How should the Defence Medical Services prepare for an Article 5 NATO collective defence operation with the prospect of high volumes of combat casualties?

Since the February 2022 Russian invasion of Ukraine, the prospect of an Article 5 North Atlantic Treaty Organisation collective defence operation in Europe has increased significantly. Were this type of operation to occur, it would present different challenges to the Defence Medical Services (DMS) than those of the era of the International Security Assistance Force in Afghanistan, where air superiority was assured, and combat casualty numbers did not approach the tens of thousands experienced by Russia and Ukraine in the first months following the invasion. This essay examines how the DMS could prepare for such an operation using four key themes: preparing for prolonged field care, training medical personnel for combat, recruiting and retaining medical personnel and planning for post-traumatic stress disorder.

Unstructured Data Are Superior to Structured Data for Eliciting Quantitative Smoking History From the Electronic Health Record.

PURPOSE: Develop a method for extracting smoking status and quantitative smoking history from clinician notes to facilitate cohort identification for low-dose computed tomography (LDCT) scanning for early detection of lung cancer. MATERIALS AND METHODS: A sample of 4,615 adult patients were randomly selected from the Multiparameter Intelligent Monitoring in Critical Care (MIMIC-III) database. The structured data were obtained by queries of the diagnosis tables using the International Classification of Diseases codes in use at that time. Unstructured data were drawn from clinician notes via natural language processing (NLP) using named entity recognition and our clinical data processing and extraction algorithms to identify two main clinical criteria for each smoking patient: (1) pack years smoked and (2) time from quit date (if applicable). A subset of 10% of the patient charts were manually reviewed for accuracy and precision. RESULTS: The structured data revealed 575 (12.5%) ever smokers (current plus past use). None of these patients had quantification of their smoking history, and 4,040 (87.5%) had no smoking information in the diagnosis tables; consequently, a cohort of patients eligible for LDCT could not be determined. Review of the physician notes by NLP disclosed 1,930 (41.8%) ever smokers of whom 537 were active smokers and 1,299 former smokers, and in 94 cases, it could not be determined if they were active or former smokers. A total of 1365 patients (29.6%) had no smoking data recorded. When the smoking and the age criteria for LDCT were applied to this group, 276 were found to be eligible for LDCT using the USPSTF criteria. As determined by clinician review, our F-score for identifying patients eligible for LDCT was 0.88. CONCLUSION: Unstructured data, obtained by NLP, can accurately identify a precise cohort that meets the USPSTF guidelines for LDCT.

Ab Initio Investigation of the Na3[Ln(ODA)3]·2NaClO4·6H2O (Ln = Ce-Yb; ODA = Oxydiacetate) Series.

In this work, the Na3[Ln(ODA)3]·2NaClO4·6H2O (Ln = Ce-Yb; ODA = oxydiacetate) series was analyzed with the ab initio ligand field theory (AILFT) module of the ORCA computational suite. The results were discussed within the framework of the angular overlap model (AOM) and compared to literature data. We find that the structural changes observed across the series exemplifies the effects of the lanthanide contraction also manifesting in the value of the AOM parameters. It is also shown that the complete active space self-consistent field (CASSCF) methodology is sufficient to describe the ligand field interactions in mononuclear lanthanide complexes, and the effects of dynamic correlation, through n-electron valence state perturbation theory (NEVPT2), are discussed. The calculated ligand field parameters of the present work are compared to the experimentally derived values from the literature.

Temporal trends in associations between severe mental illness and risk of cardiovascular disease: A systematic review and meta-analysis.

BACKGROUND: Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and CVD-related mortality. To date, no systematic review has investigated changes in population level CVD-related mortality over calendar time. It is unclear if this relationship has changed over time in higher-income countries with changing treatments. METHODS AND FINDINGS: To address this gap, a systematic review was conducted, to assess the association between SMI and CVD including temporal change. Seven databases were searched (last: November 30, 2021) for cohort or case-control studies lasting ≥1 year, comparing frequency of CVD mortality or incidence in high-income countries between people with versus without SMI. No language restrictions were applied. Random effects meta-analyses were conducted to compute pooled hazard ratios (HRs) and rate ratios, pooled standardised mortality ratios (SMRs), pooled odds ratios (ORs), and pooled risk ratios (RRs) of CVD in those with versus without SMI. Temporal trends were explored by decade. Subgroup analyses by age, sex, setting, world region, and study quality (Newcastle-Ottawa scale (NOS) score) were conducted. The narrative synthesis included 108 studies, and the quantitative synthesis 59 mortality studies (with (≥1,841,356 cases and 29,321,409 controls) and 28 incidence studies (≥401,909 cases and 14,372,146 controls). The risk of CVD-related mortality for people with SMI was higher than controls across most comparisons, except for total CVD-related mortality for BD and cerebrovascular accident (CVA) for mixed SMI. Estimated risks were larger for schizophrenia than BD. Pooled results ranged from SMR = 1.55 (95% confidence interval (CI): 1.33 to 1.81, p < 0.001), for CVA in people with BD to HR/rate ratio = 2.40 (95% CI: 2.25 to 2.55, p < 0.001) for CVA in schizophrenia. For schizophrenia and BD, SMRs and pooled HRs/rate ratios for CHD and CVD mortality were larger in studies with outcomes occurring during the 1990s and 2000s than earlier decades (1980s: SMR = 1.14, 95% CI: 0.57 to 2.30, p = 0.71; 2000s: SMR = 2.59, 95% CI: 1.93 to 3.47, p < 0.001 for schizophrenia and CHD) and in studies including people with younger age. The incidence of CVA, CVD events, and heart failure in SMI was higher than controls. Estimated risks for schizophrenia ranged from HR/rate ratio 1.25 (95% CI: 1.04 to 1.51, p = 0.016) for total CVD events to rate ratio 3.82 (95% CI: 3.1 to 4.71, p < 0.001) for heart failure. Incidence of CHD was higher in BD versus controls. However, for schizophrenia, CHD was elevated in higher-quality studies only. The HR/rate ratios for CVA and CHD were larger in studies with outcomes occurring after the 1990s. Study limitations include the high risk of bias of some studies as they drew a comparison cohort from general population rates and the fact that it was difficult to exclude studies that had overlapping populations, although attempts were made to minimise this. CONCLUSIONS: In this study, we found that SMI was associated with an approximate doubling in the rate ratio of CVD-related mortality, particularly since the 1990s, and in younger groups. SMI was also associated with increased incidence of CVA and CHD relative to control participants since the 1990s. More research is needed to clarify the association between SMI and CHD and ways to mitigate this risk.

Scleroderma Renal Crisis Associated With Microangiopathic Hemolytic Anemia in a Patient With Seronegative Scleroderma and Monoclonal Gammopathy.

Systemic sclerosis with negative serology, particularly that complicated by scleroderma renal crisis (SRC), is rarely encountered. We describe a patient with seronegative systemic sclerosis who developed acute kidney injury, proteinuria, and hypertensive emergency following motor vehicle-related trauma and in the setting of nonsteroidal anti-inflammatory drug use. Findings on physical examination, imaging, and skin biopsy led to a clinical diagnosis of scleroderma, despite the lack of supportive laboratory data. IgG lambda paraproteinemia was detected on workup. Bone marrow biopsy showed plasmacytosis and trace lambda-restricted plasma cells consistent with monoclonal gammopathy of undetermined significance. Chemotherapy was initially started given concern for myeloma with cast nephropathy but was later stopped after a kidney biopsy revealed thrombotic microangiopathy (TMA). The SRC associated with TMA was ultimately diagnosed, though atypical hemolytic uremic syndrome (aHUS) induced perhaps by monoclonal gammopathy or hypertension was also possible. Captopril and eculizumab were initiated for SRC and aHUS, respectively. Despite therapy, renal function did not recover, and the patient required hemodialysis indefinitely. This case highlights clinical features common to both SRC and aHUS as well as points out a few ways to differentiate between them.

Transthyretin amyloidosis and herpes zoster infection: a mimic of temporal arteritis.

We describe the case of a patient who presented with symptoms of persistent headaches, left-sided facial pain and blurry vision of the left eye. The patient had recovered from a herpes zoster infection of the V1 division of the trigeminal nerve 1 month prior. Serum inflammatory markers were elevated, raising concern for temporal arteritis. Empiric high-dose prednisone was initiated. Bilateral temporal artery biopsies were performed but did not show evidence of vasculitis or multinucleated giant cells. Instead, extracellular material deposits were present within the vessel walls. Congo red staining was diagnostic for amyloidosis. Liquid chromatography and mass spectrometry identified the amyloid fibrils to be transthyretin-type (ATTR) consistent with age-related amyloidosis. Temporal artery involvement of amyloidosis is rare but when present is most often due to light chain amyloidosis. Based on our review of the literature, only a few cases of temporal artery ATTR amyloidosis have been reported.

Patient Perception of Cardiovascular Risk in Rheumatoid Arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have higher incidence of cardiovascular diseases (CVDs) compared with age- and sex-matched controls. The objective of our study was to measure the knowledge of patients with RA about the association between their disease and cardiovascular (CV) risk and to measure the frequency of counseling by physicians based on patient report. METHODS: A telephone survey was conducted among patients with RA enrolled in the Consortium of Rheumatology Researchers of North America RA registry to collect data on medical and social history and on knowledge about CVD risk in RA and how they learned about that risk. Multivariable logistic regression models were performed to determine the factors associated with patients' knowledge and factors influencing likelihood of physician counseling. The odds ratios (ORs) represent adjusted multivariable results. RESULTS: Of 185 patients with RA included in the study, 87 patients (47%) were aware that RA was a CV risk factor. Older age (OR 0.6; 95% confidence interval [CI] 0.4-0.8 per decade) and smoking (OR 0.4; 95% CI 0.1-0.9) were associated with low awareness, whereas disease duration of more than 10 years (OR 5.2; 95% CI 2.2-12.1) was positively associated with patient knowledge. Counseling by physicians, mostly rheumatologists, on CV risk in RA was reported by 47 patients (25%). Disease duration of more than 10 years (OR 3.9; 95% CI 1.2-13.1) was positively associated with patient-reported counseling. Patients with hypertension were less likely to report counseling (OR 0.4; 95% CI 0.2-0.9). CONCLUSION: Our study demonstrated low patient awareness of CV risk with RA and low rates of patient-reported counseling by physicians. This is an unmet need in clinical practice, which may be overcome by multimodal approaches such as developing websites, organizing symposiums, and involving health care providers at various levels.

Concomitant presentation of IgG4-negative idiopathic retroperitoneal fibrosis and Addison's disease.

We describe a patient who was admitted to our medical centre with acute renal failure, hyponatraemia and hyperkalaemia. CT of the abdomen and pelvis showed a retroperitoneal mass with bilateral ureteral obstruction. Biopsy revealed fibrosis with inflammatory infiltrate, but rare IgG4-positive plasma cells. After placement of bilateral pigtail nephrostomy catheters, renal failure improved but metabolic derangements remained. Morning serum cortisol level was equivocal, but with blunted response on cosyntropin stimulation testing indicating adrenal insufficiency. Serology for 21-hydroxylase antibodies was strongly positive, supporting the diagnosis of Addison's disease. In addition to nephrostomy catheters for obstructive uropathy, idiopathic retroperitoneal fibrosis was treated with mycophenolate mofetil. Physiological doses of hydrocortisone and fludrocortisone for Addison's disease were also initiated. The patient continues to be monitored for regression of the mass. Based on review of the literature, this is the first reported case of IgG4-negative idiopathic retroperitoneal fibrosis presenting with autoimmune primary adrenal insufficiency.

Scaling the Peaks Research Protocol: understanding the barriers and drivers to providing and using dementia-friendly community services in rural areas-a mixed methods study.

INTRODUCTION: Scaling the Peaks is a cross-disciplinary research study that draws on medical ethnography, human geography and Geospatial Information Science (GIS) to address the issues surrounding the design and delivery of dementia-friendly services in rural communities. The research question seeks to understand the barriers and drivers to the development of relevant, robust, reliable and accessible services that make a difference among older rural families affected by dementia. METHODS AND ANALYSIS: This mixed methods study recruits both families affected by dementia who reside within the Peak District National Park, Derbyshire, and their service providers. The study explores the expectations and experiences of rural dementia by adopting a three-part approach 1 : longitudinal ethnographic enquiry with up to 32 families affected by dementia (aged 70 years plus) who identify themselves as rural residents 2 ; ethnographic semistructured interviews and systematic observations of a range of statutory, third sector, private and local community initiatives that seek to support older people living with dementia 3 ; and geospatial visual mapping of the qualitative and quantitative data. The ethnographic data will be used to explore the ideas of belonging in a community, perceptions of place and identity to determine the factors that influence everyday decisions about living well with dementia and, for the providers, working in a rural community. The geospatial component of the study seeks to incorporate quantitative and qualitative data, such as types, locations and allocation of services to produce an interactive web-based map for local communities to determine the future design and delivery of services when considering dementia-friendly services. ETHICS AND DISSEMINATION: The study is approved by the Leeds and Humberside Health Research Authority 16/YH/0163. The study is also approved by other participating organisations as required by their own governance procedures. The study includes people with dementia and as such adheres to the ethical considerations when including people with dementia. A publicly available interactive visual map of the findings will be produced in relation to current services related to location and, by default, identify gaps in provision. Formal reports and dissemination activities will be undertaken in collaboration with the study advisory group members. STUDY PROGRESS: The recruitment began in September 2016. The data analysis commenced June 2017, using 59 provider interviews and 27 family participants. Data collection will be completed June 2018. NOTE ON TERMINOLOGY: Please note that the term 'families affected by dementia' is the preferred term of usage by the family members of the Scaling the Peaks Study Advisory Group. The group wish to emphasise that they consider this term to be more representative of their lives than the term living with dementia. TRIAL REGISTRATION NUMBER: NIHR IRAS 188103; Pre-results.

Correlation of Structural and Magnetic Properties in a Set of Mononuclear Lanthanide Complexes.

The electronic and magnetic properties of a set of mononuclear terbium(III) and dysprosium(III) complexes with two tetradentate 1-hydroxy-pyridin-2-one (1,2-HOPO) ligands are reported. Two primary coordination geometries are observed, depending on the length of the linker between the 1,2-HOPO donor moieties and the resulting arrangements of the linker. Fine details of the magnetic circular dichroism (MCD) spectra of the dysprosium(III) complexes illustrate differences in the splitting of the J multiplets and allow for a thorough ligand field analysis. High frequency electron paramagnetic resonance (HF-EPR) studies of the terbium(III) complexes give insight into the composition of the ground states. Ab initio calculations are utilized to rationalize the experimental results and further illustrate the effect of the structural features on the electronic and magnetic properties of the different complexes.

Spin Crossover in a Hexaamineiron(II) Complex: Experimental Confirmation of a Computational Prediction.

Single crystal structural analysis of [FeII (tame)2 ]Cl2 ⋅MeOH (tame=1,1,1-tris(aminomethyl)ethane) as a function of temperature reveals a smooth crossover between a high temperature high-spin octahedral d6 state and a low temperature low-spin ground state without change of the symmetry of the crystal structure. The temperature at which the high and low spin states are present in equal proportions is T1/2 =140 K. Single crystal, variable-temperature optical spectroscopy of [FeII (tame)2 ]Cl2 ⋅MeOH is consistent with this change in electronic ground state. These experimental results confirm the spin activity predicted for [FeII (tame)2 ]2+ during its de novo artificial evolution design as a spin-crossover complex [Chem. Inf. MODEL: 2015, 55, 1844], offering the first experimental validation of a functional transition-metal complex predicted by such in silico molecular design methods. Additional quantum chemical calculations offer, together with the crystal structure analysis, insight into the role of spin-passive structural components. A thermodynamic analysis based on an Ising-like mean field model (Slichter-Drickammer approximation) provides estimates of the enthalpy, entropy and cooperativity of the crossover between the high and low spin states.

Isomerism and reactivity of nickel(ii) acetylacetonate bis(thiosemicarbazone) complexes.

The complexation of nickel(ii) with acetylacetonate bis(thiosemicarbazone) N2S2 ligands with varying substituents has revealed that two isomers can exist independently in solution. These isomers differ according to the formation of either a 5,6,5-membered (symmetric) or a 4,7,5-membered (asymmetric) chelate ring arrangement. These two isomers have distinctly different properties. The symmetric complex (sym-[Ni(acacR)]) is unstable in the presence of air and slowly converts to the oxidised analogue sym-[Ni(acacRO)] with a carbonyl group installed at the apical C-atom. The mechanism of this O-atom transfer reaction is still unclear but kinetic and spectroelectrochemical experiments in addition to Density Functional Theory calculations have identified a single electron oxidised NiII-ligand radical complex as a key intermediate. By contrast the asymmetric complex, asym-[Ni(acacR)] is inert to ligand oxidation.

BonnMag: Computer program for ligand-field analysis of f n systems within the angular overlap model.

The program BonnMag has been developed to calculate the absorption spectra and temperature dependent magnetic susceptibilities of f n systems. The computations of the transition energies are performed within the angular overlap model. Using Judd-Ofelt theory BonnMag allows estimation of the relative absorption coefficients of the electronic transitions with reasonable accuracy. A description of the theoretical background of the implemented methods is given. Using Slater-Condon-Shortley parameters and spin-orbit coupling coefficients for free Ln3+ ions from ab initio calculations, the transition energies of all Ln3+ ions are calculated and compared to the results from CASSCF/NEV-PT2 calculations. Splitting due to the ligand field as well as transition energies of all Cs2 NaLnCl6 (except Gd and Pm) are calculated using parameters reported in the literature. Based on the comparison between theory and experiment, the potential and limitations of the program BonnMag are shown. © 2017 Wiley Periodicals, Inc.

Design of silk proteins with increased heme binding capacity and fabrication of silk-heme materials.

In our previous studies, heme was bound into honeybee silk to generate materials that could function as nitric oxide sensors or as recoverable heterogeneous biocatalysts. In this study, we sought to increase the heme-binding capacity of the silk protein by firstly redesigning the heme binding site to contain histidine as the coordinating residue and secondly, by adding multiple histidine residues within the core of the coiled coil core region of the modified silk protein. We used detergent and a protein denaturant to confirm the importance of the helical structure of the silk for heme coordination. Aqueous methanol treatment, which was used to stabilize the materials, transformed the low-spin, six-coordinate heme to a five-coordinate high-spin complex, thus providing a vacant site for ligand binding. The optimal aqueous methanol treatment time that simultaneously maintains the helical protein structure and stabilizes the silk material without substantial leaching of heme from the system was determined.

Effects of mutations in active site heme ligands on the spectroscopic and catalytic properties of SoxAX cytochromes.

By attaching a sulfur substrate to a conserved cysteine of the SoxYZ carrier protein SoxAX cytochromes initiate the reaction cycle of the Sox (sulfur oxidation) multienzyme complex, which is the major pathway for microbial reoxidation of sulfur compounds in the environment. Despite their important role in this process, the reaction mechanism of the SoxAX cytochromes has not been fully elucidated. Here we report the effects of several active site mutations on the spectroscopic and enzymatic properties of the type II SoxAX protein from Starkeya novella, which in addition to two heme groups also contains a Cu redox centre. All substituted proteins contained these redox centres except for His231Ala which was unable to bind Cu(II). Substitution of the SoxA active site heme cysteine ligand with histidine resulted in increased microheterogeneity around the SoxA heme as determined by CW-EPR, while a SnSoxAXC236A substituted protein revealed a completely new, nitrogenous SoxA heme ligand. The same novel ligand was present in SnSoxAXH231A CW-EPR spectra, the first time that a ligand switch of the SoxA heme involving a nearby amino acid has been demonstrated. Kinetically, SnSoxAXC236A and SnSoxAXC236H showed reduced turnover, and in assays containing SoxYZ these mutants retained only ~25% of the wildtype activity. Together, these data indicate that the Cu redox centre can mediate a low level of activity, and that a possible ligand switch can occur during catalysis. It also appears that the SoxA heme cysteine ligand (and possibly the low redox potential) is important for an efficient reaction with SnSoxYZ/thiosulfate.

Magnetic Interactions in a Series of Homodinuclear Lanthanide Complexes.

A series of seven isostructural homodinuclear lanthanide complexes are reported. The magnetic properties (ac and dc SQUID measurements) are discussed on the basis of the X-ray structural properties which show that the two lanthanide sites are structurally different. MCD spectroscopy of the dysprosium(III) and neodymium(III) complexes ([Dy(III)2(L)(OAc)4](+) and [Nd(III)2(L)(OAc)4](+)) allowed us to thoroughly analyze the ligand field, and high-frequency EPR spectroscopy of the gadolinium(III) species ([Gd(III)2(L)(OAc)4](+)) showed the importance of dipolar coupling in these systems. An extensive quantum-chemical analysis of the dysprosium(III) complex ([Dy(III)2(L)(OAc)4](+)), involving an ab initio (CASSCF) wave function, explicit spin-orbit coupling (RASSI-SO), and a ligand field analysis (Lines model and Stevens operators), is in full agreement with all experimental data (SQUID, HF-EPR, MCD) and specifically allowed us to accurately simulate the experimental χT versus T data, which therefore allowed us to establish a qualitative model for all relaxation pathways.