Respiratory virus infections in decedents in a large, urban medical examiner's office.

OBJECTIVE: Most respiratory virus surveillance relies on medically attended respiratory illness, but an understanding of the true patterns of infection independent of care-seeking behaviour would enhance clinical and public health responses to respiratory virus outbreaks. We evaluated the potential of decedent surveillance by estimating the burden of respiratory virus infection in decedents in a large, urban medical examiner's office. STUDY DESIGN: Observational. METHODS: In 2020-2022, we tested nasopharyngeal swabs from 4121 decedents in Detroit, Michigan for 15 respiratory viruses, including SARS-CoV-2, respiratory syncytial virus, and influenza virus A and B. We analysed infection prevalence over time and by age, sex, race/ethnicity, and manner of death. RESULTS: Of 4113 valid tests, 30.2% were positive for at least one virus, and 6.1% were positive for multiple viruses. All viruses were detected except for influenza A/H1N1 and influenza B. The most prevalent viruses were SARS-CoV-2 (15.7%), rhinovirus (11.2%), and adenovirus (4.9%), which were detected in all months. Most viruses exhibited decreasing prevalence with age, higher prevalence among Black and Hispanic than among White decedents and lower prevalence among deaths from natural causes; SARS-CoV-2 was a notable exception to the patterns by age and manner of death, instead reflecting community trends in catchment counties. CONCLUSIONS: There was high prevalence and diversity of respiratory viruses in decedents entering a large, urban medical examiner's office. Decedent surveillance could offer a clearer picture of the true underlying burden of infection, motivating public health priorities for intervention and vaccine development, and augmenting data for real-time response to respiratory virus outbreaks.

Exploring the use of Granger causality for the identification of chemical exposure based on physiological data.

Wearable sensors offer new opportunities for the early detection and identification of toxic chemicals in situations where medical evaluation is not immediately possible. We previously found that continuously recorded physiology in guinea pigs can be used for early detection of exposure to an opioid (fentanyl) or a nerve agent (VX), as well as for differentiating between the two. Here, we investigated how exposure to these different chemicals affects the interactions between ECG and respiration parameters as determined by Granger causality (GC). Features reflecting such interactions may provide additional information and improve models differentiating between chemical agents. Traditional respiration and ECG features, as well as GC features, were extracted from data of 120 guinea pigs exposed to VX (n = 61) or fentanyl (n = 59). Data were divided in a training set (n = 99) and a test set (n = 21). Minimum Redundancy Maximum Relevance (mRMR) and Support Vector Machine (SVM) algorithms were used to, respectively, perform feature selection and train a model to discriminate between the two chemicals. We found that ECG and respiration parameters are Granger-related under healthy conditions, and that exposure to fentanyl and VX affected these relationships in different ways. SVM models discriminated between chemicals with accuracy of 95% or higher on the test set. GC features did not improve the classification compared to traditional features. Respiration features (i.e., peak inspiratory and expiratory flow) were the most important to discriminate between different chemical's exposure. Our results indicate that it may be feasible to discriminate between chemical exposure when using traditional physiological respiration features from wearable sensors. Future research will examine whether GC features can contribute to robust detection and differentiation between chemicals when considering other factors, such as generalizing results across species.

Using supramolecular machinery to engineer directional charge propagation in photoelectrochemical devices.

Molecular photoelectrochemical devices are hampered by electron-hole recombination after photoinduced electron transfer, causing losses in power conversion efficiency. Inspired by natural photosynthesis, we demonstrate the use of supramolecular machinery as a strategy to inhibit recombination through an organization of molecular components that enables unbinding of the final electron acceptor upon reduction. We show that preorganization of a macrocyclic electron acceptor to a dye yields a pseudorotaxane that undergoes a fast (completed within ~50 ps) 'ring-launching' event upon electron transfer from the dye to the macrocycle, releasing the anionic macrocycle and thus reducing charge recombination. Implementing this system into p-type dye-sensitized solar cells yielded a 16-fold and 5-fold increase in power conversion efficiency compared to devices based on the two control dyes that are unable to facilitate pseudorotaxane formation. The active repulsion of the anionic macrocycle with concomitant reformation of a neutral pseudorotaxane complex circumvents recombination at both the semiconductor-electrolyte and semiconductor-dye interfaces, enabling a threefold enhancement in hole lifetime.

Extreme ultraviolet-excited time-resolved luminescence spectroscopy using an ultrafast table-top high-harmonic generation source.

We present a table-top extreme ultraviolet (XUV) beamline for measuring time- and frequency-resolved XUV-excited optical luminescence (XEOL) with additional femtosecond-resolution XUV transient absorption spectroscopy functionality. XUV pulses are generated via high-harmonic generation using a near-infrared pulse in a noble gas medium and focused to excite luminescence from a solid sample. The luminescence is collimated and guided into a streak camera where its spectral components are temporally resolved with picosecond temporal resolution. We time-resolve XUV-excited luminescence and compare the results to luminescence decays excited at longer wavelengths for three different materials: (i) sodium salicylate, an often used XUV scintillator; (ii) fluorescent labeling molecule 4-carbazole benzoic (CB) acid; and (iii) a zirconium metal oxo-cluster labeled with CB, which is a photoresist candidate for extreme-ultraviolet lithography. Our results establish time-resolved XEOL as a new technique to measure transient XUV-driven phenomena in solid-state samples and identify decay mechanisms of molecules following XUV and soft-x-ray excitation.

The role of national and international veterinary laboratories.

In the field of diagnostic test validation, World Organisation for Animal Health (OIE) Reference Laboratories (RLs) have a pivotal role and provide the international community with impartial advice and support in the selection, development and validation of diagnostic tests, which can be applied to the specialist diseases for which they are designated. National RLs provide an invaluable function in supporting the introduction, ongoing validation and application of validated diagnostic tests in line with international standards. Experienced staff with extensive knowledge of such systems and access to specialist facilities for conducting work are available to monitor changes or advancements in technology. They consider their relevance and value to evolving diagnostic test requirements. Reference Laboratories often have a broad mandate of activity linking research or development programmes and surveillance activities to benefit the continual assessment and, if necessary, improvement of diagnostic tools. Reference Laboratories maintain or have access to unique biological archives (known positive and negative sample populations) and produce international reference standards, both of which are vital in establishing the necessary and detailed validation of any diagnostic test. Reference Laboratories act either singularly or in collaborative partnerships with other RLs or science institutes, but also, when required, and with impartiality, with the commercial sector, to ensure new tests are validated according to OIE standards. They promote and apply formal programmes of quality assurance (including proficiency testing programmes) for newly validated tests, ensuring ongoing monitoring and compliance with standards, or as required set out any limitations or uncertainties. Reference Laboratories publish information on test validation in the scientific literature and on relevant websites, as well as disseminating information at workshops and international conferences. Furthermore, they can offer training in the processes and systems underpinning test validation.

Dans le domaine de la validation des tests de diagnostic, les Laboratoires de référence de l'Organisation mondiale de la santé animale (OIE) jouent un rôle central et fournissent à la communauté internationale des conseils impartiaux ainsi qu'un soutien pour la sélection, la mise au point et la validation des tests de diagnostic utilisés pour la détection des maladies correspondant à leur domaine de spécialisation. Les Laboratoires de référence nationaux remplissent une fonction inestimable en facilitant l'introduction, la validation continue et l'application de tests de diagnostic validés conformément aux normes internationales. Ces laboratoires sont dotés de personnels expérimentés possédant une connaissance approfondie de ces systèmes et qui ont accès à des installations spécialisées pour mener à bien leurs opérations et suivre de près les changements ou les avancées technologiques. Ils peuvent ainsi examiner leur pertinence et intérêt au regard de l'évolution des exigences relatives aux tests de diagnostic. Le mandat des Laboratoires de référence recouvre souvent un large éventail d'activités reliant les programmes de recherche ou développement et les activités de surveillance, ce qui permet de réaliser une évaluation continue des outils diagnostiques et, si besoin, de procéder à leur amélioration. Les Laboratoires de référence entretiennent ou ont accès à des banques de matériels biologiques uniques (panels d'échantillons positifs et négatifs connus) et produisent des réactifs de référence internationale, deux catégories de matériels essentielles pour procéder à la validation point par point d'un test diagnostique suivant les critères requis. Les Laboratoires de référence interviennent individuellement ou en partenariat avec d'autres Laboratoires de référence ou instituts scientifiques, mais aussi, lorsque c'est nécessaire et dans le respect des règles d'impartialité, avec le secteur privé, afin de s'assurer que les nouveaux tests sont validés conformément aux normes de l'OIE. Ils soutiennent et appliquent des programmes officiels d'assurance de la qualité (y compris en participant à des programmes d'essais d'aptitude inter-laboratoires) pour les tests nouvellement validés et garantissent leur suivi continu ainsi que leur conformité avec les normes, ou, suivant les cas, définissent les limites ou le niveau d'incertitude à prendre en considération. Les Laboratoires de référence publient les données relatives à la validation des tests dans des journaux scientifique et sur les sites Web pertinents et diffusent également des informations sur le sujet lors d'ateliers et de conférences internationales. En outre, ils peuvent proposer des formations sur les procédures et les systèmes qui sous-tendent la validation des tests.

En el terreno de la validación de pruebas de diagnóstico, los Laboratorios de Referencia de la Organización Mundial de Sanidad Animal (OIE) cumplen una función central y proporcionan a la comunidad internacional servicios de apoyo y asesoramiento imparcial para la selección, el desarrollo y la validación de pruebas de diagnóstico, que pueden aplicarse a la enfermedad para la que cada laboratorio esté designado. Los laboratorios de referencia nacionales cumplen una inestimable función de apoyo a la implantación, la continua validación y la utilización de pruebas de diagnóstico validadas con arreglo a las normas internacionales. Disponen de personal experimentado y muy buen conocedor de estos sistemas y de acceso a instalaciones especializadas de trabajo, lo que les permite seguir de cerca los cambios o adelantos tecnológicos y estudiar su utilidad o interés en relación con la evolución de los requisitos de las pruebas de diagnóstico. Los Laboratorios de Referencia suelen tener un mandato amplio, que a los programas de investigación y desarrollo aúna actividades de vigilancia, en aras de la continua evaluación y, en caso necesario, mejora de las herramientas de diagnóstico. Estos laboratorios poseen (o tienen acceso a) archivos biológicos únicos (conjuntos de muestras probadamente positivas y negativas) y elaboran patrones de referencia internacional, elementos ambos indispensables para llevar a buen fin la necesaria validación detallada de toda prueba de diagnóstico. Los Laboratorios de Referencia pueden trabajar en solitario o en colaboración con otros Laboratorios de Referencia, con institutos científicos e incluso, cuando hace falta, y procediendo con imparcialidad, con entidades del sector privado, a fin de garantizar que toda nueva prueba sea validada con arreglo a las normas de la OIE. También promueven y llevan adelante programas oficiales de garantía de la calidad de pruebas recién validadas (incluidos programas de pruebas de competencia), lo que asegura un seguimiento continuo y el cumplimiento de la normativa en todo momento, o fijan, cuando es necesario, limitaciones o niveles de incertidumbre. Asimismo, estos laboratorios publican datos sobre la validación de pruebas en revistas científicas y sitios web conexos y difunden información al respecto en talleres y conferencias internacionales. Además, pueden impartir formación sobre los procesos y sistemas que fundamentan la validación de pruebas de diagnóstico.

De novo variants in MED12 cause X-linked syndromic neurodevelopmental disorders in 18 females.

PURPOSE: MED12 is a subunit of the Mediator multiprotein complex with a central role in RNA polymerase II transcription and regulation of cell growth, development, and differentiation. This might underlie the variable phenotypes in males carrying missense variants in MED12, including X-linked recessive Ohdo, Lujan, and FG syndromes. METHODS: By international matchmaking we assembled variant and clinical data on 18 females presenting with variable neurodevelopmental disorders (NDDs) and harboring de novo variants in MED12. RESULTS: Five nonsense variants clustered in the C-terminal region, two splice variants were found in the same exon 8 splice acceptor site, and 11 missense variants were distributed over the gene/protein. Protein truncating variants were associated with a severe, syndromic phenotype consisting of intellectual disability (ID), facial dysmorphism, short stature, skeletal abnormalities, feeding difficulties, and variable other abnormalities. De novo missense variants were associated with a less specific, but homogeneous phenotype including severe ID, autistic features, limited speech and variable other anomalies, overlapping both with females with truncating variants as well as males with missense variants. CONCLUSION: We establish de novo truncating variants in MED12 as causative for a distinct NDD and de novo missense variants as causative for a severe, less specific NDD in females.

Ageing of Polymer Frictional Interfaces: The Role of Quantity and Quality of Contact.

When two objects are in contact, the force necessary for one to start sliding over the other is larger than the force necessary to keep the sliding motion going. This difference between static and dynamic friction is thought to result from a reduction in the area of real contact upon the onset of slip. Here, we resolve the structure in the area of contact on the molecular scale by means of environment-sensitive molecular rotors using (super-resolution) fluorescence microscopy and fluorescence lifetime imaging. We demonstrate that the macroscopic friction force is not only controlled by the area of real contact but also controlled by the "quality" of that area of real contact, which determines the friction per unit contact area. We show that the latter is affected by the local density of the contacting surfaces, a parameter that can be expected to change in time at any interface that involves glassy, amorphous materials.

Correction: Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

This Article was originally published under a CC BY-NC-SA 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.

Frictional weakening of slip interfaces.

When two objects are in contact, the force necessary to overcome friction is larger than the force necessary to keep sliding motion going. This difference between static and dynamic friction is usually attributed to the growth of the area of real contact between rough surfaces in time when the system is at rest. We directly measure the area of real contact and show that it actually increases during macroscopic slip, despite the fact that dynamic friction is smaller than static friction. This signals a decrease in the interfacial shear strength, the friction per unit contact area, which is due to a mechanical weakening of the asperities. This provides a novel explanation for stick-slip phenomena in, e.g., earthquakes.

Associations between endocrine disrupting chemicals and equine metabolic syndrome phenotypes.

Equine Metabolic Syndrome (EMS) is characterized by abnormalities in insulin regulation, increased adiposity and laminitis, and has several similarities to human metabolic syndrome. A large amount of environmental variability in the EMS phenotype is not explained by commonly measured factors (diet, exercise, and season), suggesting that other environmental factors play a role in EMS development. Endocrine disrupting chemicals (EDCs) are associated with metabolic syndrome and other endocrine abnormalities in humans. This led us to hypothesize that EDCs are detectable in horse plasma and play a role in the pathophysiology of EMS. EDCs acting through the aryl hydrocarbon and estrogen receptors, were measured in plasma of 301 horses from 32 farms. The median (range) TEQ (2,3,7,8-TCDD equivalent) and EEQ (17ß-estradiol equivalent) were 19.29 pg/g (0.59-536.36) and 10.50 pg/ml (4.35-15000.00), respectively. TEQ was negatively associated with plasma fat extracted and batch analyzed. EEQ was positively associated with pregnancy and batch analyzed, and negatively associated with being male and superfund score ≤100 miles of the farm. Of particular interest, serum glucose and insulin, glucose and insulin post oral sugar challenge, and leptin concentrations were associated with EEQ, and serum triglyceride concentration was associated with TEQ. Overall, we demonstrated that EDCs are present in the plasma of horses and may explain some of the environmental variability in measured EMS phenotypes. This is the first example of EDCs being associated with clinical disease phenotype components in domestic animals.

Molecular probes reveal deviations from Amontons' law in multi-asperity frictional contacts.

Amontons' law defines the friction coefficient as the ratio between friction force and normal force, and assumes that both these forces depend linearly on the real contact area between the two sliding surfaces. However, experimental testing of frictional contact models has proven difficult, because few in situ experiments are able to resolve this real contact area. Here, we present a contact detection method with molecular-level sensitivity. We find that while the friction force is proportional to the real contact area, the real contact area does not increase linearly with normal force. Contact simulations show that this is due to both elastic interactions between asperities on the surface and contact plasticity of the asperities. We reproduce the contact area and fine details of the measured contact geometry by including plastic hardening into the simulations. These new insights will pave the way for a quantitative microscopic understanding of contact mechanics and tribology.

Light therapy: is it safe for the eyes?

OBJECTIVE: Light therapy has become an increasingly popular treatment for depression and a range of other neuropsychiatric conditions. Yet, concerns have been raised about the ocular safety of light therapy. METHOD: We conducted the first systematic review into the ocular safety of light therapy. A PubMed search on January 4, 2017, identified 6708 articles, of which 161 were full-text reviewed. In total, 43 articles reporting on ocular complaints and ocular examinations were included in the analyses. RESULTS: Ocular complaints, including ocular discomfort and vision problems, were reported in about 0% to 45% of the participants of studies involving light therapy. Based on individual studies, no evident relationship between the occurrence of complaints and light therapy dose was found. There was no evidence for ocular damage due to light therapy, with the exception of one case report that documented the development of a maculopathy in a person treated with the photosensitizing antidepressant clomipramine. CONCLUSION: Results suggest that light therapy is safe for the eyes in physically healthy, unmedicated persons. The ocular safety of light therapy in persons with preexisting ocular abnormalities or increased photosensitivity warrants further study. However, theoretical considerations do not substantiate stringent ocular safety-related contraindications for light therapy.

Passive surveillance of United Kingdom bats for lyssaviruses (2005-2015).

Passive surveillance for lyssaviruses in UK bats has been ongoing since 1987 and has identified 13 cases of EBLV-2 from a single species; Myotis daubentonii. No other lyssavirus species has been detected. Between 2005 and 2015, 10 656 bats were submitted, representing 18 species, creating a spatially and temporally uneven sample of British bat fauna. Uniquely, three UK cases originate from a roost at Stokesay Castle in Shropshire, England, where daily checks for grounded and dead bats are undertaken and bat carcasses have been submitted for testing since 2007. Twenty per cent of Daubenton's bats submitted from Stokesay Castle since surveillance began, have tested positive for EBLV-2. Phylogenetic analysis reveals geographical clustering of UK viruses. Isolates from Stokesay Castle are more closely related to one another than to viruses from other regions. Daubenton's bats from Stokesay Castle represent a unique opportunity to study a natural population that appears to maintain EBLV-2 infection and may represent endemic infection at this site. Although the risk to public health from EBLV-2 is low, consequences of infection are severe and effective communication on the need for prompt post-exposure prophylaxis for anyone that has been bitten by a bat is essential.