Autosomal recessive congenital ichthyosis due to novel CYP4F22 mutation presenting with a collodion membrane and ocular manifestations.

Autosomal recessive congenital ichthyoses (ARCI) are a range of genetic disorders of keratinization. The rare CYP4F22 gene mutation can present with or without collodion membrane at birth and leads to the development of mild ichthyosis phenotype. We report a case of a novel pathogenic CYP4F22 genetic mutation presenting with collodion membrane and ocular manifestations. Ocular manifestations have recently been reported in a patient with ARCI with known CYP4F22 mutation, which further supports a possible correlation between the CYP4F22 mutation and this distinct phenotype.

The Dimeglio Olecranon Method Is Reliable in Diverse, Contemporary Patients for Predicting Future Growth.

BACKGROUND: Growth assessment, which relies on a combination of radiographic and clinical markers, is an integral part of clinical decision-making in pediatric orthopaedics. The aim of this study is to evaluate the accuracy and reliability of the Diméglio skeletal age system using a modern cohort of pediatric patients. METHODS: A retrospective review was undertaken of all patients at a large tertiary pediatric hospital who had lateral forearm radiographs (before the age of 14 y for females and before 16 y for males). In addition, all of these patients had height measurements within 60 days of their forearm x-ray and a final height listed in their medical records. The x-rays were graded by 5 reviewers according to the Diméglio skeletal age system. Inter and intraobserver reliability was tested. RESULTS: One hundred forty-seven patients with complete radiographs and height data were evaluated by 5 observers ranging in experience from medical students to senior pediatric orthopaedic surgeons. The Diméglio system demonstrated excellent reliability across levels of training with an intraobserver correlation coefficient of 0.995 (95% CI, 0.991-0.997) and an interobserver correlation coefficient of 0.906 (95% CI, 0.857-0.943). When the Diméglio stage was paired with age and sex in a multivariable linear regression model predicting the percent of final height, the adjusted R2 was 78.7% (model P value <0.001), suggesting a strong relationship between the Diméglio stage (plus age and sex) and percent of final height. CONCLUSION: This unique approach to maturity assessment demonstrates that the Diméglio staging system can be used effectively in a modern, diverse patient population. LEVEL OF EVIDENCE: Level II; retrospective cohort study.

Flares in patients with systemic lupus erythematosus.

OBJECTIVE: SLE is characterized by relapses and remissions. We aimed to describe the frequency, type and time to flare in a cohort of SLE patients. METHODS: SLE patients with one or more 'A' or 'B' BILAG-2004 systems meeting flare criteria ('new' or 'worse' items) and requiring an increase in immunosuppression were recruited from nine UK centres and assessed at baseline and monthly for 9 months. Subsequent flares were defined as: severe (any 'A' irrespective of number of 'B' flares), moderate (two or more 'B' without any 'A' flares) and mild (one 'B'). RESULTS: Of the 100 patients, 94% were female, 61% White Caucasians, mean age (s.d.) was 40.7 years (12.7) and mean disease duration (s.d.) was 9.3 years (8.1). A total of 195 flares re-occurred in 76 patients over 781 monthly assessments (flare rate of 0.25/patient-month). There were 37 severe flares, 32 moderate flares and 126 mild flares. By 1 month, 22% had a mild/moderate/severe flare and 22% had a severe flare by 7 months. The median time to any 'A' or 'B' flare was 4 months. Severe/moderate flares tended to be in the system(s) affected at baseline, whereas mild flares could affect any system. CONCLUSION: . In a population with active SLE we observed an ongoing rate of flares from early in the follow-up period with moderate-severe flares being due to an inability to fully control the disease. This real-world population study demonstrates the limitations of current treatments and provides a useful reference population from which to inform future clinical trial design.

Screening for aspiration risk associated with dysphagia in acute stroke.

BACKGROUND: Stroke can affect people's ability to swallow, resulting in passage of some food and drink into the airway. This can cause choking, chest infection, malnutrition and dehydration, reduced rehabilitation, increased risk of anxiety and depression, longer hospital stay, increased likelihood of discharge to a care home, and increased risk of death. Early identification and management of disordered swallowing reduces risk of these difficulties. OBJECTIVES: Primary objective • To determine the diagnostic accuracy and the sensitivity and specificity of bedside screening tests for detecting risk of aspiration associated with dysphagia in people with acute stroke Secondary objectives • To assess the influence of the following sources of heterogeneity on the diagnostic accuracy of bedside screening tools for dysphagia - Patient demographics (e.g. age, gender) - Time post stroke that the study was conducted (from admission to 48 hours) to ensure only hyperacute and acute stroke swallow screening tools are identified - Definition of dysphagia used by the study - Level of training of nursing staff (both grade and training in the screening tool) - Low-quality studies identified from the methodological quality checklist - Type and threshold of index test - Type of reference test SEARCH METHODS: In June 2017 and December 2019, we searched CENTRAL, MEDLINE, Embase, CINAHL, and the Health Technology Assessment (HTA) database via the Centre for Reviews and Dissemination; the reference lists of included studies; and grey literature sources. We contacted experts in the field to identify any ongoing studies and those potentially missed by the search strategy. SELECTION CRITERIA: We included studies that were single-gate or two-gate studies comparing a bedside screening tool administered by nurses or other healthcare professionals (HCPs) with expert or instrumental assessment for detection of aspiration associated with dysphagia in adults with acute stroke admitted to hospital. DATA COLLECTION AND ANALYSIS: Two review authors independently screened each study using the eligibility criteria and then extracted data, including the sensitivity and specificity of each index test against the reference test. A third review author was available at each stage to settle disagreements. The methodological quality of each study was assessed using the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS-2) tool. We identified insufficient studies for each index test, so we performed no meta-analysis. Diagnostic accuracy data were presented as sensitivities and specificities for the index tests. MAIN RESULTS: Overall, we included 25 studies in the review, four of which we included as narratives (with no accuracy statistics reported). The included studies involved 3953 participants and 37 screening tests. Of these, 24 screening tests used water only, six used water and other consistencies, and seven used other methods. For index tests using water only, sensitivity and specificity ranged from 46% to 100% and from 43% to 100%, respectively; for those using water and other consistencies, sensitivity and specificity ranged from 75% to 100% and from 69% to 90%, respectively; and for those using other methods, sensitivity and specificity ranged from 29% to 100% and from 39% to 86%, respectively. Twenty screening tests used expert assessment or the Mann Assessment of Swallowing Ability (MASA) as the reference, six used fibreoptic endoscopic evaluation of swallowing (FEES), and 11 used videofluoroscopy (VF). Fifteen screening tools had an outcome of aspiration risk, 20 screening tools had an outcome of dysphagia, and two narrative papers did not report the outcome. Twenty-one screening tests were carried out by nurses, and 16 were carried out by other HCPs (not including speech and language therapists (SLTs)). We assessed a total of six studies as low risk across all four QUADAS-2 risk of bias domains, and we rated 15 studies as low concern across all three applicability domains. No single study demonstrated 100% sensitivity and specificity with low risk of bias for all domains. The best performing combined water swallow and instrumental tool was the Bedside Aspiration test (n = 50), the best performing water plus other consistencies tool was the Gugging Swallowing Screen (GUSS; n = 30), and the best water only swallow screening tool was the Toronto Bedside Swallowing Screening Test (TOR-BSST; n = 24). All tools demonstrated combined highest sensitivity and specificity and low risk of bias for all domains. However, clinicians should be cautious in their interpretation of these findings, as these tests are based on single studies with small sample sizes, which limits the estimates of reliability of screening tests. AUTHORS' CONCLUSIONS: We were unable to identify a single swallow screening tool with high and precisely estimated sensitivity and specificity based on at least one trial with low risk of bias. However, we were able to offer recommendations for further high-quality studies that are needed to improve the accuracy and clinical utility of bedside screening tools.

Oral care practices in stroke: findings from the UK and Australia.

AIMS: To examine current practice, perceptions of healthcare professionals and factors affecting provision for oral care post-stroke in the UK and Australia. BACKGROUND: Poor oral care has negative health consequences for people post-stroke. Little is known about oral care practice in hospital for people post-stroke and factors affecting provision in different countries. DESIGN: A cross-sectional survey. METHODS: Questionnaires were mailed to stroke specialist nurses in UK and Australian hospitals providing inpatient acute or rehabilitation care post-stroke. The survey was conducted between April and November 2019. Non-respondents were contacted up to five times. RESULTS: Completed questionnaires were received from 150/174 (86%) hospitals in the UK, and 120/162 (74%) in Australia. A total of 52% of UK hospitals and 30% of Australian hospitals reported having a general oral care protocol, with 53% of UK and only 13% of Australian hospitals reporting using oral care assessment tools. Of those using oral care assessment tools, 50% of UK and 38% of Australian hospitals used local hospital-specific tools. Oral care assessments were undertaken on admission in 73% of UK and 57% of Australian hospitals. Staff had received oral care training in the last year in 55% of UK and 30% of Australian hospitals. Inadequate training and education on oral care for pre-registration nurses were reported by 63% of UK and 53% of Australian respondents. CONCLUSION: Unacceptable variability exists in oral care practices in hospital stroke care settings. Oral care could be improved by increasing training, performing individual assessments on admission, and using standardised assessment tools and protocols to guide high quality care. The study highlights the need for incorporating staff training and the use of oral care standardised assessments and protocols in stroke care in order to improve patient outcomes.

The next generation of biopanning: next gen sequencing improves analysis of bacterial display libraries.

BACKGROUND: Bacterial surface display libraries are a popular tool for novel ligand discovery due to their ease of manipulation and rapid growth rates. These libraries typically express a scaffold protein embedded within the outer membrane with a short, surface-exposed peptide that is either terminal or is incorporated into an outer loop, and can therefore interact with and bind to substrates of interest. RESULTS: In this study, we employed a novel bacterial peptide display library which incorporates short 15-mer peptides on the surface of E. coli, co-expressed with the inducible red fluorescent protein DsRed in the cytosol, to investigate population diversity over two rounds of biopanning. The naive library was used in panning trials to select for binding affinity against 3D printing plastic coupons made from polylactic acid (PLA). Resulting libraries were then deep-sequenced using next generation sequencing (NGS) to investigate selection and diversity. CONCLUSIONS: We demonstrated enrichment for PLA binding versus a sapphire control surface, analyzed population composition, and compared sorting rounds using a binding assay and fluorescence microscopy. The capability to produce and describe display libraries through NGS across rounds of selection allows a deeper understanding of population dynamics that can be better directed towards peptide discovery.

An educational intervention to prevent overweight in pre-school years: a cluster randomised trial with a focus on disadvantaged families.

BACKGROUND: Early prevention is a promising strategy for reducing obesity in childhood, and Early Years settings are ideal venues for interventions. This work evaluated an educational intervention with the primary aim of preventing overweight and obesity in pre-school children. METHODS: A pragmatic, cluster randomised trial with a parallel, matched-pair design was undertaken. Interventions were targeted at both the cluster (Early Years' Centres, matched by geographical area) and individual participant level (families: mother and 2-year old child). At the cluster level, a staff training intervention used the educational resource Be Active, Eat Healthy. Policies and provision for healthy eating and physical activity were evaluated at baseline and 12-months. The intervention at participant level was the Healthy Heroes Activity Pack: delivered over 6 months by Centre staff to promote healthy eating and physical activity in a fun, interactive way. Child and parent height and weight were measured at four time-points over 2 years. The trial primary outcome was the change in BMI z-score of the child between ages 2 and 4 years. Secondary outcomes consisted of parent-reported measures administered at baseline and two-year follow-up. RESULTS: Five pairs of Early Years' Centres were recruited. Four pairs were analysed as one Centre withdrew (47 intervention families; 34 control families). At the cluster level, improvement in Centre policies and practices was similar for both groups (p = 0.830). At the participant level, the intervention group reduced their mean BMI z-score between age 2 and 4 years (p = 0.002; change difference 0.49; 95% CI 0.17 to 0.80) whereas the control group showed increasing BMI z-score throughout. Changes in parent-reported outcomes and parent BMI (p = 0.582) were similar in both groups. CONCLUSIONS: The Healthy Heroes educational resource deterred excess weight gain in pre-school children from poor socioeconomic areas. With training, Early Years' staff can implement the Healthy Heroes programme. TRIAL REGISTRATION: ISRCTN22620137 Registered 21st December 2016.

Living Bacteria-Nanoparticle Hybrids Mediated through Surface-Displayed Peptides.

In this study, we investigated the preparation of living bacteria-nanoparticle hybrids mediated by surface-displayed peptides. The assembly of metallic nanoparticles on living bacteria has been achieved under mild conditions utilizing metal-peptide interactions, whereas the viability of the bacterial cells was greatly preserved. Escherichia coli was engineered with inducible gene circuits to control the display of peptides with desired sequences. Several designed peptide sequences as well as known gold-binding peptides were expressed on the cell surface using enhanced circularly permuted outer membrane protein X (eCPX) scaffolds. Driven by metal-peptide affinity, "biofriendly" citrate-stabilized gold nanoparticles were self-assembled onto the surface of bacteria with displayed peptides, which required overcoming the repulsive force between negatively charged nanoparticles and negatively charged cells. The bacteria/Au nanoparticle hybrids were highly viable and maintained the ability to grow and divide, which is a crucial step toward the creation of living material systems. Further activity and preservation of the bacterial hybrid assembly was demonstrated. The method described herein enables the conjugation of bacterial surfaces with diverse metal-rich nanoparticles in an inducible, and therefore easily controlled, manner. The expressed peptide sequences can be easily modified to alter the binding affinity and specificity for a wide variety of materials to form on-demand, high-density living biohybrids.

Pilot Study Comparing Closed Versus Open Tracheal Suctioning in Postoperative Neonates and Infants With Complex Congenital Heart Disease.

OBJECTIVES: To determine the hemodynamic effect of tracheal suction method in the first 36 hours after high-risk infant heart surgery on the PICU and to compare open and closed suctioning techniques. DESIGN: Pilot randomized crossover study. SETTING: Single PICU in United Kingdom. PARTICIPANTS: Infants undergoing surgical palliation with Norwood Sano, modified Blalock-Taussig shunt, or pulmonary artery banding in the first 36 hours postoperatively. INTERVENTIONS: Infants were randomized to receive open or closed (in-line) tracheal suctioning either for their first or second study tracheal suction in the first 36 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Twenty-four infants were enrolled over 18 months, 11 after modified Blalock-Taussig shunt, seven after Norwood Sano, and six after pulmonary artery banding. Thirteen patients received the open suction method first followed by the closed suction method second, and 11 patients received the closed suction method first followed by the open suction method second in the first 36 hours after their surgery. There were statistically significant larger changes in heart rate (p = 0.002), systolic blood pressure (p = 0.022), diastolic blood pressure (p = 0.009), mean blood pressure (p = 0.007), and arterial saturation (p = 0.040) using the open suction method, compared with closed suctioning, although none were clinically significant (defined as requiring any intervention). CONCLUSIONS: There were no clinically significant differences between closed and open tracheal suction methods; however, there were statistically significant greater changes in some hemodynamic variables with open tracheal suctioning, suggesting that closed technique may be safer in children with more precarious physiology.

Unraveling the Roots of Selectivity of Peptide Affinity Reagents for Structurally Similar Ribosomal Inactivating Protein Derivatives.

Peptide capture agents have become increasingly useful tools for a variety of sensing applications due to their ease of discovery, stability, and robustness. Despite the ability to rapidly discover candidates through biopanning bacterial display libraries and easily mature them to Protein Catalyzed Capture (PCC) agents with even higher affinity and selectivity, an ongoing challenge and critical selection criteria is that the peptide candidates and final reagent be selective enough to replace antibodies, the gold-standard across immunoassay platforms. Here, we have discovered peptide affinity reagents against abrax, a derivative of abrin with reduced toxicity. Using on-cell Fluorescence Activated Cell Sorting (FACS) assays, we show that the peptides are highly selective for abrax over RiVax, a similar derivative of ricin originally designed as a vaccine, with significant structural homology to abrax. We rank the newly discovered peptides for strongest affinity and analyze three observed consensus sequences with varying affinity and specificity. The strongest (Tier 1) consensus was FWDTWF, which is highly aromatic and hydrophobic. To better understand the observed selectivity, we use the XPairIt peptide-protein docking protocol to analyze binding location predictions of the individual Tier 1 peptides and consensus on abrax and RiVax. The binding location profiles on the two proteins are quite distinct, which we determine is due to differences in pocket size, pocket environment (including hydrophobicity and electronegativity), and steric hindrance. This study provides a model system to show that peptide capture candidates can be quite selective for a structurally similar protein system, even without further maturation, and offers an in silico method of analysis for understanding binding and down-selecting candidates.

Phosphoketolase flux in Clostridium acetobutylicum during growth on L-arabinose.

Clostridium acetobutylicum's metabolic pathways have been studied for decades due to its metabolic diversity and industrial value, yet many details of its metabolism continue to emerge. The flux through the recently discovered pentose phosphoketolase pathway (PKP) in C. acetobutylicum has been determined for growth on xylose but transcriptional analysis indicated the pathway may have a greater contribution to arabinose metabolism. To elucidate the role of xylulose-5-phosphate/fructose-6-phosphate phosphoketolase (XFP), and the PKP in C. acetobutylicum, experimental and computational metabolic isotope analyses were performed under growth conditions of glucose or varying concentrations of xylose and arabinose. A positional bias in labelling between carbons 2 and 4 of butyrate was found and posited to be due to an enzyme isotope effect of the thiolase enzyme. A correction for the positional bias was applied, which resulted in reduction of residual error. Comparisons between model solutions with low residual error indicated flux through each of the two XFP reactions was variable, while the combined flux of the reactions remained relatively constant. PKP utilization increased with increasing xylose concentration and this trend was further pronounced during growth on arabinose. Mutation of the gene encoding XFP almost completely abolished flux through the PKP during growth on arabinose and resulted in decreased acetate/butyrate ratios. Greater flux through the PKP during growth on arabinose when compared with xylose indicated the pathway's primary role in C. acetobutylicum is arabinose metabolism.

A reference relative time-scale as an alternative to chronological age for cohorts with long follow-up.

BACKGROUND: Epidemiologists have debated the appropriate time-scale for cohort survival studies; chronological age or time-on-study being two such time-scales. Importantly, assessment of risk factors may depend on the choice of time-scale. Recently, chronological or attained age has gained support but a case can be made for a 'reference relative time-scale' as an alternative which circumvents difficulties that arise with this and other scales. The reference relative time of an individual participant is the integral of a reference population hazard function between time of entry and time of exit of the individual. The objective here is to describe the reference relative time-scale, illustrate its use, make comparison with attained age by simulation and explain its relationship to modern and traditional epidemiologic methods. RESULTS: A comparison was made between two models; a stratified Cox model with age as the time-scale versus an un-stratified Cox model using the reference relative time-scale. The illustrative comparison used a UK cohort of cotton workers, with differing ages at entry to the study, with accrual over a time period and with long follow-up. Additionally, exponential and Weibull models were fitted since the reference relative time-scale analysis need not be restricted to the Cox model. A simulation study showed that analysis using the reference relative time-scale and analysis using chronological age had very similar power to detect a significant risk factor and both were equally unbiased. Further, the analysis using the reference relative time-scale supported fully-parametric survival modelling and allowed percentile predictions and mortality curves to be constructed. CONCLUSIONS: The reference relative time-scale was a viable alternative to chronological age, led to simplification of the modelling process and possessed the defined features of a good time-scale as defined in reliability theory. The reference relative time-scale has several interpretations and provides a unifying concept that links contemporary approaches in survival and reliability analysis to the traditional epidemiologic methods of Poisson regression and standardised mortality ratios. The community of practitioners has not previously made this connection.

Light smoking at base-line predicts a higher mortality risk to women than to men; evidence from a cohort with long follow-up.

BACKGROUND: There is conflicting evidence as to whether smoking is more harmful to women than to men. The UK Cotton Workers' Cohort was recruited in the 1960s and contained a high proportion of men and women smokers who were well matched in terms of age, job and length of time in job. The cohort has been followed up for 42 years. METHODS: Mortality in the cohort was analysed using an individual relative survival method and Cox regression. Whether smoking, ascertained at baseline in the 1960s, was more hazardous to women than to men was examined by estimating the relative risk ratio women to men, smokers to never smoked, for light (1-14), medium (15-24), heavy (25+ cigarettes per day) and former smoking. RESULTS: For all-cause mortality relative risk ratios were 1.35 for light smoking at baseline (95% CI 1.07-1.70), 1.15 for medium smoking (95% CI 0.89-1.49) and 1.00 for heavy smoking (95% CI 0.63-1.61). Relative risk ratios for light smoking at baseline for circulatory system disease was 1.42 (95% CI 1.01 to 1.98) and for respiratory disease was 1.89 (95% CI 0.99 to 3.63). Heights of participants provided no explanation for the gender difference. CONCLUSIONS: Light smoking at baseline was shown to be significantly more hazardous to women than to men but the effect decreased as consumption increased indicating a dose response relationship. Heavy smoking was equally hazardous to both genders. This result may help explain the conflicting evidence seen elsewhere. However gender differences in smoking cessation may provide an alternative explanation.

A review of the design, manufacture, and outcomes of custom total joint replacement implants available in the United States.

Custom total joint replacement (TJA) implants, specifically designed and manufactured for each patient, have emerged as surgeons seek to improve functional outcomes of primary total joint replacement, as well as treat patients with complex primary deformities, bone defects, and revision surgeries. The purpose of this review is to present the various custom total hip and knee arthroplasty implants available in the United States for primary and revision cases, so that surgeons can understand the design considerations and manufacturing processes of custom implants, as well as their performance compared to standard implants.

Longitudinal association between lung function and health-related quality of life in cystic fibrosis.

BACKGROUND: Lung function is an important indicator of cystic fibrosis disease status and those with better forced expiratory volume in 1 s (FEV(1))% predicted have tended to report a better health-related quality of life (HRQoL) in cross-sectional studies. The relationship between lung function and HRQoL over time is unknown. This work assesses the natural progression of HRQoL reporting over many years and compares assessments across a whole decade and evaluates the relationship between lung function and HRQoL longitudinally. METHODS: Demographic (age, gender), clinical (FEV(1)% predicted, body mass index, diabetes, Burkholderia cepacia complex, intravenous access device and nutritional status) and HRQoL (Cystic Fibrosis Quality of Life Questionnaire) variables were obtained every 2 years over a 12-year period (seven time points from 1998 to 2010). RESULTS: HRQoL and lung function declined slowly over time and significant decade changes were observed for FEV(1)% predicted and the nine domains of the Cystic Fibrosis Quality of Life Questionnaire. The results of random coefficient modelling indicated that, at the population level, decreasing FEV(1)% predicted was associated with decreasing HRQoL after adjusting for confounding variables. However, the percentage of patients for whom a decrease in lung function was associated with a decrease in HRQoL differed according to the quality of life domain. CONCLUSIONS: HRQoL and FEV(1)% predicted decline slowly; nevertheless, a decrease in lung function predicted a decrease in HRQoL over time.

Photocurrent generation from surface assembled photosystem I on alkanethiol modified electrodes.

Photosystem I (PSI) is a key component of oxygenic photosynthetic electron transport because of its light-induced electron transfer to the soluble electron acceptor ferredoxin. This work demonstrates the incorporation of surface assembled cyanobacterial trimeric PSI complexes into a biohybrid system for light-driven current generation. Specifically, this work demonstrates the improved assembly of PSI via electrophoretic deposition, with controllable surface assembled PSI density, on different self-assembled alkanethiol monolayers. Using artificial electron donors and acceptors (Os(bpy)(2)Cl(2) and methyl viologen) we demonstrate photocurrent generation from a single PSI layer, which remains photoactive for at least three hours of intermittent illumination. Photoelectrochemical comparison of the biohybrid systems assembled from different alkanethiols (hexanethiol, aminohexanethiol, mercaptohexanol, and mercaptohexanoic acid) reveals that the PSI generated photocurrent is enhanced by almost 5 times on negatively charged SAM surfaces as compared to positively charged surfaces. These results are discussed in light of how PSI is oriented upon electrodeposition on a SAM.

Football metaphor and mental well-being: an evaluation of the It's a Goal! programme.

BACKGROUND: The It's a Goal! programme utilises football metaphor and football venues as a means to frame and deliver a non-clinical, group-based therapeutic intervention, targeting men with mental health needs. A pilot in the North West of England was hosted by seven professional football clubs in partnership with local Primary Care Trusts. AIMS: To evaluate the impact of the intervention and to identify the benefits and key components of the approach from the perspective of participants. METHOD: Analysis of impact utilised before and after well-being scores measured on a modified version of the Warwick-Edinburgh Mental Well-being Scale. Focus groups provided additional qualitative data that were analysed thematically. RESULTS: Findings suggest that It's a Goal! had a significant impact upon participant's well-being. In addition, participants reported a range of positive benefits especially in relation to confidence, self-esteem and developing better coping mechanisms. Participants related these benefits to a number of key components, not least the therapeutic value of football metaphor, the focus on goal-setting and the mutual support developed within the groups. CONCLUSIONS: Using football metaphor to deliver a group therapeutic programme aimed at men appears to be an effective means of facilitating mental health benefits.

Ways of coping and survival in Cystic Fibrosis: a 20-year longitudinal study.

BACKGROUND: The relationship between ways of coping and health outcomes has been a focus of interest for decades. There is increasing recognition that positive psychological functioning can influence health outcomes beneficially. This work investigated the role of coping in predicting survival in CF. METHODS: A longitudinal observational cohort study with a 20-year follow-up period was undertaken. At entry to the study, demographic and clinical variables were recorded, and ways of coping were assessed using the Cystic Fibrosis Coping Scale which measures four distinct ways of coping: optimism, hopefulness, distraction and avoidance. Survival outcome was measured as time in days from the date of recruitment to exit from the study, where exit was either death, loss to follow-up or the end of the follow-up period. RESULTS: Survival time was modelled using Cox's proportional hazards model. At baseline, 116 people with CF were recruited. By the census date, 54 people had died (14 men had died during 248,565 person-days of observation and 40 women had died during 358,372 person-days of observation). Optimism was the only way of coping that showed any beneficial effect on survival (RR=0.984, p=0.040) after adjustments for age, gender, ppFEV1 and the three other coping variables measured at baseline. CONCLUSION: This work suggests that optimistic coping serves as a prognostic measure of survival in CF beyond key clinical and demographic variables. Ways of coping are modifiable, providing a target for clinical intervention; to improve quality of life and clinical outcomes and potentially increase longevity.

Structural racism through Sundown towns and its relationship to COVID-19 local risk and racial and ethnic diversity.

"Sundown towns" across the US prevented racial and ethnic minorities from living and working within their borders as they forced minorities to leave these towns after sunset. The objective of this study was to explore the relationship between sundown town status, COVID-19 local risk index and racial and ethnic diversity. A multi-level hierarchical model was used to examine the effect of historical segregation through sundown towns status on present day COVID-19 local risk index and city-level diversity. Over 2,400 Sundown towns were cataloged across the United States, with the greatest density in the Midwest. Sundown towns, which historically excluded racial and ethnic minorities, had significantly less city-level diversity and lower COVID-19 local risk index compared to non-Sundown towns. Findings show that Sundown towns perpetuate residual segregation which continues to impact current inequities in COVID-19 risk among racial and ethnic minorities at the neighborhood level. We recommend that public health officials for pandemic preparedness should devote greater resources to these historically segregated racial and ethnic minority areas because of the historic structural racism that has placed these places at higher risk.

Identification of Microorganisms that Bind Specifically to Target Materials of Interest Using a Magnetophoretic Microfluidic Platform.

Discovery of microorganisms and their relevant surface peptides that specifically bind to target materials of interest can be achieved through iterative biopanning-based screening of cellular libraries having high diversity. Recently, microfluidics-based biopanning methods have been developed and exploited to overcome the limitations of conventional methods where controlling the shear stress applied to remove cells that do not bind or only weakly bind to target surfaces is difficult and the overall experimental procedure is labor-intensive. Despite the advantages of such microfluidic methods and successful demonstration of their utility, these methods still require several rounds of iterative biopanning. In this work, a magnetophoretic microfluidic biopanning platform was developed to isolate microorganisms that bind to target materials of interest, which is gold in this case. To achieve this, gold-coated magnetic nanobeads, which only attached to microorganisms that exhibit high affinity to gold, were used. The platform was first utilized to screen a bacterial peptide display library, where only the cells with surface peptides that specifically bind to gold could be isolated by the high-gradient magnetic field generated within the microchannel, resulting in enrichment and isolation of many isolates with high affinity and high specificity toward gold even after only a single round of separation. The amino acid profile of the resulting isolates was analyzed to provide a better understanding of the distinctive attributes of peptides that contribute to their specific material-binding capabilities. Next, the microfluidic system was utilized to screen soil microbes, a rich source of extremely diverse microorganisms, successfully isolating many naturally occurring microorganisms that show strong and specific binding to gold. The results show that the developed microfluidic platform is a powerful screening tool for identifying microorganisms that specifically bind to a target material surface of interest, which can greatly accelerate the development of new peptide-driven biological materials and hybrid organic-inorganic materials.