Diagnostic evaluation of upper tract urothelial carcinoma: can we safely omit diagnostic ureteroscopy?

OBJECTIVE: To identify clinicopathological or radiological factors that may predict a diagnosis of upper urinary tract urothelial cell carcinoma (UTUC) to inform which patients can proceed directly to radical nephroureterectomy (RNU) without the delay for diagnostic ureteroscopy (URS). PATIENTS AND METHODS: All consecutive patients investigated for suspected UTUC in a high-volume UK centre between 2011 and 2017 were identified through retrospective analysis of surgical logbooks and a prospectively maintained pathology database. Details on clinical presentation, radiological findings, and URS/RNU histopathology results were evaluated. Multivariate regression analysis was performed to evaluate predictors of a final diagnosis of UTUC. RESULTS: In all, 260 patients were investigated, of whom 230 (89.2%) underwent URS. RNU was performed in 131 patients (50.4%), of whom 25 (9.6%) proceeded directly without URS - all of whom had a final histopathological diagnosis of UTUC - and 15 (11.5%) underwent RNU after URS despite no conclusive histopathological confirmation of UTUC. Major surgery was avoided in 77 patients (33.5%) where a benign or alternative diagnosis was made on URS, and 14 patients (6.1%) underwent nephron-sparing surgery. Overall, 178 patients (68.5%) had a final diagnosis of UTUC confirmed on URS/RNU histopathology. On multivariate logistic regression analysis, a presenting complaint of visible haematuria (hazard ratio [HR] 5.17, confidence interval [CI] 1.91-14.0; P = 0.001), a solid lesion reported on imaging (HR 37.8, CI = 11.7-122.1; P < 0.001) and a history of smoking (HR 3.07, CI 1.35-6.97; P = 0.007), were predictive of a final diagnosis of UTUC. From this cohort, 51 (96.2%) of 53 smokers who presented with visible haematuria and who had a solid lesion on computed tomography urogram had UTUC on final histopathology. CONCLUSION: We identified specific factors which may assist clinicians in selecting which patients may reliably proceed to RNU without the delay of diagnostic URS. These findings may inform a prospective multicentre analysis including additional variables such as urinary cytology.

Prehospital early warning scores for adults with suspected sepsis: retrospective diagnostic cohort study.

BACKGROUND: Ambulance services need to identify and prioritise patients with sepsis for early hospital assessment. We aimed to determine the accuracy of early warning scores alongside paramedic diagnostic impression to identify sepsis that required urgent treatment. METHODS: We undertook a retrospective diagnostic cohort study involving adult emergency medical cases transported to Sheffield Teaching Hospitals ED by Yorkshire Ambulance Service in 2019. We used routine ambulance service data to calculate 21 early warning scores and categorise paramedic diagnostic impressions as sepsis, infection, non-specific presentation or other presentation. We linked cases to hospital records and identified those meeting the sepsis-3 definition who received urgent hospital treatment for sepsis (reference standard). Analysis determined the accuracy of strategies that combined early warning scores at varying thresholds for positivity with paramedic diagnostic impression. RESULTS: We linked 12 870/24 955 (51.6%) cases and identified 348/12 870 (2.7%) with a positive reference standard. None of the strategies provided sensitivity greater than 0.80 with positive predictive value greater than 0.15. The area under the receiver operating characteristic curve for the National Early Warning Score, version 2 (NEWS2) applied to patients with a diagnostic impression of sepsis or infection was 0.756 (95% CI 0.729, 0.783). No other early warning score provided clearly superior accuracy to NEWS2. Paramedic impression of sepsis or infection had sensitivity of 0.572 (0.519, 0.623) and positive predictive value of 0.156 (0.137, 0.176). NEWS2 thresholds of >4, >6 and >8 applied to patients with a diagnostic impression of sepsis or infection, respectively, provided sensitivities and positive predictive values of 0.522 (0.469, 0.574) and 0.216 (0.189, 0.245), 0.447 (0.395, 0.499) and 0.274 (0.239, 0.313), and 0.314 (0.268, 0.365) and 0.333 (0.284, 0.386). CONCLUSION: No strategy is ideal but using NEWS2 alongside paramedic diagnostic impression of infection or sepsis could identify one-third to half of sepsis cases without prioritising unmanageable numbers. No other score provided clearly superior accuracy to NEWS2. TRIAL REGISTRATION NUMBER: researchregistry5268, https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/5de7bbd97ca5b50015041c33/.

Modelling soil salinity effects on salt water uptake and crop growth using a modified denitrification-decomposition model: A phytoremediation approach.

Soil salinization is a widespread problem affecting global food production. Phytoremediation is emerging as a viable and cost-effective technology to reclaim salt-affected soil. However, its efficiency is not clear due to the uncertainty of plant responses in saline soils. The main objective of this paper is to propose a phytoremediation dynamic model (PDM) for salt-affected soil within the process-based biogeochemical denitrification-decomposition (DNDC) model. The PDM represents two salinity processes of phytoremediation: plant salt uptake and salt-affected biomass growth. The salt-soil-plant interaction is simulated as a coupled mass balance equation of water and salt plant uptake. The salt extraction ability by plant is a combination of salt uptake efficiency (F) and transpiration rate. For water filled pore space (WFPS), the statistical measures RMSE, MAE, and R2 during the calibration period are 2.57, 2.14, and 0.49, and they are 2.67, 2.34, and 0.56 during the validation period, respectively. For soil salinity, RMSE, MAE, and R2 during the calibration period are 0.02, 0.02, and 0.92, and 0.06, 0.04, and 0.68 during the validation period, respectively, which are reasonably good for further scenario analysis. Over the four years, cumulative salt uptake varied based on weather conditions. At the optimal salt uptake efficiency (F = 20), cumulative salt uptake from soil was 16-90% for alfalfa, 11-70% for barley, and 10-80% for spring wheat. While at the lowest salt uptake efficiency (F = 40), cumulative salt uptake was nearly zero for all crops. Although barley has the highest peak transpiration flux, alfalfa and spring wheat have greater cumulative salt uptake because their peak transpiration fluxes occurred more frequently than in barley. For salt-tolerant crops biomass growth depends on their threshold soil salinity which determines their ability to take up salt without affecting biomass growth. In order to phytoremediate salt-affected soil, salt-tolerant crops having longer duration of crop physiological stages should be used, but their phytoremediation effectiveness will depend on weather conditions and the soil environment.

From the Good Life to Good Living: A Longitudinal Study Investigating the Relationship Between Good-Life Coherence and Motivation, Goal Progress and Subjective Well-Being.

Although considerable research has examined the traits and features involved in living a good life (Baumeister et al. in J Posit Psychol 8(6):505-516, 2013; Ryan et al. in Self-determination theory: Basic psychological needs in motivation, development, and wellness, Guilford Press, 2006; Wong in Can Psychol/Psychol Can 52(2):69-81, 2011), little research has examined personal philosophies of the good life and the motivational outcomes associated with these views. Through a prospective longitudinal study across one academic year, we examined whether perceiving oneself to be living coherently with personal conceptions of the good life was associated with greater autonomous goal motivation and, subsequently, goal progress and greater subjective well-being (SWB) over time. We hypothesize that perceiving oneself as living coherently in terms of one's own philosophy of flourishing relates to greater volition, goal progress and happiness. Our results suggest that when individuals assess themselves as following their own philosophy of the good life, they tend to experience greater autonomous motivation, goal progress and SWB. Implications for personality coherence and Self-Determination Theory are discussed.

Comparison between thermophysical and tribological properties of two engine lubricant additives: electrochemically exfoliated graphene and molybdenum disulfide nanoplatelets.

Recently graphene and other 2D materials were suggested as nano additives to enhance the performance of nanolubricants and reducing friction and wear-related failures in moving mechanical parts. Nevertheless, to our knowledge there are no previous studies on electrochemical exfoliated nanomaterials as lubricant additives. In this work, engine oil-based nanolubricants were developed via two-steps method using two different 2D nanomaterials: a carbon-based nano additive, graphene nanoplatelets (GNP) and a sulphide nanomaterial, molybdenum disulfide (MoS2) nanoplatelets (MSNP). The influence of these nano additives on the thermophysical properties of the nanolubricants, such as viscosity index, density and wettability, was investigated. The unique features of the electrochemical exfoliated GNP and MSNP allow the formulation of nanolubricant with unusual thermophysical properties. Both the viscosity and density of the nanolubricants decreased by increasing the nanoplatelets loading. The effect of the nano additives loading and temperature on the tribological properties of nanolubricants was investigated using two different test configurations: reciprocating ball-on-plate and rotational ball-on-three-pins. The tribological specimens were analysed by scanning electron microscopy (SEM) and 3D profiler in order to evaluate the wear. The results showed significant improvement in the antifriction and anti-wear properties, for the 2D-materials-based nanolubricants as compared with the engine oil, using different contact conditions. For the reciprocal friction tests, maximum friction and worn area reductions of 20% and 22% were achieved for the concentrations of 0.10 wt% and 0.20 wt% GNP, respectively. Besides, the best anti-wear performance was found for the nanolubricant containing 0.05 wt% MSNP in rotational configuration test, with reductions of 42% and 60% in the scar width and depth, respectively, with respect to the engine oil.

Assessing fidelity of a community based psychosocial intervention for people with mild dementia within a large randomised controlled trial.

BACKGROUND: Understanding intervention delivery as intended, particularly in complex interventions, should be underpinned by good quality fidelity assessment. We present the findings from a fidelity assessment embedded as part of a trial of a complex community-based psychosocial intervention, Journeying through Dementia (JtD). The intervention was designed to equip individuals with the knowledge and skills to successfully self-manage, maintain independence, and live well with dementia and involves both group and individual sessions. The methodological challenges of developing a conceptual framework for fidelity assessment and creating and applying purposely designed measures derived from this framework are discussed to inform future studies. METHODS: A conceptual fidelity framework was created out of core components of the intervention (including the intervention manual and training for delivery), associated trial protocols and pre-defined fidelity standards and criteria against which intervention delivery and receipt could be measured. Fidelity data collection tools were designed and piloted for reliability and usability. Data collection in four selected sites (fidelity sites) was via non-participatory observations of the group aspect of the intervention, attendance registers and interventionist (facilitator and supervisor) self-report. RESULTS: Interventionists from all four fidelity sites attended intervention training. The majority of group participants at the four sites (71%) received the therapeutic dose of 10 out of 16 sessions. Weekly group meeting attendance (including at 'out of venue' sessions) was excellent at 80%. Additionally, all but one individual session was attended by the participants who completed the intervention. It proved feasible to create tools derived from the fidelity framework to assess in-venue group aspects of this complex intervention. Results of fidelity assessment of the observed groups were good with substantial inter-rater reliability between researchers KAPPA 0.68 95% CI (0.58-0.78). Self-report by interventionists concurred with researcher assessments. CONCLUSIONS: There was good fidelity to training and delivery of the group aspect of the intervention at four sites. However, the methodological challenges of assessing all aspects of this complex intervention could not be overcome due to practicalities, assessment methods and ethical considerations. Questions remain regarding how we can assess fidelity in community-based complex interventions without impacting upon intervention or trial delivery. TRIAL REGISTRATION: ISRCTN17993825 .

Prognostic accuracy of emergency department triage tools for adults with suspected COVID-19: the PRIEST observational cohort study.

BACKGROUND: The WHO and National Institute for Health and Care Excellence recommend various triage tools to assist decision-making for patients with suspected COVID-19. We aimed to compare the accuracy of triage tools for predicting severe illness in adults presenting to the ED with suspected COVID-19. METHODS: We undertook a mixed prospective and retrospective observational cohort study in 70 EDs across the UK. We collected data from people attending with suspected COVID-19 and used presenting data to determine the results of assessment with the WHO algorithm, National Early Warning Score version 2 (NEWS2), CURB-65, CRB-65, Pandemic Modified Early Warning Score (PMEWS) and the swine flu adult hospital pathway (SFAHP). We used 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome. RESULTS: We analysed data from 20 891 adults, of whom 4611 (22.1%) died or received organ support (primary outcome), with 2058 (9.9%) receiving organ support and 2553 (12.2%) dying without organ support (secondary outcomes). C-statistics for the primary outcome were: CURB-65 0.75; CRB-65 0.70; PMEWS 0.77; NEWS2 (score) 0.77; NEWS2 (rule) 0.69; SFAHP (6-point rule) 0.70; SFAHP (7-point rule) 0.68; WHO algorithm 0.61. All triage tools showed worse prediction for receipt of organ support and better prediction for death without organ support. At the recommended threshold, PMEWS and the WHO criteria showed good sensitivity (0.97 and 0.95, respectively) at the expense of specificity (0.30 and 0.27, respectively). The NEWS2 score showed similar sensitivity (0.96) and specificity (0.28) when a lower threshold than recommended was used. CONCLUSION: CURB-65, PMEWS and the NEWS2 score provide good but not excellent prediction for adverse outcome in suspected COVID-19, and predicted death without organ support better than receipt of organ support. PMEWS, the WHO criteria and NEWS2 (using a lower threshold than usually recommended) provide good sensitivity at the expense of specificity. TRIAL REGISTRATION NUMBER: ISRCTN56149622.

Post-exertion oxygen saturation as a prognostic factor for adverse outcome in patients attending the emergency department with suspected COVID-19: a substudy of the PRIEST observational cohort study.

BACKGROUND: Measurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19. METHODS: We undertook a substudy of an observational cohort study across 70 emergency departments during the first wave of the COVID-19 pandemic in the UK. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis. We constructed receiver-operating characteristic curves, calculated diagnostic parameters, and developed a multivariable model for predicting adverse outcome. RESULTS: We analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% CI 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were, respectively, 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019). CONCLUSIONS: Post-exertion oxygen saturation provides modest prognostic information in the assessment of selected patients attending the emergency department with suspected COVID-19. TRIAL REGISTRATION NUMBER: ISRCTN Registry (ISRCTN56149622) http://www.isrctn.com/ISRCTN28342533.

Modeling the effect of salt-affected soil on water balance fluxes and nitrous oxide emission using modified DNDC.

Soil salinity restricts plant growth, affects soil water balance and nitrous oxide (N2O) fluxes and can contaminate surface and groundwater. In this study, the Denitrification Decomposition (DNDC) model was modified to couple salt and water balance equations (SALT-DNDC) to investigate the effect of salinity on water balance and N2O fluxes. The model was examined against four growing seasons (2008-11) of observed data from Lethbridge, Alberta, Canada. Then, the model was used to simulate water filled pore space (WFPS), salt concentration and the N2O flux from agricultural soils. The results show that the effects of salinity on WFPS vary in different soil layers. Within shallow soil layers (<20 cm from soil surface) the salt concentration does not affect the average WFPS when initial salt concentrations range from 5 to 20 dS/m. However, in deeper soil layers (>20 cm from soil surface), when the initial salt concentration ranges from 5 to 20 dS/m it could indirectly affect the average WFPS due to changes of osmotic potential and transpiration. When AW is greater than 40%, the average growing season N2O emissions increase to a range of 0.6-1.0 g-N/ha/d at initial salt concentrations (5-20 dS/m) from a range of 0.5-0.7 g-N/ha/d when the salt concentrations is 0 dS/m. The newly developed SALT-DNDC model provides a unique tool to help investigate interactive effects among salt, soil, water, vegetation, and weather conditions on N2O fluxes.

The Therapeutic Engagement Questionnaire (TEQ): a service user-focused mental health nursing outcome metric.

BACKGROUND: Therapeutic engagement (TE) has been described as the crux of mental health nursing but despite its perceived importance, to date, there is no measurement tool that captures it. As a result, there is no way of determining the contribution of mental health nursing interaction to service user recovery, in acute inpatient mental health settings or the wider care quality agenda. METHODS: To develop and validate a TE measurement tool in partnership with Service Users (SUs) and Registered Mental Health Nurses (RMHNs). The TEQ was developed in 3 stages: 1) item generation (and pre-testing), 2) item reduction using Principal Component Analysis (PCA), and 3) validation across Mental Health Trusts in England. RESULTS: The final questionnaire has two versions, (SU and RMHN version), each scored within two contexts (1-1 SU-RMHN interactions and overall environment and atmosphere of the ward) and includes 20 items with two sub-scales (care interactions and care delivery). Psychometric evaluation of the TEQ shows high inter-scale correlations (0.66-0.95 SU; 0.57-0.90 RMHN), sound sub-scale internal consistency (> 0.95), concurrent validity (> 0.60) and adequate score variability for both versions of the TEQ. In summary, the TEQ behaves well as a measurement tool. CONCLUSIONS: The TEQ can determine the collaborative and empathic nature of RMHN-SU interactions, capture if SUs are treated with dignity and respect and recognise that the principles of the recovery approach are being respected. The TEQ can also provide robust monitoring of nursing activity, offer opportunity for transparency of activity, feed into healthcare organizations' key performance indicators and provide reassurance about the nature and quality of nurses' work.

Sticky swinging arm dynamics: studies of an acyl carrier protein domain from the mycolactone polyketide synthase.

Type I modular polyketide synthases (PKSs) produce polyketide natural products by passing a growing acyl substrate chain between a series of enzyme domains housed within a gigantic multifunctional polypeptide assembly. Throughout each round of chain extension and modification reactions, the substrate stays covalently linked to an acyl carrier protein (ACP) domain. In the present study we report on the solution structure and dynamics of an ACP domain excised from MLSA2, module 9 of the PKS system that constructs the macrolactone ring of the toxin mycolactone, cause of the tropical disease Buruli ulcer. After modification of apo ACP with 4'-phosphopantetheine (Ppant) to create the holo form, (15)N nuclear spin relaxation and paramagnetic relaxation enhancement (PRE) experiments suggest that the prosthetic group swings freely. The minimal chemical shift perturbations displayed by Ppant-attached C3 and C4 acyl chains imply that these substrate-mimics remain exposed to solvent at the end of a flexible Ppant arm. By contrast, hexanoyl and octanoyl chains yield much larger chemical shift perturbations, indicating that they interact with the surface of the domain. The solution structure of octanoyl-ACP shows the Ppant arm bending to allow the acyl chain to nestle into a nonpolar pocket, whereas the prosthetic group itself remains largely solvent exposed. Although the highly reduced octanoyl group is not a natural substrate for the ACP from MLSA2, similar presentation modes would permit partner enzyme domains to recognize an acyl group while it is bound to the surface of its carrier protein, allowing simultaneous interactions with both the substrate and the ACP.

Service user involvement in the coproduction of a mental health nursing metric: The Therapeutic Engagement Questionnaire.

Service users' involvement in mental health service research is increasingly acknowledged as important, yet, whilst involving users of mental health services as research participants is commonplace, seeking out their experience and indeed their "expertise" to facilitate the development of tools to be used within mental health services is in its infancy. This article describes the involvement and views of service users in the development of a nursing metric-the Therapeutic Engagement Questionnaire. It presents their role in the three stages of development: generation, statement reduction and authentication.

Surgical Management and Outcome of Renal Cell Carcinoma with Inferior Vena Cava Tumor Thrombus.

INTRODUCTION: The authors of this paper assessed the surgical management and outcome of renal cancers when tumor thrombus extended into the inferior vena cava (IVC). METHODS: From 2000 to 2015, 46 radical nephrectomies were performed on patients with tumor thrombus in the IVC. The mean age of the patients was 60 ± 11 years. Radical nephrectomy and thrombectomies were performed in a single session. There were 18 level-IV, 23 level-III, and 5 level-II tumor thrombi. The operations were performed using cardiopulmonary bypass in 14 patients, while deep hypothermic cardiac arrest was carried out in 4 cases. RESULTS: The mean size of the tumors was 9.4 ± 3.5 cm. Histology showed the tumor stages to be pT3b in 21cases, pT3c in 22, and pT4 in 3 patients. The mean follow-up period of the patients was 3.6 ± 3.0 years. During the follow-up period, local recurrence was observed in 7 patients, while distant metastases occurred in 8 cases. The median time to progression was 37 ± 27 months. The 5-year overall survival was 43.7%. CONCLUSIONS: Radical nephrectomy and thrombectomy provided reasonable long-term survival for patients with renal cancer and IVC thrombus. However, tumor progression was detected in 41.6%. The presence of tumor thrombus had a negative effect on tumor progression and survival.

Nitrous Oxide Emitted from Soil Receiving Anaerobically Digested Solid Cattle Manure.

Limited information is available about soil nitrous oxide (NO) fluxes, NO emission factors (EFs), and yield-scaled NO emissions for biogas residues used to fertilize crops in semiarid regions. To address this knowledge gap, a 4-yr field experiment was conducted in a semiarid climate to determine growing season NO fluxes from soil receiving (i) anaerobically digested solid beef cattle manure (digestate), (ii) separated solids from the digestate (separated solids), and (iii) undigested solid beef cattle manure (cattle manure) applied to target one and two times the recommended rates (200 and 400 kg total N ha) for barley ( L.) forage, assuming 50% of N was annually plant available. Nitrous oxide fluxes were determined using vented static chambers. Over the four growing seasons, 95, 80, and 81% of the NO flux occurred within 36 d of applying digestate, separated solids, and cattle manure, respectively. The cumulative NO emissions with digestate were 4.7 and 4.1 times the values of the separated solids and cattle manure, respectively. The digestate NO EF was 13.6 and 10.6 times the values of the separated solids and cattle manure, respectively, but the NO EF based on applied mineral N was similar for all amendments. The yield-scaled NO emissions with digestate were 4.3 and 3.6 times the values of the separated solids and cattle manure, respectively. In the semiarid region of southern Alberta, liquid biogas residues have a higher risk for NO emissions than both the separated solid fraction of the biogas residues and undigested cattle manure.

Evolution and oncological outcomes of a contemporary radical prostatectomy practice in a UK regional tertiary referral centre.

OBJECTIVE: To investigate the clinical and pathological trends, over a 10-year period, in robot-assisted laparoscopic prostatectomy (RALP) in a UK regional tertiary referral centre. PATIENTS AND METHODS: In all, 1 500 consecutive patients underwent RALP between October 2005 and January 2015. Prospective data were collected on clinicopathological details at presentation as well as surgical outcomes and compared over time. RESULTS: The median (range) age of patients throughout the period was 62 (35-78) years. The proportion of preoperative high-grade cases (Gleason score 8-10) rose from 4.6% in 2005-2008 to 18.2% in 2013-2015 (P < 0.001). In the same periods the proportion of clinical stage T3 cases operated on rose from 2.4% to 11.4% (P < 0.001). The median prostate-specific antigen (PSA) level at diagnosis did not alter significantly. Overall, 11.6% of men in 2005-2008 were classified preoperatively as high-risk by National Institute for Health and Care Excellence criteria, compared with 33.6% in 2013-2015 (P < 0.001). The corresponding proportions for low-risk cases were 48.6% and 17.3%, respectively. Final surgical pathology showed an increase in tumour stage, Gleason grade, and nodal status over time. The proportion of pT3 cases rose from 43.2% in 2005-2008 to 55.5% in 2013-2015 (P < 0.001), Gleason score 9-10 tumours increased from 1.8% to 9.1% (P < 0.001) and positive nodal status increased from 1.6% to 12.9% (P < 0.001) between the same periods. Despite this, positive surgical margin rates showed a downward trend in all pT groups across the different eras (P = 0.72). CONCLUSION: This study suggests that the patient profile for RALP in our unit is changing, with increasing proportions of higher stage and more advanced disease being referred and operated on. However, surgical margin outcomes have remained good.

Test-Retest reliability and measurement error of the uncontrolled manifold analysis: A step towards the clinical translation.

The uncontrolled manifold (UCM) analysis has gained broad application in biomechanics and neuroscience for investigating the structure of motor variability in functional tasks. The UCM utilizes inter-trial analysis to partition the variance of elemental variables (e.g., finger forces, joint angles) that affect (VORT) and do not affect (VUCM) a performance variable (e.g., total force, end-effector position). However, to facilitate the translation of UCM into clinical settings, it is crucial to demonstrate the reliability of UCM estimates: VORT, VUCM, and their normalized difference, ΔV. This study aimed to determine the test-retest reliability using the intraclass correlation coefficient (ICC3,K), Bland-Altman plots, the standard error of measurement (SEM), and the minimal detectable change (MDC) of UCM estimate. Fifteen healthy individuals (24.8 ± 1.2 yrs old) performed a finger coordination task, with sessions separated by one hour, one day, and one week. Excellent reliability was found for VORT (ICC3,K = 0.97) and VUCM (ICC3,K = 0.92), whereas good reliability was observed for ΔV (ICC3,K = 0.84). Bland-Altman plots reveled no systematic differences. SEM% values were 24.57 %, 26.80 % and 12.49 % for VORT, VUCM and ΔV respectively, while the normalized MDC% values were 68.12 %, 74.30 % and 34.61 % for VORT, VUCM and ΔV respectively. Our results support the use of UCM as a reliable method for investigating the structure of movement variability. The excellent measurement properties make the UCM a promising tool for tracking changes in motor behavior over time (i.e., effects of interventions in prospective studies).

The role of loneliness in the association between sexual orientation and depressive symptoms among older adults: A prospective cohort study.

BACKGROUND: This study aims to understand the mechanisms contributing to the elevated risk of depression among sexual minority older adults compared to heterosexuals. Specifically, the role of loneliness as a potential mediator is investigated to inform targeted interventions for preventing depression in sexual minority populations. METHODS: Data from the English Longitudinal Study of Ageing, focusing on adults aged over 50, were analysed. Sexual orientation (sexual minority or heterosexual) and loneliness scores (UCLA scale) were assessed at wave six (2010-2011), while depressive symptoms (CESD) were assessed at wave seven (2013-14). Linear regression models and mediation analyses, using g-computation formula and adjusted for confounders, were conducted. RESULTS: The sample included 6794 participants, with 478 (7.0 %) identifying as sexual minorities. After adjustments, sexual minorities scored higher on depressive symptoms at wave seven (mean difference): 0.23, 95 % CI 0.07 to 0.39) and loneliness at wave six (MD: 0.27, 95 % CI 0.08 to 0.46). Loneliness was positively associated with depressive symptoms (coefficient: 0.27, 95 % CI 0.26 to 0.29). In mediation analyses, loneliness explained 15 % of the association between sexual orientation and subsequent depressive symptoms. LIMITATIONS: The dataset used sexual behaviour rather than desire and identity, potentially skewing representation of sexual minorities. Additionally, transgender older adults were not included due to limited gender diversity reported within the ELSA dataset. CONCLUSIONS: Loneliness appears to be a significant modifiable mechanism contributing to the heightened risk of depressive symptoms in sexual minority older adults compared with their heterosexual counterparts.

Prehospital early warning scores for adults with suspected sepsis: the PHEWS observational cohort and decision-analytic modelling study.

Background: Guidelines for sepsis recommend treating those at highest risk within 1 hour. The emergency care system can only achieve this if sepsis is recognised and prioritised. Ambulance services can use prehospital early warning scores alongside paramedic diagnostic impression to prioritise patients for treatment or early assessment in the emergency department. Objectives: To determine the accuracy, impact and cost-effectiveness of using early warning scores alongside paramedic diagnostic impression to identify sepsis requiring urgent treatment. Design: Retrospective diagnostic cohort study and decision-analytic modelling of operational consequences and cost-effectiveness. Setting: Two ambulance services and four acute hospitals in England. Participants: Adults transported to hospital by emergency ambulance, excluding episodes with injury, mental health problems, cardiac arrest, direct transfer to specialist services, or no vital signs recorded. Interventions: Twenty-one early warning scores used alongside paramedic diagnostic impression, categorised as sepsis, infection, non-specific presentation, or other specific presentation. Main outcome measures: Proportion of cases prioritised at the four hospitals; diagnostic accuracy for the sepsis-3 definition of sepsis and receiving urgent treatment (primary reference standard); daily number of cases with and without sepsis prioritised at a large and a small hospital; the minimum treatment effect associated with prioritisation at which each strategy would be cost-effective, compared to no prioritisation, assuming willingness to pay £20,000 per quality-adjusted life-year gained. Results: Data from 95,022 episodes involving 71,204 patients across four hospitals showed that most early warning scores operating at their pre-specified thresholds would prioritise more than 10% of cases when applied to non-specific attendances or all attendances. Data from 12,870 episodes at one hospital identified 348 (2.7%) with the primary reference standard. The National Early Warning Score, version 2 (NEWS2), had the highest area under the receiver operating characteristic curve when applied only to patients with a paramedic diagnostic impression of sepsis or infection (0.756, 95% confidence interval 0.729 to 0.783) or sepsis alone (0.655, 95% confidence interval 0.63 to 0.68). None of the strategies provided high sensitivity (> 0.8) with acceptable positive predictive value (> 0.15). NEWS2 provided combinations of sensitivity and specificity that were similar or superior to all other early warning scores. Applying NEWS2 to paramedic diagnostic impression of sepsis or infection with thresholds of > 4, > 6 and > 8 respectively provided sensitivities and positive predictive values (95% confidence interval) of 0.522 (0.469 to 0.574) and 0.216 (0.189 to 0.245), 0.447 (0.395 to 0.499) and 0.274 (0.239 to 0.313), and 0.314 (0.268 to 0.365) and 0.333 (confidence interval 0.284 to 0.386). The mortality relative risk reduction from prioritisation at which each strategy would be cost-effective exceeded 0.975 for all strategies analysed. Limitations: We estimated accuracy using a sample of older patients at one hospital. Reliable evidence was not available to estimate the effectiveness of prioritisation in the decision-analytic modelling. Conclusions: No strategy is ideal but using NEWS2, in patients with a paramedic diagnostic impression of infection or sepsis could identify one-third to half of sepsis cases without prioritising unmanageable numbers. No other score provided clearly superior accuracy to NEWS2. Research is needed to develop better definition, diagnosis and treatments for sepsis. Study registration: This study is registered as Research Registry (reference: researchregistry5268). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/136/10) and is published in full in Health Technology Assessment; Vol. 28, No. 16. See the NIHR Funding and Awards website for further award information.

Sepsis is a life-threatening condition in which an abnormal response to infection causes heart, lung or kidney failure. People with sepsis need urgent treatment. They need to be prioritised at the emergency department rather than waiting in the queue. Paramedics attempt to identify people with possible sepsis using an early warning score (based on simple measurements, such as blood pressure and heart rate) alongside their impression of the patient's diagnosis. They can then alert the hospital to assess the patient quickly. However, an inaccurate early warning score might miss cases of sepsis or unnecessarily prioritise people without sepsis. We aimed to measure how accurately early warning scores identified people with sepsis when used alongside paramedic diagnostic impression. We collected data from 71,204 people that two ambulance services transported to four different hospitals in 2019. We recorded paramedic diagnostic impressions and calculated early warning scores for each patient. At one hospital, we linked ambulance records to hospital records and identified who had sepsis. We then calculated the accuracy of using the scores alongside diagnostic impression to diagnose sepsis. Finally, we used modelling to predict how many patients (with and without sepsis) paramedics would prioritise using different strategies based on early warning scores and diagnostic impression. We found that none of the currently available early warning scores were ideal. When they were applied to all patients, they prioritised too many people. When they were only applied to patients whom the paramedics thought had infection, they missed many cases of sepsis. The NEWS2, score, which ambulance services already use, was as good as or better than all the other scores we studied. We found that using the NEWS2, score in people with a paramedic impression of infection could achieve a reasonable balance between prioritising too many patients and avoiding missing patients with sepsis.

Endoscopic versus laparoscopic management of noninvasive upper tract urothelial carcinoma: 20-year single center experience.

PURPOSE: We compare the outcomes of endoscopic surgery to laparoscopic nephroureterectomy for the management of specifically noninvasive upper tract urothelial carcinoma. MATERIALS AND METHODS: A retrospective database review identified consecutive patients with clinically noninvasive upper tract urothelial carcinoma who underwent endoscopic surgery (59, via ureteroscopic ablation or percutaneous resection) or laparoscopic nephroureterectomy (70) at a single center during 20 years (1991 to 2011). Overall survival, upper tract urothelial carcinoma specific survival, upper tract recurrence-free survival, intravesical recurrence-free survival, progression-free survival and renal unit survival were estimated using Kaplan-Meier methods, with differences assessed using the log rank test. RESULTS: Median age and followup were 74.8 years and 50 months, respectively. Overall renal preservation in the endoscopic group was high (5-year renal unit survival 82.5%), although this came at a cost of high local recurrence (endoscopic surgery 5-year recurrence-free survival 49.3%, laparoscopic nephroureterectomy 100%, p <0.0001). For G1 upper tract urothelial carcinoma, endoscopic surgery 5-year disease specific survival (100%) was equivalent to that of laparoscopic nephroureterectomy (100%). However, laparoscopic nephroureterectomy demonstrated superior disease specific survival to endoscopic surgery for G2 disease (91.7% vs 62.5%, p = 0.037) and superior progression-free survival for G3 disease (88.9% vs 55.6%, p = 0.033). CONCLUSIONS: For G1 upper tract urothelial carcinoma, endoscopic management can provide effective oncologic control and renal preservation. However, endoscopic management should not be considered for higher grade disease except in compelling imperative cases or in patients with poor life expectancy as oncologic outcomes are inferior to those of laparoscopic nephroureterectomy.