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For patients with advanced cancer, early access to palliative care can have numerous psychosocial and disease management benefits. However, it can be difficult for clinicians to initiate these initial conversations about palliative care. The aim of the present study was to beta test an intervention to facilitate timely conversations about palliative care between patients and clinicians.The study reported forms one stage of a complex intervention development study following Medical Research Council guidance for developing complex interventions. Feasibility was explored from patient and clinician perspectives in an oncology outpatient setting.Sixteen patients and 18 clinicians participated. Three phases of the intervention were assessed through patient and clinician interviews. The analysis produced three themes in each phase: (i) Preparation (patient preparedness; healthcare professionals' perspectives on palliative care; administration, data and communication); (ii) STEP consultation (defining perspectives on palliative care; how palliative care fits with the current treatment plan; permission to explore future care); (iii) Outcomes (changes in perspective and approaches to coping; opening the door to future conversations; referrals and involvement of palliative services).The STEP intervention generated important early conversations about end-of-life care that may otherwise not have occurred. No patients regretted having the STEP consultation, which resulted in palliative care referrals for some. Others felt better informed about the support services available and better able to have further conversations. Participating clinicians found the structured conversation guide useful, as it acted as a prompt for areas to cover, as well as providing an explicit way to open discussion about difficult topics.

Four-Fermi quantum field theories in (2+1) dimensions lie among the simplest models in high-energy physics, the understanding of which requires a non-perturbative lattice formulation addressing their strongly-coupled fixed points. These lattice models are also relevant in condensed matter, as they offer a neat playground to explore strong correlations in the quantum anomalous Hall (QAH) effect. We give a detailed description of our multidisciplinary approach to understand the fate of the QAH phases as the four-Fermi interactions are increased, which combines strong-coupling and effective-potential techniques, unveiling a rich phase diagram with large -N Chern insulators and Lorentz breaking fermion condensates. Moreover, this toolbox can be enlarged with recent advances in quantum information science, as we show that tensor-network algorithms based on projected entangled pairs can be used to improve our understanding of the strong-coupling limit. We also present a detailed scheme that uses ultra-cold atoms in optical lattices with synthetic spin- orbit coupling to build quantum simulators of these four-Fermi models. This yields a promising alternative to characterize the strongly-coupled fixed points and, moreover, could also explore real-time dynamics and finite-fermion densities.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Contains fulltext : 202254.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCI as a novel approach to estimating osteoarthritis progression. METHODS: Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCI was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error. RESULTS: Between consecutive years, 57-69% of participants had an apparent decrease (change

The basal ganglia (BG) are a group of subcortical nuclei responsible for motor control, motor learning and executive function. Central to BG function are striatal medium spiny neurons (MSNs) expressing D1 and D2 dopamine receptors. D1 and D2 MSNs are typically considered functional antagonists that facilitate voluntary movements and inhibit competing motor patterns, respectively. While their opposite role is well documented for certain sensorimotor loops of the BG-thalamocortical network, it is unclear whether MSNs maintain a uniform functional role across the striatum and which influence they exert on brain areas outside the BG. Here, we addressed these questions by combining optogenetic activation of D1 and D2 MSNs in the mouse ventrolateral caudoputamen (vl CPu) with whole-brain functional MRI (fMRI) recordings. Neuronal excitation of either cell population in the vl CPu evoked distinct activity patterns in key regions of the BG-thalamocortical network including the pallidum, thalamus and motor cortex. Importantly, we report that striatal D1 and D2 MSN stimulation differentially engaged cerebellar and prefrontal regions. We characterised these long-range interactions by computational modelling of effective connectivity and confirmed that changes in D1 / D2 output drive functional relationships between regions within and beyond the BG. These results suggest a more complex functional organization of MSNs across the striatum than previously anticipated and provide evidence for the existence of an interconnected fronto - BG - cerebellar network modulated by striatal D1 and D2 MSNs.Graphical Abstract

Purpose\ud \ud Women’s worry about developing breast cancer may influence their decision to use preventive therapy. However, the direction of this relationship has been questioned. We prospectively investigated the relationship between breast cancer worry and uptake of preventive therapy. The socio-demographic and clinical factors associated with high breast cancer worry were also investigated.\ud \ud \ud \ud Methods\ud \ud Women at increased risk of developing breast cancer were recruited from clinics across England (n = 408). Participants completed a survey on their breast cancer worry, socio-demographic and clinical factors. Uptake of tamoxifen was recorded at 3 months (n = 258 women, 63.2%). Both primary and sensitivity analyses were conducted using different classifications of low, medium and high worry.\ud \ud \ud \ud Results\ud \ud 39.5% of respondents reported medium breast cancer worry at baseline and 21.2% reported high worry. Ethnic minority women were more likely to report high worry than white women (OR = 3.02, 95%CI 1.02, 8.91, p = 0.046). Women educated below degree level were more likely to report high worry than those with higher education (OR = 2.29, 95%CI 1.28, 4.09, p = 0.005). No statistically significant association was observed between worry and uptake. In the primary analysis, fewer respondents with medium worry at baseline initiated tamoxifen (low worry = 15.5%, medium = 13.5%, high = 15.7%). In the sensitivity analysis, participants with medium worry reported the highest uptake of tamoxifen (19.7%).\ud \ud \ud \ud Conclusions\ud \ud No association was observed between worry and uptake, although the relationship was affected by the categorisation of worry. Standardised reporting of the classification of worry is warranted to allow transparent comparisons across cohorts.

The impact of stress on gene expression in different cell types of the brain remains poorly characterized. Three pioneering studies have recently used translating ribosome affinity purification followed by RNA sequencing (TRAP-seq) to assess the response to stress in CA3 pyramidal neurons of the hippocampus. The results suggest that acute stress alters the translation of thousands of genes in CA3 pyramidal neurons, and that this response is strongly modulated by factors such as sex, genotype and a history of early life stress. However, our reanalysis of these datasets leads to different conclusions. We confirm that acute stress induces robust translational changes in a small set of genes. However, we found no evidence that either early life stress or sex have an effect on gene translation induced by acute stress. Our findings highlight the need for additional studies with adequate sample sizes and proper methods of analysis to assess the impact of stress across cell types in the brain.

We show that ultra-cold atoms with synthetic spin-orbit coupling in Raman lattices can be used as versatile quantum simulators to explore the connections between correlated Chern insulators and strongly-coupled four-Fermi field theories related to the Gross-Neveu model in (2+1) dimensions. Exploiting this multidisciplinary perspective, we identify a large-$N$ quantum anomalous Hall (QAH) effect in absence of any external magnetic field, and use it to delimit regions in parameter space where these correlated topological phases appear, the boundaries of which are controlled by strongly-coupled fixed points of the four-Fermi relativistic field theory. We further show how, for strong interactions, the QAH effect gives way to magnetic phases described by a two-dimensional quantum compass model in a transverse field. We present a detailed description of the phase diagram using the large-$N$ effective potential, and variational techniques such as projected entangled pairs.

Objectives: Educational interventions by pharmacists for patients with cancer pain aim to improve pain management, but little is known about the different components of interventions and their effectiveness. Our aim was to assess the benefit of pharmacist delivered educational interventions for patients with cancer pain. A systematic review and meta‐analysis of experimental trials testing pharmacist delivered educational interventions for cancer pain was carried out to identify the components of interventions and effectiveness at improving pain‐related outcomes for patients with cancer. A literature review was conducted in EMBASE, MEDLINE, CINAHL, PsycINFO, ASSIA, Web of Science and CENTRAL from inception until January 2018 searching for educational interventions involving a pharmacist for patients with cancer pain. Four studies were included involving 944 patients. Meta‐analysis was carried out where possible. Key findings: Meta‐analysis of three of the four studies found that mean pain intensity in the intervention group was reduced by 0.76 on a 0–10 scale (95% confidence interval), although only two of the studies used validated measures of pain. Improvements in knowledge, side effects and patient satisfaction were seen although with less reliable measures. Summary: Pharmacist educational interventions for patients with cancer pain have been found to show promise in reducing pain intensity. Studies were few and of varying quality. Further, good quality studies should be carried out in this area and these should be comprehensively reported. Trials measuring patient self‐efficacy and patient satisfaction are needed before the impact of the pharmacist delivered interventions on these outcomes can be established.

Jellyfish populations in the southeastern Atlantic off the coast of Namibia have increased subsequent to the decline of small pelagic fisheries at the end of the 1960s, although the environment there has also become warmer and the waters off Walvis Bay have become richer in zooplankton in recent years. Laboratory experiments were conducted with the scyphozoan jellyfish Chrysaora fulgida to investigate the effects of food density (0, 30, 70, 100 or 150 Artemia nauplii 200 ml–1), feeding frequency (once daily or once every third day) and water temperature (12, 16 or 20 °C) on the asexual reproduction, growth and development of polyps. The results of a generalised linear mixed-effects model reveal that all variables impacted asexual reproduction, with greater polyp production attained at higher food concentrations, increased feeding frequencies and increased temperatures. The most common mode of asexual reproduction was by lateral budding. These laboratory results suggest that polyps of C. fulgida may have proliferated off Namibia in recent times, which would contribute to increased numbers of jellyfish there.Keywords: asexual reproduction, Chrysaora fulgida, environmental change, food availability, metagenesis, northern Benguela Current ecosystem, rising temperatures, Scyphozoa

Background\ud \ud \ud \ud The UK National Health Service is striving to improve access to palliative care for patients with advanced cancer however limited information exists on the level of palliative care support currently provided in the UK. We aimed to establish the duration and intensity of palliative care received by patients with advanced cancer and identify which cancer patients are missing out.\ud \ud Methods\ud \ud \ud \ud Retrospective cancer registry, primary care and secondary care data were obtained and linked for 2474 patients who died of cancer between 2010 and 2012 within a large metropolitan UK city. Associations between the type, duration, and amount of palliative care by demographic characteristics, cancer type, and therapies received were assessed using Chi-squared, Mann-Whitney or Kruskal-Wallis tests. Multinomial multivariate logistic regression was used to assess the odds of receiving community and/or hospital palliative care compared to no palliative care by demographic characteristics, cancer type, and therapies received.\ud \ud Results\ud \ud \ud \ud Overall 64.6% of patients received palliative care. The average palliative care input was two contacts over six weeks. Community palliative care was associated with more palliative care events (p

This dissertation consists of three independent studies in labor economics. The second chapter analyzes the long-run consequences of educational expansion. We show both theoretically and empirically how rising university attendance rates of previous generations can explain increasing earnings inequality. Chapter 3 focuses on the intergenerational effects of social networks. The empirical study examines whether the number and characteristics of friendship connections of parents have an impact on occupational choices and expected earnings of children. Finally, the fourth chapter centers on a large-scale field experiment to test the effectiveness of a novel job matching scheme. This unique set-up allows us to learn about the relevance of search frictions in the labor market as well as long-run effects of taking up temporary work.

Microcrystalline cellulose (MCC) fillers were obtained for hybrid composites with high-density polyethylene and lignin. The fillers were obtained from bleached kraft pulp and cotton fibres. The raw materials were treated by the thermocatalytic destruction method and then ground in a ball mill. Treatment conditions were developed for each raw material. MCC powder samples were obtained, which contained microparticles of different shape and size. Composite samples, which contained polyethylene, 50% of lignin, 20% of MCC and a coupling agent, were produced. It was established that the mechanical properties of composites were improved to a greater extent by the MCC filler obtained from cotton fibres. This can be related to the fact that it contained longer fibre fragments in comparison with wood pulp MCC. The higher degree of crystallinity of cotton cellulose also played a part.

Opioids are important in the management of pain in patients with cancer. Clinicians and patients are sometimes concerned about the effect of opioids on survival, which might decrease opioid prescription, compliance and symptom control. We wanted to determine whether opioid analgesia was associated with shorter survival in adult patients with cancer. We systematically searched for studies that assessed the effect of regular systemic opioid analgesia on survival. We identified 526 unique records, with 20 articles meeting inclusion criteria. Thirteen end-of-life studies, including 11 very low quality retrospective studies, did not find a consistent association between opioid analgesic treatment and survival, this evidence comes from low quality studies, so should be interpreted with caution. Seven longer-term studies, including 3 randomised controlled trials and 2 prospective studies were included. Six of these studies indicated that opioids were likely to be associated with a shorter survival. None of these studies were powered to assess the effect of opioids on survival as a primary endpoint. In view of this, no definitive conclusions can be made as to whether opioids affect survival in cancer patients. These data suggest that while opioid analgesia does not affect survival at the end of life, in the context of longer-term treatment, higher quality studies, with survival as a primary endpoint, are needed to confirm an independent association between opioid analgesia and shorter survival. An important limitation of research in this field is that the relationship between greater analgesic requirements and shorter survival may be mediated by painful progressive cancer.

This paper examines whether children are better off if their parents have stronger social networks. Using data on high-school friendships of parents, we analyze whether the number and characteristics of friends affect the labor-market outcomes of children. While parental friendships formed in high school appear long lasting, we find no significant impact on their children's occupational choices and earnings prospects. These results do not change when we account for network endogeneity, network persistency and network measurement error. Only when children enter the labor market, we find that friends of parents have a marginally significant but small influence on the occupational choice of children.

We report on the mid-infrared nonlinear photothermal spectrum of the neat liquid crystal 4-Octyl-4'-Cyanobiphenyl (8CB) using a tunable Quantum Cascade Laser (QCL). The nonequilibrium steady state characterized by the nonlinear photothermal infrared response undergoes a supercritical pitchfork bifurcation. The bifurcation, observed in heterodyne two-color pump-probe detection, leads to ultrasharp nonlinear infrared spectra similar to those reported in the visible region. A systematic study of the peak splitting as function of absorbed infrared power shows the bifurcation has a critical exponent of 0.5. The surprising observation of an apparently universal critical exponent in a nonequilibrium state is explained using a simple model reminiscent of mean field theory. Apart from the intrinsic interest for nonequilibrium studies, nonlinear photothermal methods lead to a dramatic narrowing of spectral lines, giving rise to a potential new contrast mechanism for the rapidly emerging new field of mid-infrared microspectroscopy using QCLs., Comment: 15 pages, 5 figures, preprint

There is a continuing need to develop new techniques for the rapid and specific identification of bacterial pathogens in human body fluids especially given the increasing prevalence of drug resistant strains. Efforts to develop a surface enhanced Raman spectroscopy (SERS) based approach, which encompasses sample preparation, SERS substrates, portable Raman microscopy instrumentation and novel identification software, are described. The progress made in each of these areas in our laboratory is summarized and illustrated by a spiked infectious sample for urinary tract infection (UTI) diagnostics. SERS bacterial spectra exhibit both enhanced sensitivity and specificity allowing the development of an easy to use, portable, optical platform for pathogen detection and identification. SERS of bacterial cells is shown to offer not only reproducible molecular spectroscopic signatures for analytical applications in clinical diagnostics, but also is a new tool for studying biochemical activity in real time at the outer layers of these organisms.

The native species of amphibians and reptiles of Uruguay were categorized according to the IUCN Red List criteria. Out of 47 amphibian species, seven are listed as Critically Endangered (CR), five as Endangered (EN), one as Vulnerable (VU), three as Near Threatened (NT), and two as Data Deficient (DD); the remaining species are considered to be Least Concern (LC). Among the 64 species of reptiles evaluated, one is listed as Critically Endangered (CR), seven as Endangered (EN), two as Vulnerable (VU), one as Near Threatened (NT) and seven as Data Deficient (DD); the rest are considered to be Least Concern (LC). The use of these results as an additional criterion in the definition of protected areas in Uruguay will contribute towards the conservation of the aforementioned threatened species and their associated ecosystems. Las especies nativas de anfibios y reptiles de Uruguay fueron categorizadas de acuerdo a los criterios de la Lista Roja de UICN. De las 47 especies de anfibios, siete se encuentran En Peligro Crítico (CR), cinco En Peligro (EN), una Vulnerable (VU), tres Casi Amenazadas (NT), y dos con Datos Deficientes (DD); las especies restantes son consideradas como Preocupación Menor (LC). Entre las 64 especies de reptiles evaluados, una se encuentra en Peligro Crítico (CR), siete En Peligro (EN), dos como Vulnerables (VU), una Casi Amenazadas (NT) y siete con Datos Deficientes (DD); las especies restantes son consideradas como Preocupación Menor (LC). El uso de estos resultados como un criterio adicional en la definición de áreas protegidas en Uruguay contribuirá hacia la conservación de dichas especies amenazadas y sus ecosistemas asociados.

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Objective. To evaluate the efficacy and safety of three dosing and repeat treatment regimens of rituximab (RTX) plus MTX in patients with active RA. Methods. Patients with active RA despite stable MTX (10–25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 × 500 and 2 × 500 mg; 2 × 500 and 2 × 1000 mg (dose escalation); and 2 × 1000 and 2 × 1000 mg. The primary endpoint was proportion of patients achieving ACR20 at Week 48. Results. At Week 48, ACR20 responses were not statistically significantly different between the dose regimens. Compared with RTX 2 × 500 mg (n = 134) or dose escalation (n = 119), ACR and European League Against Rheumatism (EULAR) outcomes in the RTX 2 × 1000 mg group (n = 93) were consistently higher, with significantly more patients achieving EULAR responses (P = 0.0495). At Week 48, rituximab 2 × 1000 mg was associated with a higher proportion of patients who, following retreatment, maintained or improved their Week 24 responses. Dose escalation from 2 × 500 to 2 × 1000 mg did not appear to be associated with improved outcomes compared with continual 2 × 500 mg. All RTX regimens demonstrated comparable safety. Conclusions. RTX 2 × 500 and 2 × 1000 mg could not be clearly differentiated, although some efficacy outcomes suggest improved outcomes in the rituximab 2 × 1000 mg group. Retreatment from Week 24 resulted in a sustained suppression of disease activity through to Week 48. Trial registration. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00422383.

Objective: To study the feasibility and validity of a two-step telephone screening procedure for symptomatic knee and hip osteoarthritis (OA) in the general population. Method: The screening questionnaire was based on signs and symptoms, previous diagnosis of OA, and validated OA criteria. A random sample of telephone numbers was obtained and, at each number, one individual aged 40 to 75 years was included. A physical examination and knee or hip radiographs were offered when the screen was positive. A sample of individuals with negative screens was also examined. The diagnosis of hip/knee OA was based on the American College of Rheumatology criteria for signs and symptoms and Kellgren-Lawrence radiographic stage 2 or greater. Prevalence rates were estimated with correction for the performance of the screening procedure. Results: Of 1380 individuals, 479 had positive screens, among whom 109 were evaluated; Symptomatic radiographic OA was found in 50 individuals, at the knee (n=35) or hip (n=20). Corrected prevalence estimates of symptomatic OA were 7.6% [6.4-8.8] for the knee and 5% (3.9-6.1) for the hip. The screening procedure had 87% [95% confidence interval [95%CI], 79-95%] sensitivity, and 92% [95% CI: 91-93] specificity for detecting knee OA and respectively 93% [95% CI: 86-100] and 93% [95% CI: 92-94] for hip OA. Conclusion: This study establishes the feasibility of a telephone screening for symptomatic knee/hip OA, which could be used for a nationwide prevalence study. Pain and previous OA diagnosis were the best items for detecting symptomatic OA.

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The expectations of patients with osteoarthritis are essential for health care provision and may be used to improve the patient-doctor relationship. Methods: A total of 96 osteoarthritis patients aged 42-89 years (mean = 65; 81% female) were recruited among customers of 10 pharmacies in 10 towns in 10 regions (selected at random from the 22 French regions). Ten focus groups were organized looking at three categories of expectation: 1) Information about and understanding of osteoarthritis; its impact on lifestyle, and its treatment, consequences, and outlook; 2) Communication skills, attitudes of practitioners and communication between health professionals; 3) Support available from doctors, family circle and society. Results: The patient-practitioner relationship begins with a dialogue. Participants suggested that its quality can be improved by: Developing greater trust: patients expect communication skills and expressions of sympathy that practitioners seem ill-prepared to provide. Strengthening involvement: general practitioners in particular should act as mediators and facilitators to improve recognition and understanding of osteoarthritis by employers and public decision-makers. Conclusions: The present study enabled patients to express their expectations. Meeting those expectations could markedly improve the therapeutic process, but the question arises of whether practitioners are ready to agree that there is a need to reconsider and modify the care they provide for their patients.

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