bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytogenetic effects among workers exposed to formaldehyde. The possible role of some polymorphisms
Authors: Ghelli F , Bellisario V , Buglisi M , Cocchi E , Bono R , Santovito A
Published: October 2020

Background

Formaldehyde (FA) is a human carcinogen. It is commonly used in diluted form as formalin. The purpose of this work was to evaluate the frequencies of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as a consequence of the exposure to FA in a hospital setting, taking into account the role of some polymorphisms in developing genotoxic damage.

Methods

CAs and SCEs assays were performed on peripheral blood lymphocytes of 57 pathologists enrolled in Turin hospitals (Italy) and 48 unexposed enrolled as controls. All subjects were genotyped for CYP1A1 exon 7 (A>G), CYP1A1*2A (T>C), CYP2C19*2 (G>A), GSTT1 (Positive/Null), GSTM1 (Positive/null), GSTP1 (A>G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPD (A751C), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα -308 (G>A), IL10 -1082 (G>A), IL10 -819 (C>T) and IL6 -174 (G>C) gene polymorphisms. Due to the little number of recessive homozygotes, we compared the dominant genotype with the combined group of heterozygotes and recessive homozygotes.

Results

Among pathologists, the mean value of personal air-FA was 64.2 µg/m3, mean significantly higher (p = 0.000) than controls (19.1 µg/m3). Similarly, pathologists showed significantly higher values of SCEs (p = 0.009) and CAs (p = 0.000) with respect to controls. In the same group, CYP2C19*2 (p = 0.011), XRCC1 (G399A) (p = 0.007), and IL10 (-1082) (p = 0.042) gene polymorphisms influenced the CAS levels, as well as those of CYP1A1 exon 7 (p = 0.010), XPD A751C (p = 0.002), XPC C499T (p = 0.040), and IL10 (-819) (p = 0.005) the levels of SCEs. In control group, CAs resulted significantly lower in CYP1A1 exon 7 dominant homozygotes (p = 0.001).

Conclusions

Our study confirms the role of FA as an inductor of genotoxicity, even when, daily, workers are exposed to low FA levels. Some genetic polymorphisms seem to have an influence in modulating the effect of FA exposure, highlighting, in occupational health studies, the role of the individual susceptibility.

Key messages

FA exposure is confirmed to be a genotoxicity inductor even at low concentrations. Some genetic polymorphisms seem to have a role in the modulation of FA exposure-related damage.
Stress levels among workers: an observational study
Authors: Testa T , Comba M , Nicolini D , Rinaldi C , Opizzi A , Concina D , Panella M
Published: October 2020

Introduction

While some stress is a common part of everyday work for most people, higher or prolonged levels of stress might be harmful. Work-related stress is becoming a study subject because of its important implications: it is related to coronary heart disease and health in general and it also influences employee satisfaction and productivity. Because of this, workers should be aware of their stress levels in order to prevent disease and increase performance levels. Therefore, the aim of our study was to evaluate stress levels among employees.

Methods

We conducted an observational study in collaboration with Anteo, an onlus society based in Biella which employs more than 1000 workers. The first step of our study ran from December 2019 to February 2020, and included 300 workers. Informed consent was gathered trough structure chiefs prior to the intervention. We administered an online questionnaire based on the Kessler Psychological Distress Scale (K10) for screening than, subjects with a high perceived stress level were invited for a personal interview with our medical and psychological staff.

Results

The response rate was 31% with 94 questionnaires completed by the end of February 2020. 80% of respondents were women (75 out of 94). 17% of the employees presented a moderate to high level of stress (16 total, 72% women). Only 5% of workers presented a high level of stress (4 total, 50% women). All Patients presenting a high level of perceived stress went through medical and psychological evaluation, which confirmed the results in 88% cases (14 out of 16).

Conclusions

Our study evidenced that workers are often exposed to high levels of stress, which can influence health, everyday life as well as productivity. The introduction of stress management programs in companies could improve workers health and productivity having a positive impact on one's health, company productivity and society in general.

Key messages

The introduction of stress management programs might improve workers health and productivity. The introduction of stress management programs might have a positive impact on one’s health, company productivity and society in general.
What weights on the user experience of hospital inpatient episodes? A Portuguese national study
Authors: Galhano Lopes D , Nicola P , Esteves H
Published: October 2020

Background

Information about the users' experience is an essential element in patient-centered healthcare. We determined the score of the different elements of inpatient experiences of admission episodes in hospitals of the Portuguese health system and examined their contribution to the overall experience score.

Methods

A national cross-sectional study using randomized telephone interviews was conducted in the general population for the last episode of individuals who had an episode of hospitalization care between November 2016 and October 2017. Descriptive analysis of sociodemographic characteristics, care episode, hospital, elements of experience (16 dimensions), and global opinion was performed. The elements of experience were compared with the global experience through Spearman's correlation, with the contribution of each element to the global opinion calculated through weighted least squares regression.

Results

We obtained a total of 308 responses, 60.7% were female and the average age was 53.1 years, the average length of stay was 8.06 days; 35.1% were in medical departments; 56.5% were elective; 43.8% hospitals were in the Lisbon Metropolitan Area and 88.3% were from the public health service. All elements of experience and the overall opinion presented median values between 3 and (the maximum) 4. The correlation of each element with the global opinion is positive and statistically significant, having a contribution to the global opinion which varies between 11.5% and 51.6%, independently of demographic, episode of care or hospital characteristics. The domains of emotional support, empathy and respect; and communication, information and personal interaction make the greatest contribution to global opinion.

Conclusions

Elements of experience do not have the same weight on the global evaluation of inpatient individuals, which seem to privilege relational and interpersonal aspects of care. These findings have implications for patient-centered healthcare.

Key messages

Most users are satisfied with their hospitalization episodes of the Portuguese health system. The elements that contribute the most to the experience have to do with the healthcare workforce and their interaction with the users.
Barriers to reproductive health services utilization among adolescents
Authors: Hayrumyan V , Grigoryan Z , Sargsyan Z , Harutyunyan A , Petrosyan V
Published: October 2020

Background

Adolescents' access to quality reproductive health services is crucial for their psychosocial and physical wellbeing. Yet, adolescents encounter various barriers while utilizing reproductive health services, globally. Adolescent-friendly health services (AFHS) is an evidence-based intervention to meet the reproductive health needs inclusively of all adolescents. The study aimed to explore adolescents' experiences while seeking reproductive health services in primary healthcare facilities (PHCF) in Armenia.

Methods

We conducted a qualitative cross-sectional study using in-depth interviews, focus group discussions and observations of PHCFs. The study participants included adolescents (aged 18-19 years) (n = 17), PHC providers (PHP) (n = 29), managers of PHCFs (n = 7) and experts in the field of adolescent health (n = 5) from the two largest cities in Armenia. The Global standards for quality healthcare services for adolescents guided the instrument development process and deductive content analysis.

Results

Barriers to the utilization of reproductive health services by adolescents at PHCFs were related to various personal, cultural, and social factors. PHPs and experts blamed adolescents' insufficient knowledge of reproductive health and related services for being a major barrier. However, adolescents' reported a different set of important barriers to reproductive health services: PHPs' judgmental attitude, lack of efforts to protect privacy and confidentiality (due to lack of PHP competencies to provide AFHS and inadequate PHCF infrastructure), negative public opinion and lack of community support.

Conclusions

The study findings shed light on different perspectives related to various challenges adolescents come across in PHCFs. Addressing identified barriers have the potential of positively influencing adolescents' experiences while utilizing reproductive health services in PHCFs.

Key messages

Adolescents’ insufficient knowledge, PHPs’ judgmental attitude, lack of privacy and confidentiality, and negative public opinion are among the main barriers to the reproductive health services. Further enforcement of adolescent-friendly health services in primary healthcare facilities is needed to ensure accessibility of quality reproductive health services for all adolescents.
Strategies for improving primary care for adolescents and young adults transitioning from pediatric services: perspectives of Canadian primary health care professionals
Authors: Schraeder Kyleigh , Dimitropoulos Gina , Allemang Brooke , McBrien Kerry , Samuel Susan
Published: October 2020

Background

Family physicians and other members of the primary health care (PHC) team may be ideally positioned to provide transition care to adolescents and young adults (AYAs; aged 12–25 years) exiting pediatric specialty services. Potential solutions to well-known challenges associated with integrating PHC and specialty care need to be explored.

Objective

To identify strategies to transition care by PHC professionals for AYAs with chronic conditions transitioning from pediatric to adult-oriented care.

Methods

Participants were recruited from six Primary Care Networks in Calgary, Alberta. A total of 18 semi-structured individual interviews were completed, and transcribed verbatim. Data were analyzed using a qualitative description approach, involving thematic analysis.

Results

Participants offered a range of strategies for supporting AYAs with chronic conditions. Our analysis resulted in three overarching themes: (i) educating AYAs, families, and providers about the critical role of primary care; (ii) adapting existing primary care supports for AYAs and (iii) designing new tools or primary care practices for transition care.

Conclusions

Ongoing and continuous primary care is important for AYAs involved with specialty pediatric services. Participants highlighted a need to educate AYAs, families and providers about the critical role of PHC. Solutions to improve collaboration between PHC and pediatric specialist providers would benefit from additional perspectives from providers, AYAs and families. These findings will inform the development of a primary care-based intervention to improve transitional care.
Who is entitled to feel in the age of populism? Women's resistance to migrant detention in Britain
Authors: Bilgic Ali , Gkouti Athina
Published: October 2020

European states have adopted strict migration policies, such as unlimited detention in Britain, to address increasing anti-immigrant emotions in the context of rising anti-immigrant populism. These state practices prioritize the feelings of insecurity of some population groups towards immigrants whose emotions and insecurities are politically marginalized. Consequently, whose emotions matter in politics intertwines with whose security matters. This article articulates emotions in politics of security as an entitlement, which feed into the question of who ‘merits’ security politically. By focusing on individuals to whom such entitlement is denied in the context of anti-immigrant populism, it investigates how immigrant women ‘feel’ detention and enact their emotions in their own everyday ‘felt’ security. The research is conducted through in-depth interviews with women who experienced detention in Britain. Through the method of ‘listening guide’ adapted from psychology, the research studies their narratives about their emotions before, during and after detention. By bringing together the feminist research on emotions and ‘everyday security’ approaches in International Relations, this analysis contributes to feminist IR and security studies on women's agency in the politics of security, by revealing the importance of emotional dynamics in their everyday ‘felt’ security practices. Therefore, it offers a path for feminist IR and security studies to prioritize those whom anti-immigrant populism aims to silence in the age of populism.
Female peacekeepers’ added burden
Authors: Wilén Nina
Published: October 2020

Twenty years since the adoption of UN Security Council Resolution 1325 there is an almost unanimous call for an increased number of uniformed women in peace operations from policy-makers and multilateral organizations. This continuous push for the inclusion of more women is often justified by arguments about an increased operational effectiveness related to women's ‘added value’: both implicitly and explicitly advocating for greater gender equality. Yet, in this article, I contend that using instrumentalist arguments to increase the number of female peacekeepers may on the contrary undermine gender equality. This is related to the risk of producing self-fulfilling prophecies whereby female peacekeepers try to live up to the high expectations by fitting into gender-stereotypes and/or by working harder than their male colleagues. Rather than increase gender equality, such efforts risk transforming the female ‘added value’ to an ‘added burden’ which male peacekeepers do not have to carry. Anchoring the study in feminist theory with the aim to understand gendered relations of power, to illustrate my argument I draw on extensive interview material from military staff and peacekeepers in South Africa, Burundi, Belgium and Niger; interviews and informal discussions with female and male peacekeepers; and participation in several policy and research workshops on female participation in peacekeeping.
The dynamics of prototypical police forces: lessons from two Somali cities
Authors: Hills Alice
Published: October 2020

Sooner or later, donor-led discussions of state- and institution-building in conflict-affected societies with low literacy rates address the role of police forces, which are to be developed in the light of community-oriented policing. However, the implementation of a basic policing programme in the Somali cities of Kismayo and Baidoa in 2014 raises important questions about the applicability of this approach. It suggests that, rather than police in the western sense of the word, Somali forces are part of an endemic power structure that accommodates and normalizes instability. Focusing on what police officers actually do and on what local residents expect from them, this article uses three practical indicators to explore the factors at work: recruitment, reward (i.e. stipends) and, importantly, retention. This pragmatic approach allows an analytical and empirical exploration of a prototypical form of police and policing in a society lacking meaningful state-based institutions and processes. Specifically, Kismayo's and Baidoa's experience helps to identify the minimal requirements needed for formal policing in unstable societies. It suggests that militia-style policing is residual, rather than novel, and its dynamics are best understood as reflecting a series of social and political influences within unequal fields of power, with the emphasis on exploitation and survival.
The unintended impact of the European discard ban
Authors: Borges Lisa
Published: October 2020

The European Union (EU) discard ban, called the landing obligation (LO), was initiated in 2015 to reduce unwanted catches by EU fisheries. To ease the transition to a system where total allowable catches (TACs) refer to catches rather than landings only, the majority of EU TACs was increased to account for the part of the catch that was previously discarded and would now be landed. The analysis shows an average annual upward adjustment of 36% in TACs since 2015, but these percentages were considerably higher in 2019 and 2020 (reaching 43 and 50%, respectively), when the LO was fully applicable to all fisheries, and particularly for TACs of demersal species (reaching 51 and 60%). These results demonstrate the significant impact that the discard ban has had on the quantities of EU fishing opportunities. Since discarding has not declined in EU fisheries at any significant level, the magnitude of these increases may likely have resulted in a substantial widespread increase in fishing mortality being exerted on European stocks, and thus likely lead to an implosion of the EU TAC system, the Common Fisheries Policy central instrument to manage fisheries in the EU.
A strong order 3/4 method for SDEs with discontinuous drift coefficient
Authors: Müller-Gronbach Thomas , Yaroslavtseva Larisa
Published: October 2020

In this paper we study strong approximation of the solution of a scalar stochastic differential equation (SDE) at the final time in the case when the drift coefficient may have discontinuities in space. Recently, it has been shown in Müller-Gronbach & Yaroslavtseva (2020, On the performance of the Euler–Maruyama scheme for SDEs with discontinuous drift coefficient. Ann. Inst. Henri Poincaré Probab. Stat., 56, 1162–1178) that for scalar SDEs with a piecewise Lipschitz drift coefficient, and a Lipschitz diffusion coefficient that is nonzero at the discontinuity points of the drift coefficient the classical Euler–Maruyama scheme achieves an $L_p$-error rate of at least $1/2$ for all $p\in [1,\infty )$. Up to now this was the best $L_p$-error rate available in the literature for equations of that type. In the present paper we construct a method based on finitely many evaluations of the driving Brownian motion that even achieves an $L_p$-error rate of at least $3/4$ for all $p\in [1,\infty )$ under additional piecewise smoothness assumptions on the coefficients. This is the first higher order method known in the literature for SDEs of that type. We add that the $L_p$-error rate $3/4$ cannot be improved in general. To obtain the upper error bound for our new method, we prove in particular that a quasi-Milstein scheme achieves an $L_p$-error rate of at least $3/4$ in the case of coefficients that are both Lipschitz continuous and piecewise differentiable with Lipschitz continuous derivatives, which is of interest in itself. The latter error rates are obtained via a detailed analysis of the average size of increments of the time-continuous quasi-Milstein scheme over time intervals in which the scheme crosses a point of nondifferentiability of the coefficients.
Special Programme for Research and Training in Tropical Diseases-coordinated Multicountry Study to Determine the Burden and Causes of Residual Malaria Across Different Regions
Authors: Fouque Florence , Knox Tessa
Published: October 2020

The burden and causes of residual malaria were investigated between 2015 and 2019 through 5 research projects coordinated by the Special Program for Research and Training in Tropical Diseases (TDR), cosponsored by the United Nations Development Programme, UNICEF, the World Bank, the World Health Organization (WHO) and the WHO Global Malaria Programme. The 5 projects included 10 countries in 4 WHO regions: Africa, the Americas, South-East Asia, and the Western Pacific. The countries represented a range of malaria endemicities, from low to high levels of transmission. The main findings of the projects indicate that overall the core malaria vector control tools (long-lasting insecticidal nets [LLIN] and indoor residual spraying) were not deployed in the optimal way and/or not efficient in many settings of the supported projects. Furthermore, vector biting behavior and human activity–associated factors strongly contributed to malaria persistence. Changes in vector species composition and abundance, with an increase in outdoor biting, were also reported. Some of these factors may be an adaptation of the vectors to the deployment of the tools and/or can be linked to other sectors, such as agricultural practices, environmental changes, social factors, and water management. Human behaviors and sleeping habits that included activities and sleeping outside villages in unprotected dwellings were another part of the problem. The evidence collated demonstrates the need for new approaches, such as the multisectoral one and new vector control tools, all adapted to the local contexts and integrated into current malaria programs.
‘Chinese’ hegemony from a Korean shi perspective: aretocracy in the early modern East Asia
Authors: Choi Inho
Published: October 2020

The study of pre-modern Chinese hegemony is crucial for both theorizing hegemony and envisioning a new global order. I argue the pre-modern Chinese hegemony was a reciprocal rule of virtue, or aretocracy, driven by the transnational sociocultural elites shi. In contrast to the prevailing models of Chinese hegemony, the Early Modern East Asia was not dominated by the unilateral normative influence of the Chinese state. The Chinese and non-Chinese shi as non-statist sociocultural elites co-produced, through their shared civilizational heritage, a hegemonic order in which they had to show excellence in civil virtues to wield legitimate authority. In particular, the Ming and Chosŏn shi developed a tradition of envoy poetry exchanges as a medium for co-constructing Chinese hegemony as aretocracy. The remarkable role of excellent ethos for world order making in Early Modern East Asia compels us to re-imagine how we conduct our global governance.
Fluoroquinolone resistance in Achromobacter spp.: substitutions in QRDRs of GyrA, GyrB, ParC and ParE and implication of the RND efflux system AxyEF-OprN
Authors: Magallon Arnaud , Roussel Mathilde , Neuwirth Catherine , Tetu Jennifer , Cheiakh Anne-Charlotte , Boulet Baptiste , Varin Véronique , Urbain Victor , Bador Julien , Amoureux Lucie
Published: October 2020

Background

Achromobacter are emerging pathogens in cystic fibrosis patients. Mechanisms of resistance to fluoroquinolones are unknown in clinical isolates. Among non-fermenting Gram-negative bacilli, fluoroquinolone resistance is mostly due to amino acid substitutions in localized regions of the targets (GyrA, GyrB, ParC and ParE) named QRDRs, but also to efflux.

Objectives

To explore quinolone resistance mechanisms in Achromobacter.

Methods

The putative QRDRs of GyrA, GyrB, ParC and ParE were sequenced in 62 clinical isolates, and in vitro one-step mutants obtained after exposure to fluoroquinolones. An in vitro mutant and its parental isolate were investigated by RNASeq and WGS. RT–qPCR and gene inactivation were used to explore the role of efflux systems overexpression.

Results

We detected seven substitutions in QRDRs (Q83L/S84P/D87N/D87G for GyrA, Q480P for GyrB, T395A/K525Q for ParE), all in nine of the 27 clinical isolates with ciprofloxacin MIC ≥16 mg/L, whereas none among the in vitro mutants. The RND efflux system AxyEF-OprN was overproduced (about 150-fold) in the in vitro mutant NCF-39-Bl6 versus its parental strain NCF-39 (ciprofloxacin MICs 64 and 1.5 mg/L, respectively). A substitution in AxyT (putative regulator of AxyEF-OprN) was detected in NCF-39-Bl6. Ciprofloxacin MIC in NCF-39-Bl6 dropped from 64 to 1.5 mg/L following gene inactivation of either axyT or axyF. Substitutions in AxyT associated with overexpression of AxyEF-OprN were also detected in seven clinical strains with ciprofloxacin MIC ≥16 mg/L.

Conclusions

Target alteration is not the primary mechanism involved in fluoroquinolone resistance in Achromobacter. The role of AxyEF-OprN overproduction was demonstrated in one in vitro mutant.
Conscientious Objection in Health Care: Pinning down the Reasonability View
Authors: McConnell Doug
Published: October 2020

Robert Card’s “Reasonability View” is a significant contribution to the debate over the place of conscientious objection in health care. In his view, conscientious objections can only be accommodated if the grounds for the objection meet a reasonability standard. I identify inconsistencies in Card’s description of the reasonability standard and argue that each version he specifies is unsatisfactory. The criteria for reasonability that Card sets out most frequently have no clear underpinning principle and are too permissive of immoral objections. Card has also claimed that petitioners must justify their positions with Rawlsian public reason. I argue that, although the resulting reasonability standard is principled, it is overly restrictive. I also show that a reasonability standard built on Rawls’ more lenient conception of reasonableness would be overly permissive of objections at odds with professional healthcare standards. Finally, I argue for my favored solution, which bases the reasonability standard on minimal professional standards.
A life course approach for understanding later life sustainability
Authors: Dodds Richard , Syddall Holly , Sayer Avan Aihie
Published: October 2020

This chapter describes a life course approach for understanding later life sustainability, focusing on grip strength as a marker of physical sustainability, and explaining how a life course approach recognizes that muscle strength in later life reflects not only rate of loss in later life, but also the peak attained earlier in life. We present evidence that risk factors operating throughout the life course have an impact on physical sustainability in later life with particular consideration of the effects of body size, socioeconomic position, long-term conditions, physical activity, diet, and smoking. We have shown that low birth weight is associated with weaker grip strength across the life course and that there is considerable evidence for developmental influences on ageing skeletal muscle. Finally, a life course approach suggests opportunities for early intervention to promote later life physical sustainability; but optimal strategies and timings for intervention are yet to be identified.
Integration of vaccination of older adults in a life course programme
Authors: Michel Jean-Pierre , Ecarnot Fiona
Published: October 2020

Vaccines represent the medical intervention that has yielded the greatest benefit on human health and longevity. Focusing on life course immunization means adopting a temporal and societal perspective towards the health of individuals and cohorts. Increasing numbers of epidemiological examples from influenza, pertussis, and pneumococcal vaccines, but also CMV, diphtheria, pertussis, and varicella vaccines provided (or administered) at a young age testify to the importance of community protection against preventable infectious diseases and chronic diseases at the level of the oldest adults, who exhibit immunosenescent defects. In parallel, the current low vaccine coverage rate among healthcare workers disadvantages their older patients, as well as themselves and their relatives. Thus, a vaccination programme focusing only on old adults will be less effective than a global life course immunization program fully integrated into a comprehensive lifecourse ‘healthy ageing’ program.
Why, when, and where do older people die?
Authors: Prsic Elizabeth H. , Spear Rebecca A. , Teno Joan M.
Published: October 2020

The demographics of death among older persons have changed markedly over the past century. Individuals are living longer, but gains in life expectancy differ significantly between low-, middle-, and high-income countries. While individuals would previously succumb to infectious disease after a brief illness, older persons often suffer long periods of morbidity at the end of life in the setting of chronic, non-communicable diseases. With increased care needs at the end of life, older persons are more likely to die in an institutional setting, despite preferences for death at home. While site of death has been proposed as a quality metric, it captures only one aspect of the trajectory of end-of-life care. This chapter explores various aspects of death among older persons, and places the subject in a larger geographic, medical, and socioeconomic context.
Evolution and cancer
Authors: Donnem Tom , Micklem Kingsley , Pezzella Francesco
Published: October 2020

Evolution is the process by which living organisms change through time, and natural selection is the process which leads some organisms to thrive and others to die out. Evolutionary medicine tries to explain why traits leading to susceptibility to disease get maintained or even positively selected. Cancer, being a genetic disease, can be analysed as an example of evolution by natural selection. The observation that humans in developed societies have much higher rates of cancer can be analysed and explained by an evolutionary approach. At a cellular level, tumours are made up by a population of cells continuously growing and mutating while interacting with the microenvironment of the body. Thus, the mechanism of changes in individual tumours is the process of natural selection. Evolutionary biology is now increasingly used to better understand tumour growth and therefore to improve treatments.
Cancer-associated stroma
Authors: Mesker Wilma , Tollenaar Rob
Published: October 2020

Tumorigenesis is a dynamic process. Research on cancer development and metastases focuses on the tumour ‘host’ interface, and in particular on the role of the stromal tissue. For a few decades now, it has been well established that the tumour-associated stroma affects cancer growth and progression. Fibroblasts of the stroma orchestrate the recruitment of immune cells to promote cancer growth. Moreover, the tumour stroma of each tumour is different in terms of quantity and of cellular composition. The tumour stroma has gained interest in the clinic with regard to patient prognosis and its potential to influence therapy response. Where cancer drug development traditionally focused on targeting the tumour cells, emphasis has now shifted towards the tumour microenvironment for the development of novel therapeutics.
Rheumatoid arthritis—diagnosis
Authors: Aletaha Daniel , Radner Helga
Published: October 2020

Rheumatoid arthritis (RA) is among the most disabling form of chronic inflammatory joint disease. Not all forms of arthritis develop into RA; on the contrary, it may be very challenging to differentiate RA from cases of arthritis that are self-limiting or caused by another disease. Evaluation of early arthritis includes some basic steps, such as excluding trauma, crystal, or infectious-related disease, as well as considering additional features that may guide towards a specific diagnosis. If no specific diagnosis can then be made, the presentation can be labelled as undifferentiated arthritis. Typical differential diagnoses of RA include viral polyarthritis, seronegative spondylarthropathies, polymyalgia rheumatic, and other systemic rheumatic diseases. In 2010, new classification criteria were published that led to a change in the approach to RA. Compared to the previous criteria, the American College of Rheumatology (ACR) 1987 criteria, a scoring system was devised, appreciating the type and number of affected joints (up to 5 points), as well as serology (up to 3 points), elevated acute-phase reactants (1 point), and a symptom persistence of 6 weeks or longer (1 point). If 6 or more points are reached, then classifiable RA is present. Importantly, classification status, which is used for study purposes, is not always identical to the diagnostic status, which often leads to clinical treatment.
Systemic lupus erythematosus—management
Authors: Dey Ida Dzifa , Isenberg David
Published: October 2020

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with varied presentation and a disease course characterized by remission and flares. Over the last 50 years the prognosis of SLE has improved considerably. The introductions of corticosteroids and later of cytotoxic drugs, dialysis, and renal transplantation were the major contributors to this improvement. Nevertheless, the treatment and general management of lupus continues to present a challenge. While lupus may, for some patients, represent a relatively mild set of problems, many others require large doses of immunosuppressive drugs, which carry long-term concerns about side effects. New immunotherapeutic drugs, with actions more closely targeted to the immune cells and molecules involved in the pathogenesis of SLE, are being introduced and the future looks promising. The role of early atherosclerosis and cardiovascular disease as a cause of death in patients with SLE is increasingly recognized and will present further challenges in the future.
Juvenile-onset systemic lupus erythematosus
Authors: Oni Louise , Beresford Michael W.
Published: October 2020

Paediatric or juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune condition, differing from the adult form in terms of severity, organ manifestations, and a less striking female predominance. The diagnosis relies on the adult-derived American College of Rheumatology SLE classification criteria. Genetic, autoantibody, and host immune responses, characteristic of this disease, result in a clinically heterogeneous phenotype. A proportion of paediatric SLE patients will have evidence of a genetic deficiency known to be associated with SLE, such as C1q deficiency, and screening for these is required. A challenging diagnosis to make in the younger age group, the management of JSLE compared to adult-onset SLE requires special consideration towards the significant long-term consequences of the disease and treatment toxicity, combined with an onset during a fundamental time with regards to growth and development. A comprehensive, multidisciplinary team approach to the management of JSLE is essential. With a more severe phenotype and limited comorbidities, patients with JSLE represent an invaluable opportunity for investigating the pathogenesis. To date, clinical trials informing interventions in JSLE are very limited and treatment choices rely on the outcome of adult trials. Patient and family involvement in research to improve outcomes and understanding is essential. New treatments, including biological therapies, are becoming available for clinical use and new treatment combinations have been used to induce and maintain clinical remission.
Overlap/undifferentiated syndromes
Authors: Herrick Ariane , Hughes Michael
Published: October 2020

Undifferentiated connective tissue disease (UCTD) and overlap syndromes both form part of the broad spectrum of connective tissue disease. They are difficult to define, as the boundaries between them and specific diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and myositis are often not clear-cut. This chapter gives a broad overview of diagnosis, clinical features, outcomes, and management. Patients with UCTD have clinical and/or serological features of connective tissue disease but do not fulfil the criteria for any one defined disease. Raynaud’s phenomenon and puffy fingers are often the presenting features but there are many possible others, including arthralgia, sicca symptoms, and breathlessness due to pulmonary fibrosis, usually in the context of a positive anti-nuclear antibody (ANA). A proportion of patients evolve into a defined connective tissue disease: in those who do, this is generally within 5 years of onset. Treatment is dependent upon the clinical features: for example vasodilators for Raynaud’s phenomenon, or hydroxychloroquine for arthralgia/arthritis. Patients with overlap syndromes have features of more than one defined connective tissue disease. Overlap syndromes are therefore highly heterogeneous as many combinations of clinical and serological features can occur. Mixed connective tissue disease (MCTD) is the overlap syndrome that has been most described and includes overlapping features of SLE, SSc, and myositis in patients who are anti-U1 ribonucleoprotein (RNP) antibody positive. Treatment is of the specific clinical manifestations. Patients with overlap syndromes should be kept under regular review to allow early identification of internal organ involvement.
Paget’s disease of bone
Authors: Ralston Stuart H.
Published: October 2020

Paget’s disease of bone (PDB) affects up to 1% of people of European origin aged 55 years and above. It is characterized by focal increases in disorganized bone remodelling which disrupt normal bone architecture, causing the affected bones to enlarge and become weakened. This can lead to various complications including pain, deformity, fracture, nerve compression syndromes, and osteoarthritis. Genetic factors play a key role in the pathogenesis of PDB. This is mediated by a combination of rare genetic variants which cause familial forms of the disease and common variants which have additive effects on disease susceptibility. Suggested environmental factors for PDB include viral infections, calcium and vitamin D deficiency, and excessive mechanical loading of affected bones. The diagnosis can be made by the characteristic changes seen on radiographs, but isotope bone scans are a more sensitive method of defining disease extent. Serum total alkaline phosphatase levels are usually raised in patients with metabolically active disease and are often used as a measure of disease activity. Bisphosphonates are the treatment of choice for PDB; they reduce the elevations in bone turnover that are characteristic of the disease and are an effective treatment for bone pain. Among the bisphosphonates, zoledronic acid is most likely to give a favourable pain response. Bisphosphonate treatment should not be given with the primary aim of normalizing elevated biochemical markers of bone turnover since there is no evidence that this is beneficial. Although potent bisphosphonates can normalize elevated bone turnover in many patients with PDB, it unclear as yet whether this prevents complications of the disease.
Neutrophilic dermatoses
Authors: Moinzadeh Pia , Krieg Thomas
Published: October 2020

Neutrophilic dermatoses (ND) comprise a heterogeneous group of non-infectious skin diseases characterized by a diffuse epidermal and/or dermal infiltrate consisting of polymorphonuclear neutrophilic inflammatory cells throughout the different skin layers. Depending on the localization of this infiltrate, patients may present with a variety of skin lesions such as pustules/vesiculopustules (epidermal infiltrate), plaques or papules (dermal infiltration), nodules or ulcerations (deep dermal/subcutaneous infiltrate) and also with possible systemic symptoms, such as leucocytosis, arthralgias, myalgia, and malaise. Based on the clinical picture of cutaneous lesions and further systemic symptoms the patients can be subdivided into different entities. These include Sweet’s syndrome (SS), pyoderma gangrenosum (PG), rheumatoid neutrophilic dermatitis, bowel-associated dermatosis-arthritis syndrome, subcorneal pustular dermatosis (Sneddon Wilkinson), acute generalized exanthematous pustulosis (AGEP), acrodermatitis continua of Hallopeau (ACH), palmoplantare pustuloses (PPP), pustular bacterid (PB), neutrophilic eccrine hidradenitis, and Behçet’s disease. The pathogenesis is still not fully elucidated but it has been hypothesized that it is associated with immunological dysfunctions, with abnormal cytokine signalling, causing an uncontrolled recruitment of neutrophilic cells. ND can be triggered by underlying systemic inflammatory diseases, malignancies, haematological disorders and/or medication use. Diagnostic procedures include detailed physical examination, laboratory tests, and histopathological assessments. The therapeutic management of ND is mainly based on systemic steroids in acute cases and immunosuppressive or immunomodulatory drugs in chronic forms. Underlying systemic conditions have to be diagnosed and treated as early as possible to avoid complications.
A Suppositional Theory of Conditionals
Authors: Carter Sam
Published: October 2020

Suppositional theories of conditionals take apparent similarities between supposition and conditionals as a starting point, appealing to features of the former to provide an account of the latter. This paper develops a novel form of suppositional theory, one which characterizes the relationship at the level of semantics rather than at the level of speech acts. In the course of doing so, it considers a range of novel data which shed additional light on how conditionals and supposition interact.
‘From the Totem to the Antenna’: Musique Concrète and the Universal at the end of the French Empire
Authors: Ridout Sam
Published: October 2020

This article situates Pierre Schaeffer’s musique concrète in the context of the end of the French empire. In drawing out conceptual continuities between Schaeffer’s administration of colonial radio in the mid-1950s and works of musique concrète from the same period, I argue that both projects are predicated on a commitment to the capacity of acousmatic listening to provide access to universal essences. The invocation of the ‘primitive’ in Schaeffer’s writing and music thus serves to buttress the universalizing rhetoric of musique concrète, portraying it as a neutral site for the reconciliation of different cultures, underwritten by a shared human essence. As such, musique concrète partakes in the logic of a colonial humanism, in which empire is conceived of as another such neutral framework. By way of conclusion, a form of acousmatic listening opposed to essence and empire is elaborated from the writings of Schaeffer’s anticolonial contemporaries.
H i study of isolated and paired galaxies: the MIR SFR-M⋆ sequence
Authors: Bok J , Skelton R E , Cluver M E , Jarrett T H , Jones M G , Verdes-Montenegro L
Published: October 2020

Using mid-infrared star formation rate and stellar mass indicators in WISE (Wide-field Infrared Survey Explorer), we construct and contrast the relation between star formation rate and stellar mass for isolated and paired galaxies. Our samples comprise a selection of AMIGA (Analysis of the interstellar Medium in Isolated GAlaxies; isolated galaxies) and pairs of ALFALFA (Arecibo Legacy Fast ALFA) galaxies with H i detections such that we can examine the relationship between H i content (gas fraction, H i deficiency) and galaxy location on the main sequence (MS) in these two contrasting environments. We derive for the first time an H i scaling relation for isolated galaxies using WISE stellar masses, and thereby establish a baseline predictor of H i content that can be used to assess the impact of environment on H i content when compared with samples of galaxies in different environments. We use this updated relation to determine the H i deficiency of both our paired and isolated galaxies. Across all the quantities examined as a function of environment in this work (MS location, gas fraction, and H i deficiency), the AMIGA sample of isolated galaxies is found to have the lower dispersion: σAMIGA = 0.37 versus σPAIRS = 0.55 on the MS, σAMIGA = 0.44 versus σPAIRS = 0.54 in gas fraction, and σAMIGA = 0.28 versus σPAIRS = 0.34 in H i deficiency. We also note fewer isolated quiescent galaxies, 3 (0.6${{\ \rm per\ cent}}$), compared to 12 (2.3${{\ \rm per\ cent}}$) quiescent pair members. Our results suggest the differences in scatter measured between our samples are environment driven. Galaxies in isolation behave relatively predictably, and galaxies in more densely populated environments adopt a more stochastic behaviour, across a broad range of quantities.
The completed SDSS-IV extended baryon oscillation spectroscopic survey: growth rate of structure measurement from anisotropic clustering analysis in configuration space between redshift 0.6 and 1.1 for the emission-line galaxy sample
Authors: Tamone Amélie , Raichoor Anand , Zhao Cheng , de Mattia Arnaud , Gorgoni Claudio , Burtin Etienne , Ruhlmann-Kleider Vanina , Ross Ashley J , Alam Shadab , Percival Will J , Avila Santiago , Chapman Michael J , Chuang Chia-Hsun , Comparat Johan , Dawson Kyle S , de la Torre Sylvain , du Mas des Bourboux Hélion , Escoffier Stephanie , Gonzalez-Perez Violeta , Hou Jiamin , Kneib Jean-Paul , Mohammad Faizan G , Mueller Eva-Maria , Paviot Romain , Rossi Graziano , Schneider Donald P , Wang Yuting , Zhao Gong-Bo
Published: October 2020

We present the anisotropic clustering of emission-line galaxies (ELGs) from the Sloan Digital Sky Survey IV (SDSS-IV) extended Baryon Oscillation Spectroscopic Survey (eBOSS) Data Release 16 (DR16). Our sample is composed of 173 736 ELGs covering an area of 1170 deg2 over the redshift range 0.6 ≤ z ≤ 1.1. We use the convolution Lagrangian perturbation theory in addition to the Gaussian streaming redshift space distortions to model the Legendre multipoles of the anisotropic correlation function. We show that the eBOSS ELG correlation function measurement is affected by the contribution of a radial integral constraint that needs to be modelled to avoid biased results. To mitigate the effect from unknown angular systematics, we adopt a modified correlation function estimator that cancels out the angular modes from the clustering. At the effective redshift, zeff = 0.85, including statistical and systematical uncertainties, we measure the linear growth rate of structure fσ8(zeff) = 0.35 ± 0.10, the Hubble distance $D_ H(z_{\rm eff})/r_{\rm drag} = 19.1^{+1.9}_{-2.1}$, and the comoving angular diameter distance DM(zeff)/rdrag = 19.9 ± 1.0. These results are in agreement with the Fourier space analysis, leading to consensus values of: fσ8(zeff) = 0.315 ± 0.095, $D_H(z_{\rm eff})/r_{\rm drag} = 19.6^{+2.2}_{-2.1}$, and DM(zeff)/rdrag = 19.5 ± 1.0, consistent with ΛCDM model predictions with Planck parameters.
How well can we determine ages and chemical abundances from spectral fitting of integrated light spectra?
Authors: Gonçalves Geraldo , Coelho Paula , Schiavon Ricardo , Usher Christopher
Published: October 2020

The pixel-to-pixel spectral fitting technique is often used in studies of stellar populations. It enables the user to infer several parameters from integrated light spectra such as ages and chemical abundances. In this paper, we examine the question of how the inferred parameters change with the choice of wavelength range used. We have employed two different libraries of integrated light spectra of globular clusters (GCs) from the literature and fitted them to stellar population models using the code Starlight. We performed tests using different regions of the spectra to infer reddening, ages, [Fe/H], and [α/Fe]. Comparing our results to age values obtained from isochrone fitting and chemical abundances from high-resolution spectroscopy, we find that: (1) the inferred parameters change with the wavelength range used; (2) the method in general retrieves good reddening estimates, specially when a wider wavelength range is fitted; (3) the ideal spectral regions for determination of age, [Fe/H], and [α/Fe] are 4170–5540, 5280–7020, and 4828–5364 Å, respectively; (4) the retrieved age values for old metal-poor objects can be several Gyr younger than those resulting from isochrone fitting. We conclude that, depending on the parameter of interest and the accuracy requirements, fitting the largest possible wavelength range may not necessarily be the best strategy.