Dissociative ionization and Coulomb explosion of CH4 in two-color asymmetric intense laser fields.

Directional fragment ejection from a tetrahedral molecule CH4 in linearly polarized two-color (ω and 2ω) asymmetric intense laser fields (50 fs, 1.4 × 1014 W cm-2, 800 nm and 400 nm) has been studied by three-dimensional ion coincidence momentum imaging. The H+ fragment produced from dissociative ionization, CH4 → H+ + CH3 + e-, is preferentially ejected on the larger amplitude side of the laser electric fields. Comparison with theoretical predictions by weak-field asymptotic theory shows that the observed asymmetry can be understood by the orientation selective tunneling ionization from the triply degenerated highest occupied molecular orbital (1t2) of CH4. A similar directional ejection of H+ was also observed for the low kinetic energy components of the two-body Coulomb explosion, CH4 → H+ + CH3+ + 2e-. On the other hand, the fragment ejection in the opposite direction were observed for the high energy component, as well as H2+ produced from the Coulomb explosion CH4 → H2+ + CH2+ + 2e-. Possible origins of the characteristic fragmentation are discussed.

Cumulative effects of pre-pandemic vulnerabilities and pandemic-related hardship on psychological distress among pregnant individuals.

OBJECTIVE: Our primary objective was to determine whether pre-existing vulnerabilities and resilience factors combined with objective hardship resulted in cumulative (i.e., additive) effects on psychological distress in pregnant individuals during the COVID-19 pandemic. A secondary objective was to determine whether any of the effects of pandemic-related hardship were compounded (i.e., multiplicative) by pre-existing vulnerabilities. METHOD: Data are from a prospective pregnancy cohort study, the Pregnancy During the COVID-19 Pandemic study (PdP). This cross-sectional report is based upon the initial survey collected at recruitment between April 5, 2020 and April 30, 2021. Logistic regressions were used to evaluate our objectives. RESULTS: Pandemic-related hardship substantially increased the odds of scoring above the clinical cut-off on measures of anxiety and depression symptoms. Pre-existing vulnerabilities had cumulative (i.e., additive) effects on the odds of scoring above the clinical cut-off on measures of anxiety and depression symptoms. There was no evidence of compounding (i.e., multiplicative) effects. Social support had a protective effect on anxiety and depression symptoms, but government financial aid did not. CONCLUSION: Pre-pandemic vulnerability and pandemic-related hardship had cumulative effects on psychological distress during the COVID-19 pandemic. Adequate and equitable responses to pandemics and disasters may require more intensive supports for those with multiple vulnerabilities.

A pilot study on the use of the super dimension navigation system for optimal cryobiopsy location in interstitial lung disease diagnostics.

BACKGROUND: Transbronchial cryobiopsies has become increasingly important in the diagnostic workup for interstitial lung diseases. The rate of complications and mortality are low compared to surgical lung biopsies, but the diagnostic yield is not as high. The reason for the lower diagnostic yield could in some cases be explained by biopsies taken too centrally or in less affected areas. In this pilot study we examined the feasibility of using the electromagnetic navigation system, superDimension (SD), when performing cryobiopsies to increase the diagnostic yield. METHODS: Electromagnetic navigation bronchoscopy and cryobiopsies were performed using SD. An electromagnetic board placed on the back of the patient and a position sensor at the tip of the navigational probe created a real-time 3D reconstruction of previously acquired computer tomography images. The procedure was performed with the patients in general anesthesia using a rigid bronchoscope when performed in Florence and with a flexible bronchoscope through an orotracheal tube when performed in Aarhus. RESULTS: In total, 18 patients were included. Five patients were excluded, partly due to technical difficulties. Disposable 1.7 mm cryoprobes were used in Aarhus, and reusable 1.9 mm probes in Florence. Pneumothorax was detected in three (23%), mild hemorrhage was seen in one (8%) and moderate hemorrhage in six (46%). The biopsies contributed to the diagnosis in 11 of the patients (85%). CONCLUSION: Using superDimension electromagnetic navigation system when performing cryobiopsies is feasible. A larger prospective trial is necessary to homogenize the technique between centres and to evaluate diagnostic advantage and complications.

Helicity-dependent dissociative tunneling ionization of CF4 in multicycle circularly polarized intense laser fields.

Dissociative tunneling ionization of tetrafluoromethane (CF4) in circularly polarized ultrashort intense laser fields (35 fs, 0.8 × 1014 W cm-2, 1035 nm), CF4 → CF4+ + e- → CF3+ + F + e-, has been studied by three-dimensional electron-ion coincidence momentum imaging. The photoelectron angular distribution in the recoil frame revealed that the dissociative tunneling ionization occurs efficiently when the laser electric field points from F to C. The obtained results are qualitatively consistent with the theoretical predictions by the weak-field asymptotic theory (WFAT) for tunneling ionization from the highest and next-highest occupied molecular orbitals, HOMO (1t1), and HOMO-1 (4t2), respectively. On the other hand, the angular distribution shows clear dependences on the polarization helicity, indicating that the breaking of the C-F bonds is sensitive to the helicity of the multicycle circularly polarized laser fields.

Fear of COVID-19, mental health, and pregnancy outcomes in the pregnancy during the COVID-19 pandemic study: Fear of COVID-19 and pregnancy outcomes.

BACKGROUND: Sustained fear during pregnancy has the potential to increase psychological distress and obstetric risk. This study aimed to (1) identify factors and characteristics associated with fear of COVID-19, (2) investigate the relationship between fear of COVID-19 and maternal anxiety and depression, and (3) determine the relationship between fear of COVID-19 and pregnancy outcomes. METHODS: 9251 pregnant Canadians were recruited between April - December 2020. Participants self-reported (scale of 0-100) the degree of threat they perceived from the SARS-CoV-2 virus in relation to themselves and their unborn baby. RESULTS: Mean fear scores indicated moderate to elevated concern. In multivariable linear regression, fear of COVID-19 was associated with food insecurity, ethnicity, geographic location, history of anxiety prior to pregnancy, having a chronic health condition, pre-pregnancy BMI, parity, and stage of pregnancy at study enrollment. Higher COVID-19 fear was associated with increased odds of depression, adjusted odds ratio (aOR) = 1.75, p < 0.001, 95% CI 1.66-1.85, and anxiety, aOR=2.04, p < 0.001, 95% CI 1.94-2.15). Furthermore, fear of COVID-19 was associated with a 192-gram reduction in infant birthweight, and a 6.1-day reduction in gestational age at birth. LIMITATIONS: The sample has higher education compared to the Canadian population and cannot test causal effects. CONCLUSION: This study suggests that sociodemographic, health, and obstetric factors may contribute to increased fear of COVID-19 and associated adverse psychological and pregnancy outcomes.

Neighbourhood characteristics, lifestyle factors, and child development: Secondary analysis of the All our families cohort study.

Background: Neighbourhood characteristics have been found to influence child development, but little is known about lifestyle factors that may moderate this relationship, which can provide modifiable targets for policies and programing. This study investigated the association between neighbourhood characteristics (e.g., deprivation, disorder) during pregnancy and child development at age 5 in relation to various lifestyle factors (e.g., physical activity, parent-child reading, community resource use) during early childhood. Methods: A secondary analysis was conducted using multilevel modeling of data from the All Our Families cohort, recruited in Canada from 2008 to 2010. Participants self-reported on demographics during pregnancy, lifestyle factors at 3 years, and child development at 5 years using the Ages and Stages Questionnaire (ASQ-3). Neighbourhood deprivation was evaluated using the Vancouver Area Deprivation Index (VANDIX), while disorder was measured using police services' community crime reports. Results: Geocoded information was available for 2,444 participants. After adjusting for covariates, multilevel modeling indicated a significant negative association between neighbourhood deprivation and overall child development (b = -.726, 95% CI: -1.344, -.120). Parent-child reading was found to be a significant moderator of the effect of neighbourhood disorder (b = .005, 95% CI: .001, .009). There were no statistically significant moderation effects for physical activity or community resource use. Conclusion: Neighbourhood deprivation during pregnancy is associated with early child development. Parent-child reading may function as a protective factor in the presence of higher neighbourhood disorder. Overall, neighbourhood-level effects should be considered in policies and community programs that promote family and child well-being.

"To have and then lose the safety net" - Female cancer survivors' experiences of the process of becoming ready to return to work.

BACKGROUND: Validation studies have not been able to confirm the stage-specific understanding as operationalised in the readiness for return to work (RRTW) questionnaire. OBJECTIVE: To explore retrospectively how working female cancer survivors experienced the process of becoming ready to RTW during and beyond participation in an occupational rehabilitation intervention and thereby expand the understanding of the RRTW construct. METHODS: A qualitative research design was employed. Thirteen female cancer survivors were included for semi-structured interviews one to two years after they had completed active treatment and returned to work. The RRTW construct guided data generation and analysis. Content analysis was performed in four analytical steps that combined a concept-driven and a data-driven analytic strategy. RESULTS: Three themes were identified; "To have and then lose the safety net", "Realise a changed life situation", "Strive to balance work and everyday life". In a time span of approximately one to two years (from receiving treatment, being enrolled in an intervention and to gradually returning to work); the identified themes were interdependent of each other as one theme gradually evolved to the next theme in the process of engaging in sustained work participation. CONCLUSIONS: The present study points towards continuous development of the RRTW construct and whether the addition of a preparedness dimension would improve validity.

Enhancement of Above Threshold Ionization in Resonantly Excited Helium Nanodroplets.

Clusters and nanodroplets hold the promise of enhancing high-order nonlinear optical effects due to their high local density. However, only moderate enhancement has been demonstrated to date. Here, we report the observation of energetic electrons generated by above-threshold ionization (ATI) of helium (He) nanodroplets which are resonantly excited by ultrashort extreme ultraviolet (XUV) free-electron laser pulses and subsequently ionized by near-infrared (NIR) or near-ultraviolet (UV) pulses. The electron emission due to high-order ATI is enhanced by several orders of magnitude compared with He atoms. The crucial dependence of the ATI intensities with the number of excitations in the droplets suggests a local collective enhancement effect.

Factors affecting patient adherence to publicly funded colorectal cancer screening programmes: a systematic review.

OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer. Many countries in Europe have already implemented systematic screening programmes as per the recommendations by the European Union. The impact of screening is highly dependent on participation rates. The aim of the study was to identify barriers, facilitators and modifiers to participation in systematised, stool sample-based, publicly financed CRC screening programmes. STUDY DESIGN: Systematic review. METHODS: A systematic search in PubMed, Embase, MEDLINE, CINAHL, Cochrane CENTRAL, Google Scholar and PsycINFO was undertaken. We included both qualitative and quantitative studies reporting on barriers and facilitators (excluding sociodemographic variables) to participation in stool sample-based CRC screening. Barriers and facilitators to participation were summarised and analysed. RESULTS: The inclusion criteria were met in 21 studies. Reported barriers and facilitators were categorised into the following seven themes (examples): psychology (fear of cancer), religion (believing cancer is the will of God), logistics (not knowing how to conduct the test), health-related factors (mental health), knowledge and awareness (lack of knowledge about the test), role of the general practitioner (being supported in taking the test by the general practitioner), and environmental factors (knowing someone who has participated in a screening programme). Six studies reported that non-participation was not due to a negative attitude towards screening for CRC. CONCLUSION: Many barriers to screening were found. It is important to work with peoples' fear of screening. Moreover, this review suggests that it might be possible to increase participation rates, if the population-wide awareness and knowledge of potential health benefits of CRC screening are increased and proper logistical support is provided.

Mercury bioaccumulation pathways in tusk (Brosme brosme) from Sognefjord, Norway: Insights from C and N isotopes.

Seafood is the main source of methylmercury (MeHg) exposure for humans and elevated total mercury (Hg) concentrations have been reported in marine fish from Norwegian fjords compared with offshore areas. Hg in tusk fillets (n = 201) and liver samples (n = 177) were measured in individuals from different habitats including offshore, coastal area, outer and inner Sognefjord. Specifically, the effects of habitat, energy sources and trophic complexity on Hg bioaccumulation pathways in tusk (Brosme brosme) were investigated using stable isotopes of carbon (δ13C) and nitrogen (δ15N). The concentrations of Hg in tusk increased from offshore towards inner Sognefjord. While Hg concentrations in sediment were at background levels, tusk fillet samples from 7 of 8 sites in Sognefjord had higher Hg levels than the maximum level set by European Union. Based on these findings, human consumption advice for tusk from Sognefjord was issued by the Norwegian Food Safety Authority. δ13C values in tusk successfully discriminated individuals from different habitats and were positively correlated to Hg concentrations in tusk across individuals, sites and habitats, outlining the potential importance of terrestrial carbon and most likely the atmospheric deposition of Hg from the catchment to the overall Hg bioaccumulation and exposure regime in tusk. Additionally, we postulate that the effects of terrestrial carbon sources increased towards inner Sognefjord and likely influenced Hg bioavailability throughout the food web. In contrast, δ15N values were patchy throughout the fjord system and although trophic position explained some of the Hg variation between individual fish, it was not correlated with Hg variation across sites and habitats. Our results suggest that tusk can accumulate high levels of Hg in fjord ecosystems and that catchment runoff is likely an important driver of Hg bioaccumulation in this species.

Levels of omega 3 fatty acids, vitamin D, dioxins and dioxin-like PCBs in oily fish; a new perspective on the reporting of nutrient and contaminant data for risk-benefit assessments of oily seafood.

Oily seafood is an important food source which contains several key nutrients beneficial for human health. On the other hand, oily seafood also contains persistent organic pollutants (POPs), including the dioxin-like compounds (DLCs) polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) and dioxin-like-polychlorinated biphenyls (dl-PCBs), potentially detrimental to human health. For a comprehensive comparison of the beneficial and potentially adverse health effects of seafood consumption, risk-benefit analyses are necessary. Risk-benefit analyses require reliable quantitative data and sound knowledge of uncertainties and potential biases. Our dataset comprised more than 4000 analyses of DLCs and more than 1000 analyses each of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and vitamin D in the three most important Norwegian commercial oily seafood species: Atlantic herring (Clupea harengus), Atlantic mackerel (Scomber scombrus) and farmed Atlantic salmon (Salmo salar). The levels of several DLC congeners were below the limit of quantification (LOQ), making estimation of true levels challenging. We demonstrate that the use of upper bound substitution of censored data will overestimate, while lower bound substitution will underestimate the actual levels of DLCs. Therefore, we implement an alternative robust statistical method by combining Maximum Likelihood Estimation, Regression on Order Statistics and Kaplan-Meier analyses, which is better suited for providing estimations of levels of these contaminants in seafood. Moreover, we illustrate the impact of the toxic equivalency factor (TEF) system on estimation of the sums of DLCs by comparing the TEF system to an alternative system of relative effect potency (REP) factors (Consensus Toxicity Factors). The levels of nutrients and contaminants were related to adequate intake (AI) and tolerable weekly intake (TWI), respectively. We used AI and the TWI values established by the European Food Safety Authority (EFSA). The benefit and the risk were further viewed in the context of the Norwegian average intake of oily fish, and the Norwegian governmental official dietary recommendations of oily fish. Our results showed that both benefit and risk are met at the levels found of nutrients and DLCs in oily seafood. The comprehensive quantitative data presented here will be a key for future risk-benefit assessment of oily fish consumption. Together, our results underline that a refined formalized integrative risk-benefit assessment of oily fish in the diet is warranted, and that the data and methodology presented in this study are highly relevant for future integrated and multidisciplinary assessment of both risks and benefits of seafood consumption for human health.

Health-related quality of life and well-being in parents of infants and toddlers with cancer.

Background: The unique psychosocial needs of parents and caregivers of young children with cancer are poorly understood. The aims of the present study were to examine health-related quality of life (hrqol), stress, and psychological distress in parents of young children (0-4 years) diagnosed with cancer; and the associations between parent psychosocial functioning and child treatment characteristics. Methods: Parents (n = 35) with a child (n = 19 male, 54.3%) 0-48 months of age (median: 31.06 months) on active cancer therapy were recruited. Parents completed questionnaires related to demographics, parent hrqol, parenting stress, posttraumatic stress symptoms, and parent psychological distress. Results: Parents reported clinically elevated parenting stress (5.9%), posttraumatic stress symptoms (18.2%), and psychological distress (21.9%). Compared with population norms, parents reported lower hrqol in the vitality (t = 5.37, p < 0.001), mental health (t = 4.02, p < 0.001), role limitation-emotional (t = 3.52, p < 0.001), and general health perceptions (t = 2.25, p = 0.025) domains. Social functioning (ß = 0.33, p = 0.041) predicted general health perceptions; vitality (ß = 0.30, p = 0.134) and parent mental health (ß = 0.24, p = 0.285) did not [F(3,29) = 12.64, p < 0.001, R2 = 0.57]. Conclusions: A subset of parents of young children on active cancer treatment experience clinically elevated psychosocial symptoms. Having poor social connections put parents at risk of perceiving their health more poorly in general. Supports that focus on preventing the emergence of clinically significant distress should focus on parents of young children with cancer who are most at risk of poor outcomes.

Mesh versus suture in elective repair of umbilical hernia: systematic review and meta-analysis.

BACKGROUND: Mesh repair of umbilical hernia has been associated with a reduced recurrence rate compared with suture closure, but potentially at the expense of increased postoperative complications and chronic pain. The objective of this systematic review and meta-analysis was to examine the outcomes after elective open mesh and suture repair for umbilical hernia in adults. METHODS: A literature search was conducted to identify studies presenting original data on elective open mesh and suture repair of umbilical hernia. The primary outcome was hernia recurrence. Secondary outcomes included surgical-site infection (SSI), seroma, haematoma and chronic pain. Meta-analyses were undertaken. RESULTS: The search resulted in 5353 hits and led to 14 studies being included (6 RCTs and 8 observational studies) describing a total of 2361 patients. Compared with suture, mesh repair was associated with a lower risk of recurrence (risk ratio (RR) 0·48, 95 per cent c.i. 0·30 to 0·77), with number needed to treat 19 (95 per cent c.i. 14 to 31). Mesh repair was associated with a higher risk of seroma (RR 2·37, 1·45 to 3·87), with number needed to harm 30 (17 to 86). There was no significant difference in the risk of SSI, haematoma or chronic pain. CONCLUSION: The use of mesh in elective repair of umbilical hernia reduced the risk of recurrence compared with suture closure without altering the risk of chronic pain.

ANTECEDENTES: La reparación con malla de la hernia umbilical se ha asociado con una tasa menor de recidivas en comparación con el cierre con suturas, pero potencialmente a expensas de un aumento de complicaciones postoperatorias y dolor crónico. El objetivo de esta revisión sistemática y metaanálisis fue examinar los resultados después de reparación abierta electiva con malla o suturas para la reparación de una hernia umbilical en adultos. MÉTODOS: Se llevó a cabo una búsqueda en la literatura para identificar estudios que presentaban datos originales sobre la reparación abierta electiva con malla y sutura de la hernia umbilical. El resultado primario fue la recidiva herniaria. Los resultados secundarios incluyeron la infección del sitio quirúrgico (surgical site infection, SSI), seroma, hematoma y dolor crónico. Se realizaron metaanálisis. RESULTADOS: En la búsqueda identificaron 5.353 documentos, incluyéndose 14 estudios (6 ensayos clínicos aleatorizados, 8 estudios observacionales) que presentaban datos de un total de 2.361 pacientes. En comparación con la sutura, la reparación con malla se asoció con un menor riesgo de recidiva (tasa de riesgo, risk ratio, RR 0,48, i.c. del 95% 0,30 a 0,77) y número necesario para tratar de 19 (i.c. del 95% 14 a 31). La reparación con malla se asoció con un mayor riesgo de seroma (RR 2,37, i.c. del 95% 1,45 a 3,87) y número necesario para provocar daño de 30 (i.c. del 95% 17 a 86). No hubo diferencia significativa en el riesgo de SSI, hematoma o dolor crónico. CONCLUSIÓN: El uso de malla en la reparación electiva de la hernia umbilical redujo el riesgo de recidiva en comparación con el cierre con sutura, sin modificar el riesgo de dolor crónico.

Reduction in myocardial strain is evident in adolescents and young adults with obesity and type 2 diabetes.

AIMS/HYPOTHESIS: Heart failure is a complication of type 2 diabetes (T2DM). Echocardiography can identify subclinical systolic dysfunction in adults with T2DM. We hypothesized that reduced systolic strain was present in youth with T2DM. METHODS: Global longitudinal strain (GLS) was measured in 151 subjects with T2DM matched to lean (L = 146), and obese (O = 162) subjects (23.0 ± 4.0 years, 35% male, 63% African American). Anthropometrics, BP, HR, labs, and echocardiograms were obtained. ANOVA was performed to compare differences among groups, and ANCOVA to determine if T2DM remained an independent predictor after corrections. RESULTS: BP, lipid levels, and metabolic control worsened and GLS was reduced from L to O to T2DM. BMI was lower in L than O or T2DM. Global longitudinal strain rate (GLSR) was lower and LVM/ht2.7 was higher in O and T2DM as compared to L (all P ≤ .05). Presence of T2DM was an independent determinant of GLS and GLSR adjusted for most CV risk factors, but lost significance when BMI was added to the model. GLS = -21.6-age*0.088 - male*1.8 + 0.12*BMI + 0.045*DBP + 0.058*HR - 0.023*HDL (R2 = 0.38, P ≤ .0001); GLSR = -1.20-male*0.093 + WHR*0.48 + DBP*0.0029 (R2 = 0.23, P ≤ .0001). CONCLUSION: Both adiposity and T2DM have a deleterious effect on systolic cardiac function. Treatment of obesity in youth is necessary for prevention of future heart failure.

Molecular Symmetry-Mixed Dichroism in Double Photoionization of H_{2}.

Dichroism in double photoionization of H_{2} molecules by elliptically polarized extreme ultraviolet pulses is formulated analytically as a sum of atomiclike dichroism (AD) and molecular symmetry-mixed dichroism (MSMD) terms. The MSMD originates from an interplay of ^{1}Σ_{u}^{+} and ^{1}Π_{u}^{+} continuum molecular ionization amplitudes. For detection geometries in which the AD vanishes, numerical results for the sixfold differential probabilities for opposite pulse helicities show that the MSMD is significant in the electron momentum and angular distributions and is controllable by the ellipticity.

Influence of Cardiac CT based disease severity and clinical symptoms on the diagnostic performance of myocardial perfusion.

We aimed to identify factors influencing the sensitivity of perfusion imaging after an initial positive coronary computed tomography angiography (CCTA) using invasive coronary angiography (ICA) with conditional fractional flow reserve (FFR) as reference. Secondly we aimed to identify factors associated with revascularisation and to evaluate treatment outcome after ICA. We analysed 292 consecutive patients with suspected significant coronary artery disease (CAD) at CCTA, who underwent perfusion imaging with either cardiac magnetic resonance (CMR) or myocardial perfusion scintigraphy (MPS) followed by ICA with conditional FFR. Stratified analysis and uni- and multiple logistic regression analyses were performed to identify predictors of diagnostic agreement between perfusion scans and ICA and predictors of revascularisation. Myocardial ischemia evaluated with perfusion scans was present in 65/292 (22%) while 117/292 (40%) had obstructive CAD evaluated by ICA. Revascularisation rate was 90/292 (31%). The overall sensitivity for perfusion scans was 39% (30-48), specificity 89% (83-93), PPV 69% (57-80) and NPV 68% (62-74). Stratified analysis showed higher sensitivities in patients with multi-vessel disease at CCTA 49% (37-60) and typical chest pain 50% (37-60). Predictors of revascularisation were multi-vessel disease by CCTA (OR 3.51 [1.91-6.48]) and a positive perfusion scan (OR 4.69 [2.49-8.83]). The sensitivity for perfusion scans after CCTA was highest in patients with typical angina and multiple lesions at CCTA and predicted diagnostic agreement between perfusion scans and ICA. Abnormal perfusion and multi vessel disease at CCTA predicted revascularisation.

Diabetic retinopathy in people with Type 2 diabetes and obesity treated by Roux-en-Y gastric bypass compared with non-operated controls: with focus on the role of diabetes remission in a cross-sectional and a 6-year follow-up study.

AIM: Whether or not Roux-en-Y gastric bypass (RYGB) and the derived metabolic improvements are beneficial to diabetic retinopathy is controversial. We aimed to determine the presence and development of retinopathy in individuals with obesity and Type 2 diabetes treated by RYGB compared with non-operated controls, and to determine the role of diabetes remission. METHODS: We graded fundus photography using the Wisconsin Epidemiologic Study of Diabetic Retinopathy in 96 individuals with obesity and Type 2 diabetes treated by RYGB 6 years after surgery compared with 48 non-operated controls. In a subsample, we investigated the development of retinopathy over time. In the secondary analysis, we divided the RYGB group according to diabetes remission. RESULTS: RYGB surgery was not statistically associated with less retinopathy [relative risk (RR) 0.82, 95% CI 0.59 to 1.14], when adjusted for diabetes duration, sex, age and BMI. During 5.9 years of follow-up, retinopathy grading in the RYGB group was unchanged, whereas the control group displayed worse grading by 0.69 steps (95% CI 0.18 to 1.19). The RYGB group with diabetes remission (52%) showed a trend towards less retinopathy [adjusted RR (aRR) 0.45; 95% CI 0.19 to 1.06] than controls, and less retinopathy (aRR 0.33; 95% CI 0.11 to 0.94) than the RYGB group without remission in the cross-sectional data. CONCLUSIONS: In a cross-sectional setting, individuals with Type 2 diabetes treated by RYGB showed a tendency towards less retinopathy than non-operated controls, in particular diabetes remission following RYGB was associated with less retinopathy. Moreover after 5.9 years, retinopathy in the RYGB group had progressed less than in the control group. (Clinical Trial Registry No: NCT02625649).

A randomized controlled trial of working memory and processing speed training in schizophrenia.

BACKGROUND: Although prior research has shown that cognitive training may improve cognition for schizophrenia patients, it is currently unclear which domains of cognition should be targeted in training. One suggestion is to target low- or mid-level cognitive processes. In particular, working memory (WM) and processing speed (PS) have been named as two key areas of impairment in schizophrenia, and two domains of cognition that are linked to higher-order cognition and daily functioning. This study aimed to investigate the near-transfer (transfer of gains to related contexts), far-transfer (transfer of gains to unrelated contexts), and real-world gains associated with WM and PS training in schizophrenia. METHODS: Eighty-three participants with schizophrenia were recruited and randomly assigned to computerized WM training, PS training, or a no-training control group. Outcome measures included WM, PS, fluid intelligence, executive functioning, social cognition, and daily functioning and symptoms. RESULTS: PS training led to significant gains in untrained PS tasks, as well as gains in far-transfer tasks that required speed of processing. WM training did not lead to gains in untrained WM tasks and showed inconsistent effects on some far-transfer tasks. CONCLUSIONS: These results suggest some benefit of domain-specific cognitive training, specifically PS training, in schizophrenia. Far-transfer of gains to other cognitive domains and to real-world functioning may not occur after targeted WM or PS training, though non-specific effects (e.g. through behavioral activation, increased motivation) may lead to improvements in some tasks. Future studies should continue to investigate the mechanisms by which cognitive training may enhance cognition and functioning in schizophrenia.

Pre-clinical evaluation of novel mucoadhesive bilayer patches for local delivery of clobetasol-17-propionate to the oral mucosa.

Oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS) are chronic inflammatory conditions often characterised by erosive and/or painful oral lesions that have a considerable impact on quality of life. Current treatment often necessitates the use of steroids in the form of mouthwashes, creams or ointments, but these are often ineffective due to inadequate drug contact times with the lesion. Here we evaluate the performance of novel mucoadhesive patches for targeted drug delivery. Electrospun polymeric mucoadhesive patches were produced and characterised for their physical properties and cytotoxicity before evaluation of residence time and acceptability in a human feasibility study. Clobetasol-17-propionate incorporated into the patches was released in a sustained manner in both tissue-engineered oral mucosa and ex vivo porcine mucosa. Clobetasol-17 propionate-loaded patches were further evaluated for residence time and drug release in an in vivo animal model and demonstrated prolonged adhesion and drug release at therapeutic-relevant doses and time points. These data show that electrospun patches are adherent to mucosal tissue without causing tissue damage, and can be successfully loaded with and release clinically active drugs. These patches hold great promise for the treatment of oral conditions such as OLP and RAS, and potentially many other oral lesions.

Diagnosing coronary artery disease after a positive coronary computed tomography angiography: the Dan-NICAD open label, parallel, head to head, randomized controlled diagnostic accuracy trial of cardiovascular magnetic resonance and myocardial perfusion scintigraphy.

Aims: Perfusion scans after coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD) may reduce unnecessary invasive coronary angiographies (ICAs). However, the diagnostic accuracy of perfusion scans after primary CCTA is unknown. The aim of this study was to determine the diagnostic accuracy of cardiac magnetic resonance (CMR) and myocardial perfusion scintigraphy (MPS) against ICA with fractional flow reserve (FFR) in patients suspected of CAD by CCTA. Methods and results: Included were consecutive patients (1675) referred to CCTA with symptoms of CAD and low/intermediate risk profile. Patients with suspected CAD based on CCTA were randomized 1:1 to CMR or MPS followed by ICA with FFR. Obstructive CAD was defined as FFR ≤ 0.80 or > 90% diameter stenosis by visual assessment. After initial CCTA, 392 patients (23%) were randomized; 197 to CMR and 195 to MPS. Perfusion scans and ICA were completed in 292 patients (CMR 148, MPS 144). Based on the ICA, 117/292 (40%) patients were classified with CAD. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for CMR were 41%, 95% CI [28-54], 84% [75-91], 62% [45-78], and 68% [58-76], respectively. For the MPS group 36% [24-50], 94% [87-98], 81% [61-93], and 68% [59-76], respectively. Conclusion: Patients with low/intermediate CAD risk and a positive CCTA scan represent a challenge to perfusion techniques indicated by the low sensitivity of both CMR and MPS with FFR as a reference. The mechanisms underlying this discrepancy need further investigation.