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•Largest and most diverse genetic study of plasma fibrinogen identifies 54 regions (18 novel), housing 69 distinct variants (20 novel).•Links to (1) liver enzyme, blood cell, and lipid genetic signals, (2) liver regulatory elements, and (3) thrombotic and inflammatory disease.

Improving the use of platinum in propane dehydrogenation catalysts is a crucial aspect to increasing the efficiency and sustainability of propylene production. A known and practiced strategy involves incorporating more abundant metals in supported platinum catalysts, increasing its activity and stability while decreasing the overall loading. Here, using colloidal techniques to control the size and composition of the active phase, we show that Pt/Cu alloy nanoparticles supported on alumina (Pt/Cu/Al2O3) displayed elevated rates for propane dehydrogenation at low temperature compared to a monometallic Pt/Al2O3catalyst. We demonstrate that the enhanced catalytic activity is correlated with a higher surface Cu content and formation of a Pt-rich core and Cu-rich shell that isolates Pt sites and increases their intrinsic activity. However, rates declined on stream because of dynamic metal diffusion processes that led to a more uniform alloy structure. This transformation was only partially inhibited by adding excess hydrogen to the feed stream. Instead, cobalt was introduced to provide trimetallic Pt/Cu/Co catalysts with stabilized surface structure and stable activity and higher rates than the original Pt/Cu system. The structure–activity relationship insights in this work offer improved knowledge of propane dehydrogenation catalyst development featuring reduced Pt loadings and notable thermal stability for propylene production.

Neighbourhood disadvantage may be associated with brain health but the importance of exposure at different stages of the life course is poorly understood. Utilising the Lothian Birth Cohort 1936, we explored the relationship between residential neighbourhood deprivation from birth to late adulthood, and global and local neuroimaging measures at age 73. A total of 689 participants had at least one valid brain measures (53% male); to maximise the sample size structural equation models with full information maximum likelihood were conducted. Residing in disadvantaged neighbourhoods in mid- to late adulthood was associated with smaller total brain (β= −0.06; SE = 0.02; sample size[N] = 658; number of pairwise complete observations[n]=390), grey matter (β= −0.11; SE = 0.03; N= 658; n= 390), and normal-appearing white matter volumes (β= −0.07; SE = 0.03; N= 658; n= 390), thinner cortex (β= −0.14; SE = 0.06; N= 636; n= 379), and lower general white matter fractional anisotropy (β= −0.19; SE = 0.06; N= 665; n= 388). We also found some evidence on the accumulating impact of neighbourhood deprivation from birth to late adulthood on age 73 total brain (β= −0.06; SE = 0.02; N= 658; n= 276) and grey matter volumes (β= −0.10; SE = 0.04; N= 658; n= 276). Local analysis identified affected focal cortical areas and specific white matter tracts. Among individuals belonging to lower social classes, the brain-neighbourhood associations were particularly strong, with the impact of neighbourhood deprivation on total brain and grey matter volumes, and general white matter fractional anisotropy accumulating across the life course. Our findings suggest that living in deprived neighbourhoods across the life course, but especially in mid- to late adulthood, is associated with adverse brain morphologies, with lower social class amplifying the vulnerability.

Solar thermochemical hydrogen production using redox-active metal oxides is a promising pathway for the production of green hydrogen and synthetic fuel precursors. Herein, the perovskite material (La0.6Sr0.4)0.95Mn0.8Ga0.2O3−δ(LSMG6482) is identified as a promising metal oxide for thermochemical water splitting. LSMG6482, along with more-established water splitters ceria and (La0.6Sr0.4)0.95MnxAl1–xO3−δ(LSMA) perovskites, is experimentally characterized via thermogravimetric (TGA) analysis and high-temperature water splitting in a reactor simulating solar concentrating conditions. TGA analysis demonstrated that LSMG6482 has high and stable oxygen exchange capacity under controlled pO2redox cycling, demonstrated by large changes in oxygen nonstoichiometry (δ) relative to ceria. Water splitting experiments using laser heating (Tred= 1400 °C, Tox= 1200 °C) resulted in H2yields of 165.1 μmol g–1for the candidate LSMG6482 composition, exceeding that of all benchmark materials tested. Under high conversion oxidation conditions, where H2is cointroduced with H2O (150 ≤ nH2O/nH2≤ 500), H2yields were greatest for LSMG6482 and LSMA6482, up to four times that of ceria at the highest nH2O/nH2conditions. Crystallographic analysis showed that over the course of experimentation, there is some secondary phase growth for all perovskite compositions, except for LSMA6482, but there was no observable degradation in H2yields.

Aurora A kinase, a cell division regulator, is frequently overexpressed in various cancers, provoking genome instability and resistance to antimitotic chemotherapy. Localization and enzymatic activity of Aurora A are regulated by its interaction with the spindle assembly factor TPX2. We have used fragment-based, structure-guided lead discovery to develop small molecule inhibitors of the Aurora A-TPX2 protein–protein interaction (PPI). Our lead compound, CAM2602, inhibits Aurora A:TPX2 interaction, binding Aurora A with 19 nM affinity. CAM2602exhibits oral bioavailability, causes pharmacodynamic biomarker modulation, and arrests the growth of tumor xenografts. CAM2602acts by a novel mechanism compared to ATP-competitive inhibitors and is highly specific to Aurora A over Aurora B. Consistent with our finding that Aurora A overexpression drives taxane resistance, these inhibitors synergize with paclitaxel to suppress the outgrowth of pancreatic cancer cells. Our results provide a blueprint for targeting the Aurora A-TPX2 PPI for cancer therapy and suggest a promising clinical utility for this mode of action.

SUMMARYDiagnostic systems are not conducive to compassionate health-bringing psychiatric treatment. The systems were built around the fallacy that the politics of biomedicine could be reliably applied to the emergent properties of human psychological suffering and enable diagnosis-specific treatment packages. The resulting industrialised medicine, which reified people, failed to facilitate the compassion needed for healing. This article outlines an approach to psychiatric practice that involves understanding children's suffering and vulnerabilities in terms of their attachment strategies and adaptation to their context and takes a mindful approach to developing compassionate collaborative treatment goals (intelligent kindness). A shift towards mindful psychiatric medicine would encourage politicians to serve the people by addressing the contexts associated with human suffering and what makes people vulnerable, especially social inequalities. Healthy societies in which the psychiatric dis-ease of the population is adequately addressed will not be built with limited biomedical understanding of dis-ease.

Pulmonary fibrosis results from alveolar injury, leading to extracellular matrix remodelling and impaired lung function. This study aimed to classify patients with pulmonary fibrosis according to blood biomarkers to differentiate distinct disease patterns, known as endotypes.

SummaryBowlby remained attached to his psychoanalytic roots and conceptualised treatment in terms of one-to-one relationships, albeit acknowledging the need for a family formulation. Bowlby's five therapeutic tasks were never adapted to the current understanding of working with the relationships fostering the development and maintenance of children's attachment strategies. This paper goes through each of Bowlby's five tasks and adapts them to our current understanding of development, with consequences for prioritising family approaches, rather than a secure base alone with a therapist. In doing so I will review the process of achieving security, seeing it as more similar to an allostatic process than a state of homeostasis.

Background: Anastomotic leak after esophagectomy is a major contributor to surgery-related morbidity and mortality. The purpose of this systematic review was to evaluate if positive-smoking status is associated with the incidence of this complication. Methods: A systematic search of MEDLINE, EMBASE, Scopus, Web of Science and Cochrane Library was performed on April 4th, 2023. Inclusion criteria comprised human participants undergoing esophagectomy, age ≥ 18, n≥ 5, and identification of smoking status. The primary outcome was incidence of anastomotic leak. Sub-group analysis by ex- or current smoking status was performed. Meta-analysis was performed with RevMan 5.4.1 using a Mantel–Haenszel random-effects model. Publication bias was evaluated visually with funnel plots and through the Egger test. Results: A total of 220 abstracts were screened, of which 69 full-text studies were assessed for eligibility, with 13 studies selected for final inclusion. This included 16,103 patients, of which 4433 were ex- or current smokers, and 9141 were never smokers. Meta-analysis revealed an increased odds of anastomotic leak in patients with a positive-smoking status (current or ex-smokers) compared to never smokers (OR 1.44, 95% CI 1.18–1.76, I2= 44%, p< 0.001. Meta-analysis of six studies comparing active smokers alone to never smokers identified a significant increased odds of anastomotic leak (OR 1.80, 95% CI 1.25–2.59, p= 0.002, I2= 0%). Meta-analysis of five studies comparing ex-smokers to never smokers identified a significant increased odds of anastomotic leak (OR 1.36, 95% CI 1.02–1.82, p= 0.04, I2= 0%). The odds of anastomotic leak decreased among ex-smokers compared to active smokers. Conclusion: The findings of this systematic review and meta-analysis support the association between positive-smoking status and the risk of anastomotic leak after esophagectomy. Results further emphasize the importance of preoperative smoking cessation to reduce post-operative morbidity.

Metal phosphide-containing materials have emerged as a potential candidate of nonprecious metal-based catalysts for alkaline oxygen evolution reaction (OER). While it is known that metal phosphide undergoes structural evolution, considerable debate persists regarding the effects of dynamics on the surface activation and morphological stability of the catalysts. In this study, we synthesize NiPx-FeOxcore–shell nanocatalysts with an amorphous NiPxcore designed for enhanced OER activity. Using ex situX-ray absorption spectroscopy, we elucidate the local structural changes as a function of the cyclic voltammetry cycles. Our studies suggest that the presence of corner-sharing octahedra in the FeOxshell improves structural rigidity through interlayer cross-linking, thereby inhibiting the diffusion of OH–/H2O. Thus, the FeOxshell preserves the amorphous NiPxcore from rapid oxidation to Ni3(PO4)2and Ni(OH)2. On the other hand, the incorporation of Ni from the core into the FeOxshell facilitates absorption of hydroxide ions for OER. As a result, Ni/Fe(OH)xat the surface oxidizes to the active γ-(oxy)hydroxide phase under the applied potentials, promoting OER. This intriguing synergistic behavior holds significance as such a synthetic route involving the FeOxshell can be extended to other systems, enabling manipulation of surface adsorption and diffusion of hydroxide ions. These findings also demonstrate that nanomaterials with core–shell morphologies can be tuned to leverage the strength of each metallic component for improved electrochemical activities.

The study of complex behaviors is often challenging when using manual annotation due to the absence of quantifiable behavioral definitions and the subjective nature of behavioral annotation. Integration of supervised machine learning approaches mitigates some of these issues through the inclusion of accessible and explainable model interpretation. To decrease barriers to access, and with an emphasis on accessible model explainability, we developed the open-source Simple Behavioral Analysis (SimBA) platform for behavioral neuroscientists. SimBA introduces several machine learning interpretability tools, including SHapley Additive exPlanation (SHAP) scores, that aid in creating explainable and transparent behavioral classifiers. Here we show how the addition of explainability metrics allows for quantifiable comparisons of aggressive social behavior across research groups and species, reconceptualizing behavior as a sharable reagent and providing an open-source framework. We provide an open-source, graphical user interface (GUI)-driven, well-documented package to facilitate the movement toward improved automation and sharing of behavioral classification tools across laboratories.

Study Design Systematic Review and Meta-Analysis.Objective Identify the incidence, mechanism of injury, investigations, management, and outcomes of Vertebral Artery Injury (VAI) after cervical spine trauma.Methods A systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines (PROSPERO-ID CRD42021295265). Three databases were searched (PubMed, SCOPUS, Google Scholar, CINAHL PLUS). Incidence of VAI, investigations to diagnose (Computed Tomography Angiography, Digital Subtraction Angiography, Magnetic Resonance Angiography), stroke incidence, and management paradigms (conservative, antiplatelets, anticoagulants, surgical, endovascular treatment) were delineated. Incidence was calculated using pooled proportions random effects meta-analysis.Results A total of 44 studies were included (1777 patients). 20-studies (n = 503) included data on trauma type; 75.5% (n = 380) suffered blunt trauma and 24.5% (n = 123) penetrating. The overall incidence of VAI was .95% (95% CI 0.65-1.29). From the 16 studies which reported data on outcomes, 8.87% (95% CI 5.34- 12.99) of patients with VAI had a posterior stroke. Of the 33 studies with investigation data, 91.7% (2929/3629) underwent diagnostic CTA; 7.5% (242/3629) underwent MRA and 3.0% (98/3629) underwent DSA. Management data from 20 papers (n = 475) showed 17.9% (n = 85) undergoing conservative therapy, anticoagulation in 14.1% (n = 67), antiplatelets in 16.4% (n = 78), combined therapy in 25.5% (n = 121) and the rest (n = 124) managed using surgical and endovascular treatments.Conclusion VAI in cervical spine trauma has an approximate posterior circulation stroke risk of 9%. Optimal management paradigms for the prevention and management of VAI are yet to be standardized and require further research.

The fundamental interest in actinide chemistry, particularly for the development of thorium-based materials, is experiencing a renaissance owing to the recent and rapidly growing attention to fuel cycle reactors, radiological daughters for nuclear medicine, and efficient nuclear stockpile development. Herein, we uncover fundamental principles of thorium chemistry on the example of Th-based extended structures such as metal–organic frameworks in comparison with the discrete systems and zirconium extended analogs, demonstrating remarkable over two-and-half-year chemical stability of Th-based frameworks as a function of metal node connectivity, amount of defects, and conformational linker rigidity through comprehensive spectroscopic and crystallographic analysis as well as theoretical modeling. Despite exceptional chemical stability, we report the first example of studies focusing on the reactivity of the most chemically stable Th-based frameworks in comparison with the discrete Th-based systems such as metal–organic complexes and a cage, contrasting multicycle recyclability and selectivity (>97%) of the extended structures in comparison with the molecular compounds. Overall, the presented work not only establishes the conceptual foundation for evaluating the capabilities of Th-based materials but also represents a milestone for their multifaceted future and foreshadows their potential to shape the next era of actinide chemistry.

The reduction of CO2is known to promote increased alkene yields from alkane dehydrogenations when the reactions are cocatalyzed. The mechanism of this promotion is not understood in the context of catalyst active-site environments because CO2is amphoteric, and even general aspects of the chemistry, including the significance of competing side reactions, differ significantly across catalysts. Atomically dispersed chromium cations stabilized in highly siliceous MFI zeolite are shown here to enable the study of the role of parallel CO2reduction during ethylene-selective ethane dehydrogenation. Based on infrared spectroscopy and X-ray absorption spectroscopy data interpreted through calculations using density functional theory (DFT), the synthesized catalyst contains atomically dispersed Cr cations stabilized by silanol nests in micropores. Reactor studies show that cofeeding CO2increases stable ethylene-selective ethane dehydrogenation rates over a wide range of partial pressures. OperandoX-ray absorption near-edge structure (XANES) and extended X-ray absorption fine-structure (EXAFS) spectra indicate that during reaction at 650 °C the Cr cations maintain a nominal 2+ charge and a total Cr–O coordination number of approximately 2. However, CO2reduction induces a change, correlated with the CO2partial pressure, in the populationof two distinct Cr–O scattering paths. This indicates that the promotional effect of parallel CO2reduction can be attributed to a subtle change in Cr–O bond lengths in the local coordination environment of the active site. These insights are made possible by simultaneously fitting multiple EXAFS spectra recorded in different reaction conditions; this novel procedure is expected to be generally applicable for interpreting operandocatalysis EXAFS data.

Savolitinib is a compound that can crystallize in an undesirable, high aspect ratio needle morphology. This morphology type may cause issues in downstream processing. This paper demonstrates a unique method to alter the crystal morphology of savolitinib to make it more processable, resulting in the active pharmaceutical ingredient (API) crystallizing out in considerably more processable stellates. The volatile deep eutectic solvent technique presents a simple and scalable method for changing the crystal morphology while maintaining the polymorph of the API in this case, confirmed via powder X-ray diffraction and differential scanning calorimetry analysis.

Medical emergency team (METs), activated by vital sign–based calling criteria respond to deteriorating patients in the hospital setting. Calling criteria may be altered where clinicians feel this is appropriate. Altered calling criteria (ACC) has not previously been evaluated in the emergency department (ED) setting.

Strong metal–support interactions (SMSIs) are well-known in the field of heterogeneous catalysis to induce the encapsulation of platinum (Pt) group metals by oxide supports through high temperature H2reduction. However, demonstrations of SMSI overlayers have largely been limited to reducible oxides, such as TiO2and Nb2O5. Here, we show that the amorphous native surface oxide of plasmonic aluminum nanocrystals (AlNCs) exhibits SMSI-induced encapsulation of Pt following reduction in H2in a Pt structure dependent manner. Reductive treatment in H2at 300 °C induces the formation of an AlOxSMSI overlayer on Pt clusters, leaving Pt single-atom sites (Ptiso) exposed available for catalysis. The remaining exposed Ptisospecies possess a more uniform local coordination environment than has been observed on other forms of Al2O3, suggesting that the AlOxnative oxide of AlNCs presents well-defined anchoring sites for individual Pt atoms. This observation extends our understanding of SMSIs by providing evidence that H2-induced encapsulation can occur for a wider variety of materials and should stimulate expanded studies of this effect to include nonreducible oxides with oxygen defects and the presence of disorder. It also suggests that the single-atom sites created in this manner, when combined with the plasmonic properties of the Al nanocrystal core, may allow for site-specific single-atom plasmonic photocatalysis, providing dynamic control over the light-driven reactivity in these systems.

Soft-oxidant-assisted methane coupling has emerged as a promising pathway to upgrade methane from natural gas sources to high-value commodity chemicals, such as ethylene, at selectivities higher than those associated with oxidative (O2) methane coupling (OCM). To date, few studies have reported investigations into the electronic structure and the microscopic physical structure of catalytic active sites present in the binary metal oxide catalyst systems that are known to be effective for this reaction. Correlating the catalyst activity to specific active site structures and electronic properties is an essential aspect of catalyst design. Here, we used X-ray absorption spectroscopy at the Ca K-edge to ascertain the most probable local environment of Ca in the ZnO-supported Ca oxide catalysts. These catalysts are shown here to be active for N2O-assisted methane coupling (N2O-OCM) and have previously been reported to be active for CO2-assisted methane coupling (CO2-OCM). X-ray absorption near edge structure features at multiple Ca loadings are interpreted through simulated spectra derived from ab initiofull multiple scattering calculations. These simulations included consideration of CaO structures organized in multiple spatial arrangements─linear, planar, and cubic─with separate analyses of Ca atoms in the surfaces and bulk of the three-dimensional structures. The morphology of the oxide clusters was found to influence the various regions of the X-ray absorption spectrum differently. Experiment and theory show that for low-Ca-loading catalysts (≤1 mol %), which contain sites particularly active for methane coupling, Ca primarily exists in an oxidized state that is consistent with the coordination environment of Ca ions in one- and two-dimensional clusters. In addition to their unique nanoscale structures, the spectra also indicate that these clusters have varying degrees of undercoordinated surface Ca atoms that could further influence their catalytic activities. The local Ca structure was correlated to methane coupling activity from N2O-OCM and previously reported CO2-OCM reactor studies. This study provides a unique perspective on the relationship between the catalyst physical and electronic structure and active sites for soft-oxidant-assisted methane coupling, which can be used to inform future catalyst development.

AbstractWholesale markets, wholesalers, and processors play critical but underappreciated roles in shaping food systems. Most conventional research on food provisioning analyzes value chains in terms of their structure, conduct, and performance. We contend that a practices lens can illuminate how food systems are produced and reproduced through the emergence of new wholesale practices relating to quality, trust, and risk, and provide more nuanced understandings of how markets and trading shape and are shaped by food system transformations. Applying a practices lens to the analysis of these changes can help identify new ways of steering food systems toward more sustainable outcomes.

Sequence variation observed in populations of pathogens can be used for important public health and evolutionary genomic analyses, especially outbreak analysis and transmission reconstruction. Identifying this variation is typically achieved by aligning sequence reads to a reference genome, but this approach is susceptible to reference biases and requires careful filtering of called genotypes. There is a need for tools that can process this growing volume of bacterial genome data, providing rapid results, but that remain simple so they can be used without highly trained bioinformaticians, expensive data analysis, and long-term storage and processing of large files. Here we describe split k-mer analysis (SKA2), a method that supports both reference-free and reference-based mapping to quickly and accurately genotype populations of bacteria using sequencing reads or genome assemblies. SKA2 is highly accurate for closely related samples, and in outbreak simulations, we show superior variant recall compared with reference-based methods, with no false positives. SKA2 can also accurately map variants to a reference and be used with recombination detection methods to rapidly reconstruct vertical evolutionary history. SKA2 is many times faster than comparable methods and can be used to add new genomes to an existing call set, allowing sequential use without the need to reanalyze entire collections. With an inherent absence of reference bias, high accuracy, and a robust implementation, SKA2 has the potential to become the tool of choice for genotyping bacteria. SKA2 is implemented in Rust and is freely available as open-source software.

BackgroundMost schwannomas are isolated tumours occurring in otherwise healthy people. However, bilateral vestibular schwannomas (BVS) or multiple non-vestibular schwannomas indicate an underlying genetic predisposition. This is most commonly NF2-related schwannomatosis (SWN), but when BVS are absent, this can also indicate SMARCB1-related or LZTR1-related SWN.MethodsWe assessed the variant detection rates for the three major SWN genes (NF2, LZTR1and SMARCB1) in 154 people, from 150 families, who had at least one non-vestibular schwannoma, but who did not meet clinical criteria for NF2-related SWN at the time of genetic testing.ResultsWe found that 17 (11%) people from 13 families had a germline SMARCB1variant and 19 (12%) unrelated individuals had a germline LZTR1variant. 19 people had an NF2variant, but 18 of these were mosaic and 17 were only detected when 2 tumours were available for testing. The overall detection rate was 25% using blood alone, but increased to 36% when tumour analysis was included. Another 12 people had a germline variant of uncertain significance (VUS).ConclusionsThere were similar proportions of LZTR1, SMARCB1or mosaic NF2. However, since an NF2variant was detected in tumours from 103 people, it is likely that further cases of mosaicism would be detected if more people had additional tumours available for analysis. In addition, if further evidence becomes available to show that the VUSs are pathogenic, this would significantly increase the proportion of people with a genetic diagnosis. Our results indicate the importance of comprehensive genetic testing and improved variant classification.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence1. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy; however, responses are typically short lived1,2. Thus, there is an urgent need to develop more effective treatments. Components of the PI3K pathway represent plausible therapeutic targets; more than 70% of TNBCs have alterations in PIK3CA, AKT1 or PTEN3–6. However, in contrast to hormone-receptor-positive tumours, it is still unclear whether or how triple-negative disease will respond to PI3K pathway inhibitors7. Here we describe a promising AKT-inhibitor-based therapeutic combination for TNBC. Specifically, we show that AKT inhibitors synergize with agents that suppress the histone methyltransferase EZH2 and promote robust tumour regression in multiple TNBC models in vivo. AKT and EZH2 inhibitors exert these effects by first cooperatively driving basal-like TNBC cells into a more differentiated, luminal-like state, which cannot be effectively induced by either agent alone. Once TNBCs are differentiated, these agents kill them by hijacking signals that normally drive mammary gland involution. Using a machine learning approach, we developed a classifier that can be used to predict sensitivity. Together, these findings identify a promising therapeutic strategy for this highly aggressive tumour type and illustrate how deregulated epigenetic enzymes can insulate tumours from oncogenic vulnerabilities. These studies also reveal how developmental tissue-specific cell death pathways may be co-opted for therapeutic benefit.

Pd catalysts are highly active for CO oxidation but suffer from inhibition by NO at low temperatures (<150 °C). We posit that incorporation of Cu into the Pd catalyst will improve low-temperature CO oxidation activity and reduce inhibition from competitive adsorbers. To probe this hypothesis, a series of PdCu alloys with different Pd : Cu ratios were synthesized and tested in the temperature-programmed oxidation of CO in the presence and absence of NO. Incorporation of small amounts of Cu into Pd improves the reactivity, as well as the resistance to NO inhibition. Beyond this, Cu incorporation into the Pd has a detrimental effect on the activity for CO oxidation. Based on combined infrared and X-ray absorption spectroscopy studies, we show that high activity and resistance to inhibition requires alloying of Pd and Cu and the formation of a diverse surface, while surface segregation of Cu results in poor activity and inhibition.

BackgroundRare cystic lung diseases are increasingly recognised due the wider application of CT scanning making cystic lung disease management a growing part of respiratory care. Cystic lung diseases tend to have extrapulmonary features that can both be diagnostic but also require surveillance and treatment in their own right. As some of these diseases now have specific treatments, making a precise diagnosis is crucial. While Langerhans cell histiocytosis, Birt-Hogg-Dubé syndrome, lymphoid interstitial pneumonia and lymphangioleiomyomatosis are becoming relatively well-known diseases to respiratory physicians, a targeted and thorough workup improves diagnostic accuracy and may suggest other ultrarare diseases such as light chain deposition disease, cystic pulmonary amyloidosis, low-grade metastatic neoplasms or infections. In many cases, diagnostic information is overlooked leaving uncertainty over the disease course and treatments.AimsThis position statement from the Rare Disease Collaborative Network for cystic lung diseases will review how clinical, radiological and physiological features can be used to differentiate between these diseases.NarrativeWe highlight that in many cases a multidisciplinary diagnosis can be made without the need for lung biopsy and discuss where tissue sampling is necessary when non-invasive methods leave diagnostic doubt. We suggest an initial workup focusing on points in the history which identify key disease features, underlying systemic and familial diseases and a clinical examination to search for connective tissue disease and features of genetic causes of lung cysts. All patients should have a CT of the thorax and abdomen to characterise the pattern and burden of lung cysts and extrapulmonary features and also spirometry, gas transfer and a 6 min walk test. Discussion with a rare cystic lung disease centre is suggested before a surgical biopsy is undertaken.ConclusionsWe suggest that this focused workup should be performed in all people with multiple lung cysts and would streamline referral pathways, help guide early treatment, management decisions, improve patient experience and reduce overall care costs. It could also potentially catalyse a national research database to describe these less well-understood and unidentified diseases, categorise disease phenotypes and outcomes, potentially leading to better prognostic data and generating a stronger platform to understand specific disease biology.

Almost all high spatial resolution positron emission tomography (PET) detectors based on pixelated scintillator arrays utilize crystal arrays with smaller pitches than photodetector arrays, leading to challenges in resolving edge crystals. To address this issue, this article introduces a novel multi-resolution silicon photomultiplier (SiPM) array design aimed at decreasing the number of readout channels required while maintaining the crystal resolvability of the detector, especially for edge crystals. The performance of a pseudo $9\times9$ multi-resolution SiPM array, consisting of $6.47\times6.47$ mm 2, $6.47\times3.07$ mm 2, and $3.07\times3.07$ mm2 SiPMs, was compared to those of a pseudo $8\times8$ SiPM array with a 6.8-mm pitch, and a $16\times16$ SiPM array with a 3.4-mm pitch using a $36\times36$ LYSO array with a pitch of 1.5 mm. The large-size pseudo SiPMs were implemented by digitally grouping multiple $3.07\times3.07$ mm2 SiPMs. The flood histograms show that the edge crystal resolvability of the pseudo $9\times9$ multi-resolution SiPM array is comparable to that of the $16\times16$ SiPM array and is significantly better than that of the $8\times8$ SiPM array.

Non-overlapping codes have been studied for almost 60 years. In such a code, no proper, non-empty prefix of any codeword is a suffix of any codeword. In this paper, we study codes in which overlaps of certain specified sizes are forbidden. We prove some general bounds and we give several constructions in the case of binary codes. Our techniques also allow us to provide an alternative, elementary proof of a lower bound on non-overlapping codes due to Levenshtein (1964).

The One Health concept has acquired increasing attention due to the COVID-19 pandemic. We argue for a health promotion perspective that frames One Health in terms of positive health for people, animals, and ecosystems and includes a spiritual-cosmological dimension. This would enhance policy, research, and practice across disciplines and sectors for a more resilient and harmonious planet.