Family functioning differences across the deployment cycle in British Army families: the perceptions of wives and children

Introduction Military deployment can have an adverse effect on a soldier’s family, though little research has looked at these effects in a British sample. We investigated wives’ of UK serving soldiers perceptions of marital and family functioning, across three stages of the deployment cycle: currently deployed, post-deployment and pre-deployed, plus a non-military comparison group. Uniquely, young (aged 3.5 – 11 years) children’s perceptions of their family were also investigated, using the Parent-Child Alliance (PCA) coding scheme of drawings of the family. Materials and Methods Two hundred and twenty British military families of regular service personnel from the British Army’s Royal Armoured Corps (RAC), were sent survey packs distributed with a monthly welfare office newsletter. Wives were asked to complete a series of self-report items, and the youngest child in the family between the ages of 3.5 and 11 years was asked to draw a picture of their family. Complete data were available for 78 military families, and an additional 34 non-military families were recruited via opportunity sampling. Results Results indicated wives of currently deployed and recently returned personnel were less satisfied with their family and its communication, and children’s pictures indicated higher levels of dysfunctional PCA, whilst pre-deployed families responded similarly to non-military families. Marital satisfaction was similar across all groups except pre-deployed families who were significantly more satisfied. Non-military and pre-deployed families showed balanced family functioning, and currently and recently deployed families demonstrated poor family functioning. In comparison to non-military families, pre-deployed families showed a large ‘spike’ in the rigidity subscale of the FACES IV. Conclusion Wives’ perceptions of family functioning, but not marital satisfaction, differed between the deployment groups. The results from the coded children’s drawings correlated with the self-report measures from the wife/mother, indicating that children’s drawings could be a useful approach when working with younger children in this area. It is tentatively suggested that the differences across deployment stage on family functioning could be mediated not only by communication difficulties between deployed personnel and their families, but also by its effect on the children in the family. Larger-scale longitudinal research is needed to investigate this further

Is saltwater intrusion occurring from the Avon River into the shallow aquifer in Christchurch, New Zealand?

Introduction:Seawater intrusion (SI) is the landward movement of saltwater into fresh coastal aquifers. SI is a global issue intensified by climate change-induced sea-level rise. Tidal rivers are a source of saltwater that can render the adjacent shallow aquifer vulnerable to SI (Fig. 1). In this study, we investigated the potential for SI from the tidal Avon River into the adjacent unconfined aquifer in Christchurch. We add to previous work by Rutter1 that identified temperature fluctuations with tide within a number of shallow monitoring wells near the Avon River. Our study aims to identify whether solute transport is occurring from the river into the adjacent aquifer

Evaluation of an open access echocardiography service in the Netherlands: a mixed methods study of indications, outcomes, patient management and trends

Background: In our region (Eastern South Limburg, The Netherlands) an open access echocardiography service started in 2002. It was the first service of this kind in The Netherlands. Our study aims were: (1) to evaluate demand for the service, participation, indications, echocardiography outcomes, and management by the general practitioner (GP); (2) to analyse changes in indications and outcomes over the years. Methods: (1) Data from GP request forms, echocardiography reports and a retrospective GP questionnaire on management (response rate 83%) of 625 consecutive patients (Dec. 2002-March 2007) were analysed cross-sectionally. (2) For the analysis of changes over the years, data from GP request forms and echocardiography reports of the first and last 250 patients that visited the service between Dec. 2002 and Feb. 2008 (n = 1001) were compared. Results: The echocardiography service was used by 81% of the regional GPs. On average, a GP referred one patient per year to the service. Intended indications for the service were dyspnoea (32%), cardiac murmur (59%), and peripheral oedema (17%). Of the other indications (22%), one-third was for evaluation of suspected left ventricular hypertrophy (LVH). Expected outcomes were left ventricular dysfunction (LVD) (43%, predominantly diastolic) and valve disease (25%). We also found a high proportion of LVH (50%). Only 24% of all echocardiograms showed no relevant disease. The GP followed the cardiologist's advice to refer the patient for further evaluation in 71%. In recent patients, more echocardiography requests were done for 'cardiac murmur' and 'other' indications, but less for 'dyspnoea'. The proportions of patients with LVD, LVH and valve disease decreased and the proportion of patients with no relevant disease increased. The number of advices by the cardiologists increased. Conclusion: Overall, GPs used the open access echocardiography service efficiently (i. e. with a high chance of finding relevant pathology), but efficiency decreased slightly over the years. To meet the needs of the GPs, indications might be widened with 'suspicion LVH'. Further specification of the indications for open access echocardiography-by defining a stepwise diagnostic approach including ECG and (NT-pro)BNP-might improve the service

Development and Validation of Population Clusters for Integrating Health and Social Care: Protocol for a Mixed Methods Study in Multiple Long-Term Conditions (Cluster-Artificial Intelligence for Multiple Long-Term Conditions)

Background: Multiple long-term health conditions (multimorbidity) (MLTC-M) are increasingly prevalent and associated with high rates of morbidity, mortality, and health care expenditure. Strategies to address this have primarily focused on the biological aspects of disease, but MLTC-M also result from and are associated with additional psychosocial, economic, and environmental barriers. A shift toward more personalized, holistic, and integrated care could be effective. This could be made more efficient by identifying groups of populations based on their health and social needs. In turn, these will contribute to evidence-based solutions supporting delivery of interventions tailored to address the needs pertinent to each cluster. Evidence is needed on how to generate clusters based on health and social needs and quantify the impact of clusters on long-term health and costs. Objective: We intend to develop and validate population clusters that consider determinants of health and social care needs for people with MLTC-M using data-driven machine learning (ML) methods compared to expert-driven approaches within primary care national databases, followed by evaluation of cluster trajectories and their association with health outcomes and costs. Methods: The mixed methods program of work with parallel work streams include the following: (1) qualitative semistructured interview studies exploring patient, caregiver, and professional views on clinical and socioeconomic factors influencing experiences of living with or seeking care in MLTC-M; (2) modified Delphi with relevant stakeholders to generate variables on health and social (wider) determinants and to examine the feasibility of including these variables within existing primary care databases; and (3) cohort study with expert-driven segmentation, alongside data-driven algorithms. Outputs will be compared, clusters characterized, and trajectories over time examined to quantify associations with mortality, additional long-term conditions, worsening frailty, disease severity, and 10-year health and social care costs. Results: The study will commence in October 2021 and is expected to be completed by October 2023. Conclusions: By studying MLTC-M clusters, we will assess how more personalized care can be developed, how accurate costs can be provided, and how to better understand the personal and medical profiles and environment of individuals within each cluster. Integrated care that considers “whole persons” and their environment is essential in addressing the complex, diverse, and individual needs of people living with MLTC-M

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination