHPV genotypes were: hrHPV other, 41%; and HPV16, 33%. The majority (72%) were found to have normal colposcopy; 28% had an abnormal colposcopic assessment (11% low-grade; 11% high-grade; 6% inadequate). The majority were discharged (83%) and only 5% underwent LLETZ. No cancers were detected. High-grade cervical intraepithelial neoplasia (CIN) was found in 7%; overall risk of CIN2 was 1/29; 1/30 for CIN3. Presence of HPV16 was associated with a significantly higher risk of high-grade CIN; 1/9. CONCLUSION: This is the first study to report results for women referred to colposcopy with cytology negative, persistently positive hrHPV. Disease prevalence is low, although women with HPV16 have a significantly higher likelihood of high-grade disease compared to other HPV subtypes.