A Common Infection in a Highly Atypical Patient: Hematochezia From a Cytomegalovirus Colonic Ulcer in a Young and Healthy Immunocompetent Patient.

Gastrointestinal (GI) cytomegalovirus (CMV) infections are far more common in immunocompromised as opposed to immunocompetent patients. Immunocompetent patients who develop GI tract CMV infections are typically older with medical comorbidities. As such, descriptions of GI CMV infections in younger immunocompetent patients are lacking. Here, we present a case of a GI CMV infection in a young and healthy immunocompetent patient. A 41-year-old male with hyperlipidemia and hypothyroidism presented with painless, intermittent hematochezia. He denied changes in bowel habits or appetite, abdominal pain, fevers, chills, fatigue, or weight loss. His history was pertinent for insertive and receptive intercourse with one male partner. Medications were emtricitabine/tenofovir for pre-exposure prophylaxis, levothyroxine, and atorvastatin. A colonoscopy revealed a cecal ulcer surrounded by nodular-appearing mucosa that felt firm and friable when biopsied. The remaining colon and terminal ileum were normal. There was no diverticulosis or hemorrhoids. Pathology was positive for CMV. A subsequent serological evaluation revealed a normal complete blood count and comprehensive metabolic panel. Tests for human immunodeficiency virus, syphilis, viral hepatitis, chlamydia, and gonorrhea were negative. He was treated with valganciclovir 900 mg twice daily for 21 days. A subsequent test for CMV deoxyribonucleic acid polymerase chain was negative. Hematochezia resolved. A repeat colonoscopy revealed normal mucosa in the cecum. GI CMV infections in immunocompetent patients are rare and typically occur in older patients with medical comorbidities. Further, such case reports are needed to inform clinicians about risk factors and the presentation of GI CMV infections in young healthy immunocompetent patients.

Dysregulation of Copper Metabolism in a Patient With Acute-on-Chronic Liver Failure Worked up for Fulminant Wilson Disease.

Wilson disease (WD) is estimated present in 6%-12% of patients younger than 40 years hospitalized with acute liver failure (ALF). Fulminant WD carries a poor prognosis without treatment. A 36-year-old man with HIV, chronic hepatitis B virus, and alcohol use had ceruloplasmin 6.4 mg/dL and 24-hour urine copper 180 µg/L. WD workup was otherwise negative, including ophthalmic examination, hepatic copper quantification, ATP7B sequencing, and brain MRI. ALF commonly features copper dysregulation. Few studies on WD biomarkers have included fulminant WD. Our patient with WD biomarkers and other causes of liver failure highlights the need to study copper dysregulation in ALF.

Quantifying the direct cost benefits of vestibular telemetry using the CAVA system to diagnose the causes of dizziness.

BACKGROUND: It can be challenging to diagnose the cause of a patient's dizziness. Patients face significant delays before receiving a correct diagnosis as they will undergo many diagnostic tests under several different medical specialities. As well as prolonging the suffering of patients, these problems place a significant financial burden on health services worldwide. We have developed a wearable medical device which has the potential to diagnose the cause of a patient's dizziness using vestibular telemetry captured over a thirty-day period. We sought to quantify the potential direct cost savings of an alternative diagnostic pathway using our diagnostic device. METHODS: In this work, we identified the existing diagnostic pathways followed by patients reporting dizziness to their General Practitioner, and modelled the best and worst-case direct costs of providing a patient with a correct diagnosis. We estimated the potential cost of our alternative pathway, and calculated the cost savings this could provide to the NHS. RESULTS: The results show that our alternative diagnostic pathway could reduce the time and direct cost associated with providing a correct diagnosis. We present a potential indicative cost-saving of between £631 and £1305, per patient. CONCLUSION: Our alternative diagnostic pathway would reduce the time taken to correctly diagnose patients with vertigo. This in turn would facilitate faster access to targeted treatments, reduce unnecessary interventions, and reduce the suffering of patients. These improvements would also lead to other savings, such as reducing the amount of sick leave taken by patients to attend appointments, and freeing up of NHS time to see other patients.

Reconstructing animated eye movements from electrooculography data to aid the diagnosis of vestibular disorders.

OBJECTIVE: To develop a method of visualising electrooculography data to improve the interpretability of nystagmus eye-movements captured using the Continuous Ambulatory Vestibular Assessment (CAVA®) device. DESIGN: We are currently undertaking a clinical investigation to evaluate the capabilities of the CAVA® device to detect periods of pathological nystagmus. The work presented here was undertaken using unblinded data obtained from the preliminary phase of this investigation. STUDY SAMPLE: One patient with Ménière's disease and one with Benign Paroxysmal Positional Vertigo. RESULTS: Using the electrooculography data captured by the CAVA® device, we reconstructed 2D animations of patients' eye movements during attacks of vertigo. We were able to reanimate nystagmus produced as a consequence of two conditions. Concurrent video footage showed that the animations were visually very similar to the patient's actual eye-movements, excepting torsional eye-movements. CONCLUSIONS: The reconstructed animations provide an alternative presentation modality, enabling clinicians to largely interpret electrooculography data as if they were present during a vertigo attack. We were able to recreate nystagmus from attacks experienced in the community rather than a clinical setting. This information provides an objective record of a patient's nystagmus and could be used to complement a full neurotologic history when considering diagnosis and treatment options.

Detecting positional vertigo using an ensemble of 2D convolutional neural networks.

The aim of the work presented here was to develop a system that can automatically identify attacks of dizziness occurring in patients suffering from positional vertigo, which occurs when sufferers move their head into certain positions. We used our novel medical device, CAVA, to record eye- and head-movement data continually for up to 30 days in patients diagnosed with a disorder called Benign Paroxysmal Positional Vertigo. Building upon our previous work, we describe a novel ensemble of five 2D Convolutional Neural Networks, using composite recognition features, including eye-movement data and three-channel accelerometer data. We achieve an F 1 score of 0.63 across an 11-fold cross-fold validation experiment, demonstrating that the system can detect a few seconds of motion provoked dizziness from within over a 100 h of normal eye-movement data. We show that the system outperforms our previous 1D Neural Network approach, and that our ensemble classifier is superior to each of the individual networks it contains. We also demonstrate that our composite recognition features provide improved performance over results obtained using the individual data sources independently.

Clinical Techniques and Technology: Vestibular Telemetry.

When a patient presents to a clinician with dizziness, it can be difficult for the patient to describe their symptoms in a clear manner, and clinical examination often yields entirely normal results. Ideally, it would be favorable to measure key physiological parameters during their episodes of dizziness. From a clinical perspective, this would allow a more timely and more accurate diagnosis. From a research perspective, it would allow a greater understanding of how the vestibular system malfunctions as a consequence of vestibular disease. The authors of this report have been funded by the UK Medical Research Council to develop and test a novel technology to measure, record, and analyze key physiological parameters provided by the dizzy individual during an episode of dizziness while active in the community. We provide the context to evolving work in this field, the outcome of preliminary studies, and a consideration of future opportunities.

Towards Providing an Automated Approach to Differentiating the Nystagmus of Ménière's Disease, Vestibular Migraine, and Benign Paroxysmal Positional Vertigo.

OBJECTIVE: The diagnosis of vertigo is challenging, particularly as patients usually present while asymptomatic. We have developed an ambulatory medical device that allows vestibular telemetry to record eye movements over a 30-day period to aid the diagnosis of vertigo. We have undertaken proof-of-concept work to identify unique properties of nystagmus that could be used to differentiate between three of the most common causes of vertigo: Ménière's disease, vestibular migraine, and Benign Paroxysmal Positional Vertigo. PATIENTS: We analyze the nystagmus from patients with a diagnosis of Ménière's disease, vestibular migraine, and Benign Paroxysmal Positional Vertigo. INTERVENTIONS: Our vestibular telemetry system includes a wearable, ambulatory monitor which continuously records horizontal and vertical eye-movements, as well as three-axis movements of the head. MAIN OUTCOME MEASURES: Horizontal and vertical eye-movement data, and three-axis head positioning data. RESULTS: Sixteen participants were enrolled onto the study and three reported experiencing rotatory vertigo during their 30-day trial, confirmed by the presence of nystagmus in their eye-movement traces. Vestibular telemetry revealed distinct differences between the nystagmus produced during an acute Ménière's attack, and attacks of vestibular migraine and Benign Paroxysmal Positional Vertigo. Attack frequency, nystagmus duration, whether the nystagmus onset was motion provoked, nystagmus direction, slow phase velocity, and slow phase duration were found to be discriminatory features that could be exploited to allow an automated diagnosis to be made. CONCLUSIONS: The data provided by vestibular telemetry can be used to differentiate between different inner-ear causes of dizziness.

1D Convolutional Neural Networks for Detecting Nystagmus.

Vertigo is a type of dizziness characterised by the subjective feeling of movement despite being stationary. One in four individuals in the community experience symptoms of dizziness at any given time, and it can be challenging for clinicians to diagnose the underlying cause. When dizziness is the result of a malfunction in the inner-ear, the eyes flicker and this is called nystagmus. In this article we describe the first use of Deep Neural Network architectures applied to detecting nystagmus. The data used in these experiments was gathered during a clinical investigation of a novel medical device for recording head and eye movements. We describe methods for training networks using very limited amounts of training data, with an average of 11 mins of nystagmus across four subjects, and less than 24 hours of data in total, per subject. Our methods work by replicating and modifying existing samples to generate new data. In a cross-fold validation experiment, we achieve an average F1 score of 0.59 (SD = 0.24) across all four folds, showing that the methods employed are capable of identifying periods of nystagmus with a modest degree of accuracy. Notably, we were also able to identify periods of pathological nystagmus produced by a patient during an acute attack of Ménière's Disease, despite training the network on nystagmus that was induced by different means.

Nystagmus during an acute Ménière's attack: from prodrome to recovery.

OBJECTIVE: We are currently undertaking a clinical investigation to evaluate the diagnostic capability of a system for detecting periods of pathological dizziness. This article presents an analysis of the data captured during an acute attack of Ménière's disease. DESIGN: The Continuous Ambulatory Vestibular Assessment (CAVA) device is worn by patients in the community, and continuously records eye and head movement data (vestibular telemetry). STUDY SAMPLE: A 53-year-old lady with a fifteen-year history of left-sided unilateral Ménière's disease. RESULTS: The patient wore the device nearly continuously for thirty days. The data revealed a three-hour long attack of vertigo consisting of four separate phases of nystagmus. The duration, beat-direction and slow phase velocity of the nystagmus evolved through time. The first phase contained isolated nystagmus beats which preceded the patient's record of the vertigo attack onset but coincided with anticipation of an impending vertigo attack. CONCLUSIONS: CAVA provides a unique insight into the physiological parameters present during episodes of dizziness. Here, it has provided the first full example of an acute Ménière's attack, including a period of prodrome. These findings have implications for the prediction of vertigo attack onset, for the diagnosis of Ménière's disease and other diseases resulting in dizziness.

Automatic nystagmus detection and quantification in long-term continuous eye-movement data.

Symptoms of dizziness or imbalance are frequently reported by people over 65. Dizziness is usually episodic and can have many causes, making diagnosis problematic. When it is due to inner-ear malfunctions, it is usually accompanied by abnormal eye-movements called nystagmus. The CAVA (Continuous Ambulatory Vestibular Assessment) device has been developed to provide continuous monitoring of eye-movements to gain insight into the physiological parameters present during a dizziness attack. In this paper, we describe novel algorithms for detecting short periods of artificially induced nystagmus from the long-term eye movement data collected by the CAVA device. In a blinded trial involving 17 healthy subjects, each participant induced nystagmus artificially on up to eight occasions by watching a short video on a VR headset. Our algorithms detected these short periods with an accuracy of 98.77%. Additionally, data relating to vestibular induced nystagmus was collected, analysed and then compared to a conventional technique for assessing nystagmus during caloric testing. The results show that a range of nystagmus can be identified and quantified using computational methods applied to long-term eye-movement data captured by the CAVA device.

Shaping of a three-dimensional carnivorous trap through modulation of a planar growth mechanism.

Leaves display a remarkable range of forms, from flat sheets with simple outlines to cup-shaped traps. Although much progress has been made in understanding the mechanisms of planar leaf development, it is unclear whether similar or distinctive mechanisms underlie shape transformations during development of more complex curved forms. Here, we use 3D imaging and cellular and clonal analysis, combined with computational modelling, to analyse the development of cup-shaped traps of the carnivorous plant Utricularia gibba. We show that the transformation from a near-spherical form at early developmental stages to an oblate spheroid with a straightened ventral midline in the mature form can be accounted for by spatial variations in rates and orientations of growth. Different hypotheses regarding spatiotemporal control predict distinct patterns of cell shape and size, which were tested experimentally by quantifying cellular and clonal anisotropy. We propose that orientations of growth are specified by a proximodistal polarity field, similar to that hypothesised to account for Arabidopsis leaf development, except that in Utricularia, the field propagates through a highly curved tissue sheet. Independent evidence for the polarity field is provided by the orientation of glandular hairs on the inner surface of the trap. Taken together, our results show that morphogenesis of complex 3D leaf shapes can be accounted for by similar mechanisms to those for planar leaves, suggesting that simple modulations of a common growth framework underlie the shaping of a diverse range of morphologies.

An investigation into the diagnostic accuracy, reliability, acceptability and safety of a novel device for Continuous Ambulatory Vestibular Assessment (CAVA).

Dizziness is a common condition that is responsible for a significant degree of material morbidity and burden on health services. It is usually episodic and short-lived, so when a patient presents to their clinician, examination is normal. The CAVA (Continuous Ambulatory Vestibular Assessment) device has been developed to provide continuous monitoring of eye-movements, allowing insight into the physiological parameters present during a dizziness attack. This article describes the first clinical investigation into the medical and technical aspects of this new diagnostic system. Seventeen healthy subjects wore the device near continuously for up to thirty days, artificially inducing nystagmus on eight occasions. 405 days' worth of data was captured, comprising around four billion data points. A computer algorithm developed to detect nystagmus demonstrated a sensitivity of 99.1% (95% CI: 95.13% to 99.98%) and a specificity of 98.6% (95% CI: 96.54% to 99.63%). Eighty-two percent of participants wore the device for a minimum of eighty percent of each day. Adverse events were self-limiting and mostly the consequence of skin stripping from the daily replacement of the electrodes. The device was shown to operate effectively as an ambulatory monitor, allowing the reliable detection of artificially induced nystagmus.

Ectopic BASL Reveals Tissue Cell Polarity throughout Leaf Development in Arabidopsis thaliana.

Tissue-wide polarity fields, in which cell polarity is coordinated across the tissue, have been described for planar organs such as the Drosophila wing and are considered important for coordinating growth and differentiation [1]. In planar plant organs, such as leaves, polarity fields have been identified for subgroups of cells, such as stomatal lineages [2], trichomes [3, 4], serrations [5], or early developmental stages [6]. Here, we show that ectopic induction of the stomatal protein BASL (BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE) reveals a tissue-wide epidermal polarity field in leaves throughout development. Ectopic GFP-BASL is typically localized toward the proximal end of cells and to one lobe of mature pavement cells, revealing a polarity field that aligns with the proximodistal axis of the leaf (base to tip). The polarity field is largely parallel to the midline of the leaf but diverges in more lateral positions, particularly at later stages in development, suggesting it may be deformed during growth. The polarity field is observed in the speechless mutant, showing that it is independent of stomatal lineages, and is observed in isotropic cells, showing that cell shape anisotropy is not required for orienting polarity. Ectopic BASL forms convergence and divergence points at serrations, mirroring epidermal PIN polarity patterns, suggesting a common underlying polarity mechanism. Thus, we show that similar to the situation in animals, planar plant organs have a tissue-wide cell polarity field, and this may provide a general cellular mechanism for guiding growth and differentiation.

Macro optical projection tomography for large scale 3D imaging of plant structures and gene activity.

Optical projection tomography (OPT) is a well-established method for visualising gene activity in plants and animals. However, a limitation of conventional OPT is that the specimen upper size limit precludes its application to larger structures. To address this problem we constructed a macro version called Macro OPT (M-OPT). We apply M-OPT to 3D live imaging of gene activity in growing whole plants and to visualise structural morphology in large optically cleared plant and insect specimens up to 60 mm tall and 45 mm deep. We also show how M-OPT can be used to image gene expression domains in 3D within fixed tissue and to visualise gene activity in 3D in clones of growing young whole Arabidopsis plants. A further application of M-OPT is to visualise plant-insect interactions. Thus M-OPT provides an effective 3D imaging platform that allows the study of gene activity, internal plant structures and plant-insect interactions at a macroscopic scale.

2-(2-Methyl-benzo-yl)benzoic acid: catemeric hydrogen bonding in a γ-keto acid.

The crystal structure of the title compound, C15H12O3, displays catemeric aggregation involving O-H⋯O hydrogen bonds progressing from the carboxyl group of one mol-ecule to the ketone O atom of another glide-related neighbor. The mol-ecule is twisted, with the toluene 80.61 (3)° out of plane with respect to the phenyl group of the benzoic acid. The acid group makes a dihedral angle of 13.79 (14)° with the attached phenyl ring. The mol-ecules are achiral, but the space group glide planes create alternating conformational chirality in the chain units. The four hydrogen-bonding chains progress along [001] in an A-A-B-B pattern (right-to-left versus left-to-right), and are related to each other by the center of symmetry at (0.5, 0.5, 0.5) in the chosen cell. There is one close contact (2.54 Å) between a phenyl H atom and the acid carbonyl from a symmetry-related mol-ecule.

3-Acetyl-benzoic acid.

In the crystal structure of the title compound, C(9)H(8)O(3), essentially planar mol-ecules [the carboxyl group makes a dihedral angle of 4.53 (7)° with the plane of the ring, while the acid group forms a dihedral angle of 3.45 (8)° to the ring] aggregate by centrosymmetric hydrogen-bond pairing of ordered carboxyl groups. This yields dimers which have two orientations in a unit cell, creating a herringbone pattern. In addition, two close C-H⋯O inter-molecular contacts exist: one is between a methyl H atom and the ketone of a symmetry-related mol-ecule and the other involves a benzene H atom and the carboxyl group O atom of another mol-ecule. The crystal studied was a non-merohedral twin with twin law [100, 00, 0] and a domain ratio of 0.8104(14): 0.1896(14).

Improvements in complex mixture analysis by NMR: DQF-COSY iDOSY.

Diffusion-ordered NMR spectroscopy (DOSY NMR) is a highly useful tool for the study of complex mixtures via NMR. Often, spectral overlap limits the ability of obtaining cleanly separated subspectra of the components due to inherently instable multiexponential fits or data inversion procedures. Three-dimensional DOSY variants offer the advantage of separating individual peaks in an additional dimension, such that robust monoexponential fits to cross-peaks may be used to determine the diffusion coefficients with higher accuracy. For sensitivity reasons, methods based on proton nuclei are preferable. We show that a double-quantum-filtered COSY-DOSY experiment provides advantages over COSY-DOSY, while high signal-to-noise ratios are maintained. We demonstrate the viability of the technique by applying it to a solution of single-stranded DNA oligomers and to a mixture of unprocessed beeswax and decanol.

trans-4-Acetylcyclohexanecarboxylic acid and (+/-)-trans-2-acetylcyclohexanecarboxylic acid: hydrogen-bonding patterns in two isomeric keto acids.

Both title compounds, C(9)H(14)O(3), display carboxyl-dimer hydrogen-bonding patterns. The 4-acetyl isomer adopts a chiral conformation with negligible disordering of the methyl and carboxyl groups and forms centrosymmetric dimers across the b and c edges of the chosen cell [O.O = 2.667 (3) A and O-H.O = 175 degrees ]. Intermolecular C-H.O close contacts were found for both carbonyl groups. In the 2-acetyl isomer, there is no intramolecular interaction between the carboxyl and acetyl groups and the hydrogen bonding involves centrosymmetric carboxyl dimerization across the ab and ac faces of the chosen cell [O.O = 2.668 (2) A and O-H.O = 173 degrees ]. The carboxyl group is negligibly disordered, but significant rotational disordering was found for the acetyl methyl group. An intermolecular C-H.O close contact was found involving the ketone group.

(+)-3,11-Dioxoandrost-4-ene-17 beta-carboxylic acid: catemeric hydrogen bonding in a steroidal keto acid.

The title keto acid, C(20)H(26)O(4), forms carboxyl-to-ketone hydrogen-bonding catemers [O...O = 2.653 (5) A and O[bond]H...O = 172 (5) degrees ], linking translationally related molecules via the A-ring ketone. The two molecules in the cell form two parallel counter-directional chains, screw-related in b. A total of four intermolecular C[bond]H...O[double bond]C close contacts was found, involving both ketone functions.

1'-Acetylferrocene-1-carboxylic acid: an instance of hydrogen bonding in the rare dimeric acid-to-ketone mode.

The title compound, [Fe(C(6)H(5)O(2))(C(7)H(7)O)], adopts a conformation involving partial staggering of its rings and aggregates in the solid as acid-to-ketone hydrogen-bonding dimers [O.O = 2.720(4)A and O-H...O = 164 degree] having centrosymmetrically related components. Close intermolecular C-H...O contacts were found to both carboxyl O atoms.