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Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Background: Cognitive impairment has been reported in patients with Major Depressive Disorder (MDD). This study aims to explore the association between lifestyle habits and health-related factors and the presence of cognitive symptoms in MDD patients. Methods: Demographic, clinical, health-related variables and cognitive scores measured with the Cambridge Neuropsychological Test Automated Battery (CANTAB) were compared between 74 patients with current MDD and 68 healthy controls (HC). To test the hypothesis of associated factors to cognitive symptoms, multivariate backward stepwise linear regression models were run. Results: Significant neuropsychological deficits were evident in MDD compared with HC in the global cognitive index (F=8.29; df=1, 140; p=0.005). In the regression analysis performed on MDD and HC, years of schooling (β=-0.11; p=

Understanding the influence of the temperature on the performance of perovskite solar cells (PSCs) is essential for device optimization and for improving the stability of devices in outdoor conditions. In addition, knowing the transient thermal response of PSCs and the cell temperature to an external agent change (light intensity, temperature, wind speed) is essential to determine the time scales and the span of temperature required in experimental measurement protocols. In this work we study the effect of realistic temperature conditions on the performance of PSCs (cell temperature and efficiency) and their transient response to environmental external changes using a theoretical-experimental combined approach. A thermal transient resistor-capacitor (RC) circuit model, previously developed and validated for silicon photovoltaic modules, is adapted to estimate the cell temperature and to simulate the transient thermal performance of the perovskite solar cell as a function of device parameters and environmental variables. This model considers absorption, convection, conduction, and radiative exchanges and it is based on the experimentally measured thermal and optical dependence of electrical parameters of PSCs, strengthening its capacities to predict and optimize the performance of this type of solar cells. We measure the current–voltage (I–V) curves as a function of the temperature and light intensities and extract its characteristic I–V parameters. By combining the experimental results with our model, we conclude that the increase of the cell temperature is strongly linked to the absorption in the perovskite layer, in the front glass and fluorine doped tin oxide FTO layer. We also analyze the annual energy yield (EY) of stable PSC modules, assuming no device degradation and working on different geographical locations, in PV farms and on rooftops to evaluate the impact of radiative exchange and air convection on the EY. We emphasize the importance of employing a comprehensive thermal model for EY estimations as it can change the results by more than 10%. The proper calculation of the cell temperature is essential not only to calculate the EY, but also as an input to predict the lifetime of the device. This work opens the possibility to optimize the device from three perspectives: optical, electrical and thermal (stability).

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

Backgound In order to reduce the treatment gap of mental disorders, the World Health Organization (WHO) has proposed the mhGAP guidelines to be implemented globally. Aim of the study To examine the effectivity of a training course based on the WHO-mhGAP guidelines to increase knowledge and readiness for identification and management of depression and suicide risk in primary care (PC) in Mexico. Methods PC clinicians were invited to participate in a traning course; before and after it, all completed an evaluation of knowledge of mhGAP and depression (0-10 points), and self-efficacy in suicide risk management (0–40 points), and were classified according to Prochaska and Diclemente transtheorical model in their particular stage of readiness for identification and management of these conditions. Results The sample included 60 health professionals. Before training, clinicians had adequate knowledge of depression and its treatment (8.1 ± 1.66), but not on the mhGAP model and/or suicide risk management, which increased by the end of training (mhGAPpre:7.91 ± 2.19 vs. mhGAPpost:8.77 ± 1.34, p = 0.01; SuicidePRE:29.16 ± 9.35 vs. SuicidePOST:39.24 ± 6.83, p = 0.0001). Before training, most clinicians were at the contemplation stage (42.6% vs. 37.7% at the action and 19.7% at the precontemplation stage). By the end of the training, a decrease in the number of clinicians at both the contemplation and precontemplation stages (to 36.1% and to zero, respectively) and a significant increase of clinicians at the action stage (to 63.9%) was observed. Conclusions: A training course based on the WHO-mhGAP could be an effective tool for increasing PC clinicians’ willingness to implement mental health services.

Introduction: Macrophages containing exogenous pigments are commonly encountered in cytological specimens. Case Presentation: We present a case of tumor tattooing as an infrequent exogenous source of peritoneal fluid macrophagic pigment in a 76-year-old female. Discussion and Conclusion: Tattooing-derived ink can be a source of macrophagic pigment and should not be confused with other endogenous or exogenous pigments. The anatomical location and past medical history of the patient can aid in the diagnosis.

Objective To evaluate azilsartan medoxomil (AZM) (Edarbi®) utilization patterns in the primary-care setting in Germany. Materials and methods This is a retrospective cohort study among patients receiving AZM in the primary-care setting in Germany. Prescription patterns - including patient demographics, off-label use, use in specific populations, concomitant use of other antihypertensive drugs, and drugs potentially causing interactions with AZM - were analyzed in two periods (01/2012 - 12/2013 and 01/2014 - 11/2016) using the primary-care physician panel of German IMS® Disease Analyzer, a patient-level electronic medical records database. Results In total, 852 of 1,159 (74%) and 696 of 811 (86%) patients met the inclusion criteria for both periods, respectively. Approximately 25% of patients were aged ≥ 75 years; 1 patient was l 18 years old; ~ 50% were females. AZM was prescribed for the approved indication of essential hypertension in 83% and 68% of patients in the first and second period, while indication was missing in 12% and 26% of patients, respectively. AZM was coprescribed on the same day with other antihypertensive drugs in 23% (first period) and 37% (second period) of patients. Drugs that might cause an interaction with AZM were coprescribed on the same day in 3% of patients in both periods; overlapping prescription periods were detected in 14% (first period) and 8% (second period) of patients. Coprescription of AZM with angiotensin-converting enzyme (ACE) inhibitors (2%) or aliskiren (l 1%) on the same day was rare in both periods. Overlapping prescription periods with AZM decreased from 20 to 6% for ACE inhibitors and from 8 to 1% for aliskiren. Conclusion Findings from this real-world evidence study demonstrate that AZM was generally utilized for approved indication and in accordance with the summary of product characteristics recommendations. .

Dyslipidaemia plays a major role in the pathogenesis of atherosclerosis. Every year, scientific institutions publish cardiovascular prevention guidelines with updated goals and recommendations based on new evidence. However, medical barriers exist that make achieving these goals difficult and gaps between guidelines and best daily clinical practice still persist. The International Society of Cardiovascular Pharmacotherapy designed the Surveillance of Prescription Drugs in the Real World Project (VIPFARMA ISCP), a survey for physicians who manage lipid disorders in high-risk patients. Seven clusters of questions will be analysed comprising demographics, institution profile, access to continuing medical education, clinical practice profile, attitude regarding use of statins, knowledge regarding proprotein convertase subtilisin/kexin type 9 inhibitors and attitudes regarding medical decisions about triglycerides. The present study will be the first part of a larger programme and aims to shed light on barriers between lipid-lowering drug therapy recommendations in the 2019 European Society of Cardiology guidelines and clinical practice in different countries.

Background The COVID-19 pandemic's mental health consequences remain unknown. Aim to assess the mental health status of ambulatory cardiometabolic patients during COVID-19 pandemic lockdown in Spanish speaking Latin American countries. Methods Cardiometabolic patients without COVID-19 evidence in 13 Latin American countries answered a survey between June 15th and July 15th, 2020. The Diagnosis Manual of Mental Disorders fifth edition was used to identify the presence of major depressive symptoms. Results The sample included 4,216 patients, 1,590 (37•71%; IC95% 36•24-39•19) were considered suffering major depression. Female gender, consuming ≥ 5 medications day, physical activity < 100 minutes weekly, low fruits and vegetables intake, poor treatment adherence, reduced food consumption were independently associated to the presence of major depressive symptoms. Conclusions The CorCOVID Latam Psy study showed that one third of the Latin American Spanish speaking population is suffering from major depressive symptoms during the COVID-19 outbreak.

The significant expansion and transformation of private label brands (PLBs) in many categories and markets worldwide have dramatically modified the competitive reality of the marketplace resulting in a new configuration of the brand landscape. This phenomenon has also contributed to the emergence of divergent brand choice patterns among consumers. By segmenting brand buyers on the basis of their brand choice behavior and psychographics, specifically lifestyles, we uncover four consumer segments purchasing different mixes of brand typologies, namely, top-tier and second-tier manufacturer brands as well as PLBs. Each segment exhibits different motives underlying its brand choice pattern. Identifying these diverse and unique brand choice patterns and the drivers of them has meaningful strategic implications for retail managers on how to incentivize PLB choice and for manufacturer brand managers on how to combat PLB growth. Finally, we discuss how the identification of consumer segments exhibiting distinct brand purchase patterns may have implications for the future of brands and brand management.

Conflicts between national and local governments over land use in floodplains have been well documented in the US and elsewhere. The US National Flood Insurance Program offers subsidized flood insurance to communities that agree to prevent further development in floodplains, but the requirements are poorly enforced and local governments are commonly reluctant to restrain development on flood-prone lands. In this paper we highlight this problem in particularly sensitive areas: the floodways (or flood bypasses) that are essential components of the Mississippi River flood control system. To properly operate the flood control system, the US Army Corps of Engineers must be able to divert flow from the mainstem Mississippi into the bypasses, thereby lowering stage in the main river, and thus minimizing flooding of cities and other vulnerable areas. However, operation of the Birds-Point-New Madrid Floodway in Missouri was compromised in 2011 by local opposition (and a legal challenge ultimately rejected by the US Supreme Court), and it was finally used to accommodate floodwaters. The West Atchafalaya Floodway in Louisiana experienced a threefold increase in the number of structures within the floodway from about 1970 to 2010. Because of the pattern of flooding, the West Atchafalaya Floodway was not needed in 2011, but if it is needed in the future, its operation may be compromised by the extensive encroachments within the floodway. Thus, operation of critical national infrastructure, designed to deal with floods on an interstate, river-basin scale, is compromised by land-use decisions made at the local level.

(c) 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/, http://www.sciencedirect.com/science/article/pii/S1566119917302434, Organic solar cells (OSCs) are promising photovoltaic devices to convert solar energy into electrical energy. Their many advantages such as lightweight, flexibility and low manufacturing costs are intrinsic to the organic/polymeric technology. However, because the performance of OSCs is still not competitive with inorganic solar cells, there is urgent need to improve the device performance using better designs, technologies and models. In this work, we focus on the developing an accurate physics-based model that relates the charge carrier density at the metal-organic boundaries with the current density in OSCs using our previous studies on single-carrier and bipolar diodes. The model for the boundary condition of the charge carrier density at the interfaces of OSCs follows a power-law function with the current density, both in dark and under illumination, and simulated current-voltage characteristics are verified with experimental results. The numerical simulations of the current-voltage characteristics of OSCs consider well-established models for the main physical and optical processes that take place in the device: light absorption and generation of excitons, dissociation of excitons into free charge carriers, charge transport, recombination and injection-extraction of free carriers. Our analysis provides important insights on the influence of the metal-organic interfaces on the overall performance of OSCs. The model is also used to explain the anomalous S-shape current-voltage curves found in some experimental data., This work was supported by Ministerio de Educación y Ciencia under research Grant FPU12/02712 and MINECO/FEDER under research Project MAT2016-76892-C3-3-R, and the Canada Research Chair program, NSERC ResEau strategic network and the NCE IC-IMPACTS.

(c) 2017 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works., http://ieeexplore.ieee.org/document/7907234/, Using 70nm thick spin-coated film of newly synthesized octadecyl substituted copper tetrabenzotriazaporphyrin (10CuTBTAP) as an active layer on a highly doped silicon (110) gate electrode substrates, output characteristics and transfer characteristics of bottom-gate bottom-contact organic thin film transistors have been measured at room temperature. A compact model for thin film transistors has been employed as a part of circuit design tool to extract device parameters such as the charge carrier mobility, the threshold voltage and the contact resistances. Parallel measurements and analysis were performed on similarly constructed devices with a copper phthalocyanine analogue (10CuPc). The results reveal that the 10CuPc layer is relatively more susceptible to trapping degradation near the gate region than a 10CuTBTAP layer, which is significant in order to achieve stability in these transistors. The application of the simple square law in the classical MOS model provides a quicker but approximate interpretation of the transistor performance without providing information on the gate voltage dependence of mobility and the effects of the contact regions. In this comparative study, the analysis of the contact regions is found to be very important for determining the difference in the performance of two transistors., This work was partially supported by Ministerio de Educación y Ciencia under research Grant FPU12/02712 and MINECO under research Project MAT2016-76892-C3-3-R. Experimental work was carried out at Queen Mary, University of London under financial support from the UK Technology Strategy Board (Project No: TP/6/EPH/6/S/K2536J).

This study aimed to examine how loneliness contributes to metabolic dysregulation among older adults with depression and determine the relative contribution of loneliness to the development of chronic diseases in late adulthood. Harmonised data from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project were used. Concretely, the sample comprised 6195 participants (53.95% women; M = 61.30 years, SD = 7.11) from three European cohorts. Three groups were considered: control group (CG); depressive symptom episode group (DEP); and a group with depression and loneliness (DEP + LONE). A metabolic score was estimated using anthropometric and blood indicators, by means of multi-indicator multi-causes (MIMIC) modelling and after controlling for sociodemographic and health-related covariates. Group-comparison was based on measurement-invariance procedures. Multimorbidity development was predicted at follow-up considering the study group and relevant covariates. All the analyses were sex-specific. As a result, measurement invariance revealed the influence of group (ΔCFI = −0.017 for male participants and ΔCFI = −0.009 for female ones) on metabolic scores in both sexes. Metabolic scores were significantly lower (i.e., they had more metabolic risk) in DEP + LONE women in comparison to women from the other groups. DEP men showed the lowest metabolic scores but those from the DEP + LONE group showed meaningfully lower scores than CG men (d = 1.35). In terms of multimorbidity prediction, DEP + LONE group membership significantly predicted the outcome in both sexes; DEP group membership significantly predicted multimorbidity at follow-up in women. In summary, these results highlight the relevant contribution of loneliness in depression-related metabolic dysregulation in the short- (concurrent metabolic risk) and long-term (chronic condition development). Moreover, sex-specific mechanisms seem to be involved in metabolic alterations of depressed people showing loneliness feelings. This study calls for action to reduce the impact of loneliness in old age and to promote healthy ageing.

Bipolar disorder and major depression are associated with significant disability, morbidity, and reduced life expectancy. People with mood disorders have shown higher ratios of unhealthy lifestyle choices, including poor diet quality and suboptimal nutrition. Diet and nutrition impact on brain /mental health, but cognitive outcomes have been less researched in psychiatric disorders. Neurocognitive dysfunction is a major driver of social dysfunction and a therapeutic target in mood disorders, although effective cognitive-enhancers are currently lacking. This narrative review aimed to assess the potential cognitive benefits of dietary and nutritional interventions in subjects diagnosed with mood disorders. Eight clinical trials with nutrients were identified, whereas none involved dietary interventions. Efficacy to improve select cognitive deficits has been reported, but results are either preliminary or inconsistent. Methodological recommendations for future cognition trials in the field are advanced. Current evidence and future views are discussed from the perspectives of precision medicine, clinical staging, and nutritional psychiatry. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Background The Emerald project's focus is on how to strengthen mental health systems in six low- and middle-income countries (LMICs) (Ethiopia, India, Nepal, Nigeria, South Africa and Uganda). This was done by generating evidence and capacity to enhance health system performance in delivering mental healthcare. A common problem in scaling-up interventions and strengthening mental health programmes in LMICs is how to transfer research evidence, such as the data collected in the Emerald project, into practice. Aims To describe how core elements of Emerald were implemented and aligned with the ultimate goal of strengthening mental health systems, as well as their short-term impact on practices, policies and programmes in the six partner countries. Method We focused on the involvement of policy planners, managers, patients and carers. Results Over 5 years of collaboration, the Emerald consortium has provided evidence and tools for the improvement of mental healthcare in the six LMICs involved in the project. We found that the knowledge transfer efforts had an impact on mental health service delivery and policy planning at the sites and countries involved in the project. Conclusions This approach may be valid beyond the mental health context, and may be effective for any initiative that aims at implementing evidence-based health policies for health system strengthening.

This work investigates the band offset influence at the MAPbI 3 /SnO 2 interface by an electronic-ionic drift-diffusion model with an emphasis on utilizing realistic band offset values. We validate the model by comparison with experimental measurements and discuss the effect of different concentrations of fast positive and slow negative ions in the perovskite layer. Band offset < 0.1 eV at the perovskite/electron transport layer interface is proposed to allow ideal carrier transport with negligible hysteresis, regardless of the presence of mobile ions. Reducing the band offset thus stands out as a more feasible way to optimize the performance of perovskite and perovskite/silicon-based tandem solar cells.

Please cite this article as: A. Romero, C. Jiménez, J. González, P. López-Varo, M.J. Deen, J.A. Jiménez-Tejada, Compact modeling of the effects of illumination on the contact region of organic phototransistors, Organic Electronics, (2019), 70, 113-121., A good modeling of degrading effects in an electronic device, such as the contact region of organic phototransistors (OPTs), can be favorably used to better describe and optimize the performance of the whole device. Furthermore, a proper design of the contacts can enhance the exciton dissociation and the extraction of photogenerated charge in the device. In this work, a compact model for OPTs is developed. This model is valid for all the operation regimes of the transistors. It includes a model for the contact region of the device that incorporates the effects of illumination. The compact model and the contact region model are validated with published experimental data from several OPTs under different illumination conditions. The tool used to validate the model is an evolutionary parameter extraction procedure developed in a previous work. The results show that both photoconductive and photovoltaic effects impact the intrinsic region of the transistor, as well as the electrical behavior of the contact region. The parameters used in the contact region model are linked to these photovoltaic and photoconductive effects., This work was supported by projects MAT2016-76892-C3-3-R and TIN2015-67020-P funded by the Spanish Government and European Regional Development Funds (ERDF) and by “Beca de Iniciación a la Investigación para estudiantes de Grado” given by the University of Granada.

Background: BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine (PEI), that acts as an agonist to toll-like receptor 3 and targets the cytosolic helicase melanoma differentiation-associated gene 5 and retinoic acid-inducible gene I. By mimicking the effect of a viral infection, it mobilizes the immune system, including activation of dendritic cells, CD8 T-cell infiltration, induction of interferons (IFNs), induction of apoptosis and enhancement of immunogenic cell death. Clinical data are available from the first-in-human study (NCT02828098) which evaluated single intratumoral (IT) BO-112 (Part 1; N = 16) and the combination of IT BO-112 with pembrolizumab or nivolumab (Part 2; N = 28). Part 2 showed an ORR of 11% and DCR of 46% in patients with multiple tumor types. Of them, 2 out of 10 (20%) patients with melanoma resistant to anti PD-1 achieved a partial response. Safety profile of BO-112, both as single agent and in combination with anti-PD-1, is manageable and currently characterized by Grade 1 fever and other flu-like symptoms. A phase 2 clinical study of IT BO-112 in combination with pembrolizumab in patients with liver metastases from colorectal or gastric/gastro-esophageal junction cancer patients is currently ongoing. Methods: Phase 2, single arm, open label study of IT BO-112 in combination with pembrolizumab in patients with advanced and/or metastatic melanoma that have progressed on anti-PD-1-containing treatment (NCT04570332). BO-112 will be administered once weekly (QW) in 1 to 8 tumor lesions, total dose 1-2 mg (depending on the number of injected lesions), for the first 7 weeks and then once every three weeks (Q3W); pembrolizumab 200 mg will be administered Q3W. Key eligibility criteria include histologically confirmed, unresectable cutaneous or mucosal melanoma with known BRAF status. Patients must have progressed on or after treatment with an anti-PD-1/L1 mAb. At least one lesion RECIST 1.1 measurable and amenable for weekly IT injection is needed. Primary efficacy variable is ORR by RECIST 1.1, assessed by independent central radiologist (by QUIBIM Precision platform). Secondary efficacy variables include clinical activity in terms of DCR, DOR, PFS, OS, iRECIST, safety and PKs. Exploratory objectives include itRECIST and evaluation of tumor microenvironment (by Pangaea laboratory). A 1-sided alpha of 4.19% and power of 81.8% are used. A total of 40 patients will be enrolled. If less than 8 patients out of 40 have ORR, the study will not meet the statistical bar. Study was approved on 14 December in Spain; enrollment is open; two sites are active as of 18 December 2020. Nineteen sites (12 in Spain and 7 in France) are planned to be activated. Citation Format: Iván Márquez-Rodas, Miguel Fernández de Sanmamed Gutiérrez, María González Cao, Ana M. Arance, Alfonso Berrocal, Eduardo Castañon, Sofía España, Pablo Cerezuela-Fuentes, Juan F. Rodríguez-Moreno, Pilar López Criado, Juana Oramas, Luis de la Cruz Merino, Stéphane Dalle, Caroline Dutriaux, Julie Charles, Caroline Robert, Brigitte Dréno, Henri Montaudié, Philippe Saiag, Javier Sánchez-López, María Rojas, Helena Escuin-Ordinas, Vanesa Pons Sanz, Sonia Maciá, Marisol Quintero. Phase 2 clinical study to evaluate the efficacy and safety of intratumoral BO-112 in combination with pembrolizumab in patients with advanced melanoma that have progressive disease on anti-PD-1-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT233.

Here we investigate the impact of four different metal back contacts on the photovoltaic (PV) performance of Co3O4 thin film all-oxide photovoltaic cells. A combinatorial TiO2|Co3O4 heterojunction thin film device library was made with thickness gradients for both metal oxide layers. Grids of four different metal back contacts were then deposited on top of these layers. A significant effect of the metal back contacts on the final photoconversion performance has been observed by combinatorial PV measurements. We analyze these results via advanced numerical simulations and different scenarios in order to explain the recombination mechanisms at the different back contacts. We conclude that the nature of the back contact material controls the density of surface states and, therefore, the undesirable surface recombination at the absorber–back contact interface. This project has received funding from the European Union’s Seventh Programme for research, technological development and demonstration under grant agreement No 309018. Funding from the European Union Seventh Framework Program [FP7/2007-2013] under grant agreement 316494 is also acknowledged.

International audience; Perovskite/silicon tandem modules have recently attracted growing interest as a potential candidate for new generations of solar modules. Combined with a bifacial configuration it can lead to considerable energy yield improvement in comparison to conventional monofacial tandem solar modules. Optical modeling is crucial to analyze the optical losses of perovskite/silicon solar modules and achieve efficient light management. In this article we study the optical properties of four-terminal bifacial tandem modules, using metal-halide perovskite top solar cell and a conventional industrial crystalline silicon PERC bottom solar cell. We propose a method to analyze bifacial gains, improve back side light management and challenge it under realistic spectral conditions at several locations with various albedos. We show that both optimized designs for the back side show comparable advantages at all locations. These results are a good sign for the standardization of bifacial four-terminal perovskite/silicon modules.

Background: The COVID-19 pandemic has produced devastating effects on the health care system, also affecting cancer patient care. When the pandemic reached Spain by the end of February 2020, the scarce data about COVID-19 infection in cancer patients pointed out a higher risk of complications due to cancer diagnosis and also to cancer therapies. These conjectures led to concerns about hospital follow-up and cancer therapies of cancer patients. More recent studies have included a higher number of patients, but heterogeneous according to cancer type and tumor stage, with few melanoma patients recorded. Given that different tumor types are associated with specific comorbidities that have a known impact on COVID-19 evolution, analysis of COVID-19 by cancer types is mandatory. Similarly, analysis by tumor stage is relevant, as advanced cases could have different responses to viral infection due to tumor-related immunosuppression and general condition deterioration. Methods: In Spain we have completed a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020 to June 8th, 2020. Patients with a previous diagnosis of melanoma, presenting with Sars-Cov-2 infection to our network of hospitals, were eligible for enrollment. A prospective observational study with a case registry followed by a retrospective analysis of patient data has been performed. Results: 64 patients have been included. Median age is 68 years (range 6 to 95 years), 22 (34%) patients are females, and 35 (55%) patients have stage IV melanoma. Twenty-one (33%) patients were on active anticancer treatment with anti PD-1 antibodies, 19 (30%) patients with BRAF plus MEK inhibitors, and 24 (37%) patients were not on active treatment. Asymptomatic/paucisymptomatic evolution was recorded in 19 (30%) patients and mild severity in 13 (20%) patients, not requiring hospital admission by COVID-19. Serious and life-threatening complications were recorded in 18 (28%) and 14 (22%) patients, respectively, including 28 (44%) patients who required oxygen therapy and 3 (5%) patients who had ICU admission. COVID-19 episode is resolved in 55 cases, including 34 (53%) patients cured, eight (12%) patients who have died due to melanoma progression, and 13 (20%) patients due to COVID-19. The median age of patients who died from COVID-19 was 74 years (range 49 to 91), while for those cured it was 64 years (range 6 to 95); 85% of patients who died were males, while this rate decreased to 62% for those cured. The mortality rate from COVID-19 was 20% for both stage IV and localized melanoma, while according to melanoma treatment it was 21%, 16%, and 21% for immunotherapy, BRAF plus MEK inhibitors, and for those who were not undergoing active cancer treatment, respectively. Conclusion: Our results show that the risk of death in melanoma patients is higher in males and older patients, and it is similar according to tumor stage and melanoma therapy. The impact of cancer diagnosis and treatments on COVID-19 evolution is lower than previously expected. Citation Format: Maria Gonzalez-Cao, Cristina Carrera, Juan Francisco Rodriguez Moreno, Pedro Rodriguez-Jiménez, Mónica Antoñanzas Basa, Marta Feito Rodríguez, Teresa Puertolas, Eva Muñoz, José Luis Manzano, Ivan Marquez-Rodas, Juan Martín-Liberal, Ainara Soria, Pilar Lopez Criado, Almudena García Castaño, Aram Boada, Pablo Ayala de Miguel, Susana Puig, Guillermo Crespo, Pablo Luna Fra, Cristina Aguayo Zamora, Jesús Gardeazabal, Cayetana Maldonado Seral, Ana Drozdowskyj, Mariano Provencio, Alfonso Berrocal. COVID-19 in melanoma patients: Spanish register [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-059.

Late-life depression is a highly prevalent mental health condition with devastating consequences even from its earliest stages. Alterations in physiological functions, such as inflammatory and metabolic, have been described in patients with depression. However, little is known on the association between depression symptom course and metabolic and inflammation dysregulation. This study aimed to depict the course of depression symptoms while ageing, taking into consideration inter-individual heterogeneity. Moreover, it intended to study the associations between inflammatory and metabolic risk profiles and symptom trajectories. To do so, data from 13,203 adults aged 50–90 years (52.75% women; mean age at baseline = 65.07, SD = 10.00) were used. Blood sample and blood pressure measures were taken from 1536 participants (56.58% women; mean age at baseline = 61.73 years, sd = 7.64). Depression symptoms were assessed every two years across a 10-year follow-up. Trajectories were identified by means of latent class mixed modelling. Inflammation and metabolic risk profile scores were obtained from plasma and diagnostic-based indicators in the follow-up, using a robust latent-factor approach. Multigroup modelling was used to study the associations between the profiles and symptom trajectories. As a result, three heterogeneous trajectories of symptoms were identified (low-symptom, moderate-symptom and high-symptom trajectory). Participants depicting a high-symptom trajectory showed the greatest inflammation profile score and high metabolic risk. Moderate-symptom trajectory was also related to high inflammation and metabolic risk. To sum up, at-risk trajectories of symptoms were associated with high inflammation and risk of metabolic diseases. This study provides valuable evidence to advance personalised medicine and mental health precision, considering person-specific profiles and physiological concomitants.

Background Although mental illness accounts for only 4% of aggressive behavior in the general population, there remains a modest association between aggressive behavior and psychotic disorders, particularly in the early stages of the illness. However, little is known about the specific factors associated to this increased risk. Aims The present study aims to assess the rates, characteristics and risk factors of aggressive behavior in first episode psychosis patients (FEP). Method We conducted a retrospective chart review of 449 FEP patients recruited from an outpatient early psychosis clinic. Aggressive behavior and clinical information were rated based upon information gathered from the chart review of data collected at baseline and after 6 months of follow-up. Results Rates of aggressive behavior were 54.3% in FEP patients. Aggressive behavior was significantly associated with higher rates of history of birth complications, neurodevelopmental delays, learning difficulties, alcohol use disorders, and the clinical domain of poverty symptoms. In addition to aggressive behavior, 16.7% of FEP patients exhibited suicidal ideation or behaviors and 11.4% exhibited non-suicidal self-injurious behavior (NSSIB). In contrast to baseline, aggressive behaviors at 6 months follow up were almost entirely absent. Conclusions Patients at early stages of psychosis have high rates of aggressive and suicidal behavior prior to contact with clinical services. Neurodevelopmental adversities, alcohol use disorders and poverty symptoms are associated to higher risk of aggression in early psychosis. Participation in early psychosis specialty care resulted in a dramatic reduction in aggressive behavior.

Background: Eosinophilic esophagitis (EoE) was first described in the 1990s, showing an increasing incidence and prevalence since then, being the leading cause of food impaction and the major cause of dysphagia. Probably, in a few years, EoE may no longer be considered a rare disease. Methods: This article discusses new aspects of the pathogenesis, symptoms, diagnosis, and treatment of EoE according to the last published guidelines. Results: The epidemiological studies indicate a multifactorial origin for EoE, where environmental and genetic factors take part. EoE affects both children and adults and it is frequently associated with atopic disease and IgE-mediated food allergies. In patients undergoing oral immunotherapy for desensitization from IgE-mediated food allergy the risk of developing EoE is 2.72%. Barrier dysfunction and T-helper 2 inflammation is considered to be pathogenetically important factors. There are different patterns of clinical presentation varying with age and can be masked by adaptation habits. Besides, symptoms do not usually correlate with histologic disease activity. The diagnostic criteria for EoE has evolved but mainly requires symptoms of esophageal dysfunction with histologic evidence of a peak value of at least 15 eosinophils per high-power field. Endoscopies have to be repeated in order to diagnose, monitor, and treat EoE. Treatment of EoE can be started either by drugs (PPIs and topical corticosteroids) or elimination diets. The multistage step-up elimination diet management approach of EoE is promising. Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment. Conclusions: Research in recent years has contributed to a better understanding of EoE's pathogenesis, genetic background, natural history, allergy workup, standardization in assessment of disease activity, evaluation of minimally invasive diagnostic tools, and new therapeutic approaches. However, several unmet needs are to be solved urgently, as finding a non-invasive disease-monitoring methods and biomarkers for routine practice, the development or new therapies, novel food allergy testing to detect triggering foods, drug, and doses required for initial therapy and safety issues with long-term maintenance therapy, amongst others. Besides, multidisciplinary management units of EoE, involving gastroenterologists, pediatricians, allergists, pathologists, dietitians, and ENT specialists are needed.

Please cite this article as: J. A. Jiménez Tejada, P. Lopez-Varo, N. B. Chaure, I. Chambrier, A. N. Cammidge, M. J. Cook, A. Jafari-Fini, and A. K. Ray, Organic thin film transistors using a liquid crystalline palladium phthalocyanine as active layer, Journal of Applied Physics 123, 115501 (2018), 70 nm thick solution-processed films of a palladium phthalocyanine (PdPc_6) derivative bearing eight hexyl (–C_6H_13) chains at non-peripheral positions have been employed as active layers in the fabrication of bottom-gate bottom-contact organic thin film transistors (OTFTs) deposited on highly doped p-type Si (110) substrates with SiO_2 gate dielectric. The dependence of the transistor electrical performance upon the mesophase behavior of the PdPc_6 films has been investigated by measuring the output and transfer characteristics of the OTFT having its active layer ex situ vacuum annealed at temperatures between 500 ºC and 200 ºC. A clear correlation between the annealing temperature and the threshold voltage and carrier mobility of the transistors, and the transition temperatures extracted from the differential scanning calorimetric curves for bulk materials has been established. This direct relation has been obtained by means of a compact electrical model in which the contact effects are taken into account. The precise determination of the contact-voltage drain-current curves allows for obtaining such a relation., This work was partially supported by MINECO of Spain under research Project MAT2016-76892-C3-3-R. Experimental work was carried out at Queen Mary, University of London under financial support from the UK Technology Strategy Board (Project No. TP/6/EPH/6/S/K2536J).

Based on many clinical and preclinical findings the ‘vigilance regulation model of mania’ postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605). The work was supported by a grant of the Spanish ‘Ministerio de Sanidad, Politica Social e Igualdad’ (Ministry of Health, Social Politics and Equality), EC10-110, EC10-297, EC10-333 and EC10-064, and by the Instituto de Salud Carlos III of Spain (CIBERSAM), grant 11INT2 which had been provided after a peer review process. The funding source had no rule in the study design, in the collection, analysis and interpretation of data, in the writing of the manuscript and in the decision to submit the paper for publication.

A compact model for the current-voltage characteristics of organic thin-film transistors (OTFTs), which includes the effects of the contact regions, is proposed. Different physical and morphological aspects of contacts with organic or other emerging materials such as graphene, semiconducting dichalcogenides such as MoS2, or NW devices are described. The electrical behavior of the contacts is studied in OTFTs, and circuit models that describe them are reviewed. Two trends are observed in the current-voltage curves of the contacts of different OTFTs: linear and nonlinear, and different models are used to explain them. A unified model for the contact region that reproduces both trends and gathers the different physical and structural features of the contacts is developed. It is described by a single parameter and introduced in a generic analytical model for TFTs. The variability in OTFT structures, materials, and fabrication approaches gives rise to a strong variability in the values of the parameters of the model. In this regard, a characterization technique to determine the value of the parameters of the model from experimental data is also developed. Different physical tests are proposed to validate the results of the technique. The procedure is applied to recent experimental data for different pentacene-based transistors. The good agreement between the experimental data and our analytical results provides a way to relate the parameters of the model with the physical or geometrical origin of the contact effects in OTFTs.

The objective of the described research effort was to identify a novel serotonin and norepinephrine reuptake inhibitor (SNRI) with improved norepinephrine transporter activity and acceptable metabolic stability and exhibiting minimal drug-drug interaction. We describe herein the discovery of a series of 3-substituted pyrrolidines, exemplified by compound 1. Compound 1 is a selective SNRI in vitro and in vivo, has favorable ADME properties, and retains inhibitory activity in the formalin model of pain behavior. Compound 1 thus represents a potential new probe to explore utility of SNRIs in central nervous system disorders, including chronic pain conditions.

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

López Varo, Pilar et al., Solar energy conversion using semiconductors to fabricate photovoltaic devices relies on efficient light absorption, charge separation of electron-hole pair carriers or excitons, and fast transport and charge extraction to counter recombination processes. Ferroelectric materials are able to host a permanent electrical polarization which provides control over electrical field distribution in bulk and interfacial regions. In this review, we provide a critical overview of the physical principles and mechanisms of solar energy conversion using ferroelectric semiconductors and contact layers, as well as the main achievements reported so far. In a ferroelectric semiconductor film with ideal contacts, the polarization charge would be totally screened by the metal layers and no charge collection field would exist. However, real materials show a depolarization field, smooth termination of polarization, and interfacial energy barriers that do provide the control of interface and bulk electric field by switchable spontaneous polarization. We explore different phenomena as the polarization-modulated Schottky-like barriers at metal/ferroelectric interfaces, depolarization fields, vacancy migration, and the switchable rectifying behavior of ferroelectric thin films. Using a basic physical model of a solar cell, our analysis provides a general picture of the influence of ferroelectric effects on the actual power conversion efficiency of the solar cell device, and we are able to assess whether these effects or their combinations are beneficial or counterproductive. We describe in detail the bulk photovoltaic effect and the contact layers that modify the built-in field and the charge injection and separation in bulk heterojunction organic cells as well as in photocatalytic and water splitting devices. We also review the dominant families of ferroelectric materials that have been most extensively investigated and have provided the best photovoltaic performance., The research leading to these results has received funding from the European Union Seventh Framework Program [FP7/2007–2013] under grant agreement 316494 and from MINECO of Spain under project TEC2013-47283-R and Grant FPU12/02712. F.R. acknowledges funding and partial salary support for work on multiferroic materials from NSERC, through an EWR Steacie Memorial Fellowship.

PurposeThe aim of this paper is to provide evidence that private label brands (PLB) have the ability to build brand equity as they develop, and to determine whether the capitalization of PLB equity varies across consumer segments and product categories. The paper builds on previous research incorporating consumer‐level factors, showing their relevance as key determinants of PLB choice.Design/methodology/approachThe brand choice model used is a multinomial logit model (MNL) calibrated with a consumer panel database of two product lines of yoghurt from 8,000 Spanish households for a three‐year period.FindingsIt is shown that PLB have been able to build brand equity throughout their development, across product categories; however, brand equity is capitalized across only some consumer segments. The use of consumer‐level factors to segment the market prior to measuring brand equity is necessary to allow the identification of consumer groups where equity is created.Practical implicationsFindings provide key directions to PLB managers regarding how to determine, approach and leverage the equity of their PLB across different consumer segments and product categories.Originality/valuePrior research has attempted to measure PLB equity using product/brand factors and market factors, but without considering consumer‐level factors. In this research, consumer‐level factors, specifically consumer demographics, are incorporated into the analysis, and equity is measured across seven different consumer segments for two product lines.

PurposeThe purpose of this paper is to analyse whether private label brands (PLB) have been able to build brand equity throughout their development. Specifically, it aims to develop and test a measurement model that measures PLB brand equity across product lines.Design/methodology/approachA brand choice model is developed using a multinomial logit model and it is calibrated using a consumer panel database of two product lines of yoghurt from 8,000 Spanish households for a three‐year period.FindingsPrior research has considered PLB as the unbranded alternative to manufacturer brands. In this research empirical evidence is provided that PLB have built brand equity throughout their development and that this equity varies across the different PLB offered in the market, and across product lines.Practical implicationsThese findings offer valuable insights to retailers on how to manage PLB and to manufacturers on how to approach and compete against them.Originality/valueThe vast majority of academic research has not approached the PLB phenomenon from a branding perspective. This research constitutes a first attempt to measure brand equity on PLB. It measures PLB brand equity for each typology of PLB in the market.

The poor performance of the Colombian economy in the world markets during the late nineteenth and early twentieth centuries are attributable, in part, to the weakness of settlers’ property rights in frontier lands. To examine this issue, we collected data on production of agricultural exports at county (municipal) level in 1892, coffee production in 1925, and of public land allocation and land conflicts during the nineteenth and twentieth centuries. The quantitative analysis suggests that in the absence of land conflicts, the per capita production of agricultural exports would have been in 1925 at least twice as much as that observed.

Background Guidelines for noninvasive mechanical ventilation (NIMV) recommend continuous positive airway pressure in patients with thoracic trauma who remain hypoxic despite regional anesthesia. This recommendation is rated only by level C evidence because randomized controlled trials in this specific population are lacking. Our aim was to determine whether NIMV reduces intubation in severe trauma-related hypoxemia. Methods This was a single-center randomized clinical trial in a nine-bed ICU of a level I trauma hospital. Inclusion criteria were patients with Pa o 2/F io 2 8 h while receiving oxygen by high-flow mask within the first 48 h after thoracic trauma. Patients were randomized to remain on high-flow oxygen mask or to receive NIMV. The interface was selected based on the associated injuries. Thoracic anesthesia was universally supplied unless contraindicated. The primary end point was intubation; secondary end points included length of hospital stay and survival. Statistical analysis was based on multivariate analysis. Results After 25 patients were enrolled in each group, the trial was prematurely stopped for efficacy because the intubation rate was much higher in controls than in NIMV patients (10 [40%] vs 3 [12%], P = .02). Multivariate analysis adjusted for age, gender, chronic heart failure, and Acute Physiology and Chronic Health Evaluation II at admission revealed NIMV as the only variable independently related to intubation (odds ratio, 0.12; 95% CI, 0.02–0.61; P = .01). Length of hospital stay was shorter in NIMV patients (14 vs 21 days P = .001), but no differences were observed in survival or other secondary end points. Conclusion NIMV reduced intubation compared with oxygen therapy in severe thoracic trauma-related hypoxemia. Trial registration clinicaltrials.gov ; identifier: NCT 00557752 .

Economic crises can cause adverse health effects, such as an increase in the prevalence of mental disorders and suicide rates. Nevertheless, these effects might vary across countries. While some countries successfully decouple economic crises from adverse mental health outcomes, in others the suicide rates increase due to economic crises. The differential impact of the economic crises on suicide may depend on some of the policies taken to tackle the financial downturn. Some of the mechanisms that underlay the association between suicide and economic crisis are increased unemployment, job insecurity, decreased earnings, personal debt and sudden bankruptcy. Several measures can be taken in order to prevent or decrease the negative effects of economic downturns on suicide, such as reducing the barriers to accessing health care, improving the quality of treatment of mental disorders with special attention to depression, raising the price of spirits, providing support to tackle financial problems, investing in labour market programmes and encouraging social support.

Atlas-based segmentation of MR brain images typically uses a single atlas (e.g., MNI Colin27) for region identification. Normal individual variations in human brain structures present a significant challenge for atlas selection. Previous researches mainly focused on how to create a specific template for different requirements (e.g., for a certain population). We address atlas selection with a different approach: instead of choosing a fixed brain atlas, we use a family of brain templates for atlas-based segmentation. For each subject and each region, the template selection method automatically chooses the 'best' template with the highest local registration accuracy, based on normalized mutual information. The region classification performances of the template selection method and the single template method were quantified by the overlap ratios (ORs) and intraclass correlation coefficients (ICCs) between the manual tracings and the respective automated labeled results. Two groups of brain images and multiple regions of interest (ROIs), including the right anterior cingulate cortex (ACC) and several subcortical structures, were tested for both methods. We found that the template selection method produced significantly higher ORs than did the single template method across all of the 13 analyzed ROIs (two-tailed paired t-test, right ACC at t(8)=4.353, p=0.0024; right amygdala, matched paired t test t(8)>3.175, p

Back to its origins: Pochonin C was synthesized in 11 steps from the four fragments shown in the scheme. This asymmetric synthesis and the conversion of pochonin C into radicicol defines the configuration at the center bearing the chlorine atom as S. Ipc=isopenocampheyl, PG=protecting group.

The directionality of causal relationship between customer orientation and job satisfaction is unclear from previous research. Additionally, research on this topic is based on service-workers, while middle managers are ignored, although their critical role. Drawing from literature on person-situation interaction and fit theory we develop some hypothesis on middle-manager customer orientation and job satisfaction. We test this hypothesis with 535 branch managers from a commercial bank. Results confirm that customer orientation is an antecedent of job satisfaction, and job fit and customer contact time moderates this relationship.

A 50-year-old patient, a smoker, was admitted to the hospital, with a solitary scalp lump. Subcutaneous lumps of the scalp are common but usually benign; however, the painless lump in our patient turned out to be a malignant osteolytic lesion of the skull. Frontal bone was involved, and the disease had spread to the dura. Neuroimaging showed osteolytic lesions involving the axial skeleton, skull and several vertebrae. MRI showed the involvement of the second cervical vertebra, which prompted us to start treatment with dexamethasone. Since the spinal cord was not involved, Oncologists decided not to start radiotherapy treatment until we had reached the final diagnosis. A frontal bone biopsy confirmed the diagnosis of lung carcinoma. Chest X-ray did not identify the pulmonary nodule, but CT scan revealed a 1 cm peripheral, spiculated, pulmonary nodule within a pathological parenchyma (severe diffuse pulmonary emphysema).

Ipilimumab, a fully human, recombinant, monoclonal antibody to cytotoxic T-lymphocyte antigen 4 improves overall survival (OS) in previously treated and untreated metastatic melanoma. This retrospective analysis reports data gathered by a questionnaire on the demographics, outcomes, and toxicity of ipilimumab administered through an Expanded Access Program (EAP). Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for four cycles to adults with metastatic melanoma. Efficacy outcomes included complete response, partial response (PR), progressive disease, stabilized disease, and OS. EAP data were collected from EAP physicians. A subgroup analysis examined efficacy in elderly patients (≥70 years) and factors predictive of survival were identified. Of 355 requests for ipilimumab, resulting in 288 treatments, completed questionnaires were received for 153 ipilimumab recipients (median age 58 years, 57.2% men). Efficacy was evaluated in 144 patients: complete response in 1.3%, PR in 9.6%, PR with previous progression 8.4%, stabilized disease in 14.5%, and progressive disease in 66.2%. The median OS was 6.5 months (199 days); 1-year survival was 32.9%. Predictive survival factors included lymphocytes over 1000/ml (P=0.0008) and lactate dehydrogenase more than 1.5×upper limit of normal (P=0.003). Cutaneous, hepatic, and gastrointestinal toxicities were mild. In 30 patients aged more than 70 years, ipilimumab efficacy and tolerability was similar to that of the overall population. In the clinical practice setting, ipilimumab is effective and well tolerated in patients with advanced melanoma, including elderly patients, when administered at the recommended dosage. Ipilimumab improves treatment options for patients who, until recently, have had little hope of an improved prognosis.

In this work, we propose a procedure to extract information of the trapping processes that occur in organic thin film transistors (OTFTs) during hysteresis mechanisms. The procedure is based on a compact model that describes the transistor as the combination of an intrinsic transistor and the contact regions. The model is used to extract output characteristics for the intrinsic transistor from experimental measurements. It eliminates the effect of the contacts, not only from the gate-and drain-terminal voltages, but also from fundamental parameters such as the mobility and the threshold voltage. Other models that consider the contact effects in a partial way are analyzed and the results compared to those from the proposed procedure.

[Background and Aims]: Patients with acute liver failure (ALF) often die of intracranial pressure (IP) and cerebral herniation. Main contributors to increased IP are ammonia, glutamine, edema, and blood flow. The sequence of events and underlying mechanisms, as well as the temporal pattern, regional distribution, and contribution of each parameter to the progression of neurologic deterioration and IP, are unclear. We studied rats with ALF to follow the progression of changes in ammonia, glutamine, grade and type (vasogenic or cytotoxic) of edema, blood-brain barrier permeability, cerebral blood flow, and IP. We assessed whether the changes in these parameters were similar between frontal cortex and cerebellum and evaluated the presence, type, and progression of edema in 12 brain areas. [Methods]: ALF was induced by injection of galactosamine. The grade and type of edema was assessed by measuring the apparent diffusion coefficient by magnetic resonance imaging. Cerebral blood flow was measured by magnetic resonance and blood-brain barrier permeability by Evans bluealbumin extravasation. [Results]: Increased IP arises from an early increase of bloodbrain barrier permeability in certain areas (including cerebellum but not frontal cortex) followed by vasogenic edema. Ammonia and glutamine then increase progressively, leading to cytotoxic edema in many areas. Alterations in lactate and cerebral blood flow are later events that further increase IP. [Conclusions]: Different mechanisms in specific regions of the brain contribute, with different temporal patterns, to the progression of cerebral alterations and IP in ALF. © 2011 AGA Institute., Funding Supported by grants from the Ministerio Ciencia e Innovacion (SAF2008-00062 and CSD2008-00005) and from the Consellería Educación (ACOMP-2009-025, PROMETEO-2009-027, and ACOMP2010-220), and from Conselleria Sanitat, Generalitat Valenciana (AP-092/09 and AP-024-08).