bluuebunny/crossref_metadata_2025 huggingface dataset:
Manic syndromes in old age
Authors: Mussen Lauren , Vasudev Akshya
Published: February 2021

Manic syndromes in the elderly are different from those seen in the younger bipolar population. They are a heterogeneous group but can probably be divided into two main groups based on age of onset of the illness: late-onset bipolar disorder (LOB) and early-onset bipolar disorder (EOB). This chapter elaborates on differences in these two groups based on epidemiological data findings, clinical presentation, aetiopathogenesis, and management. It also discusses the latest concepts with regards to the vascular mania hypothesis, neuroimaging findings, and cognitive impairment in bipolar disorder (BD). It provides a critical review of pharmacological management options with reference to recently published data on mood stabilizers, antipsychotics, and antidepressant usage for this age group.
Sleep and circadian rhythm disorders
Authors: Anderson Kirstie , Xu Zheyu , Mosimann Urs , Boeve Bradley
Published: February 2021

This chapter reviews the most common sleep disorders in older adults and their treatment. It begins with a brief review of sleep physiology and then gives an outline on how to take a comprehensive sleep history. There are physiological sleep changes related to ageing, but sleep disorders are not part of normal ageing and are often associated with mental or physical disorders, pain, and neurodegenerative disease. The most common sleep disorders include insomnia, obstructive sleep apnoea, restless legs syndrome, REM sleep behaviour disorder, excessive daytime somnolence, and circadian rhythm disorders. An in-depth clinical history, including if possible, bed-partner’s information, is the key to diagnosis. Patients need to be informed about the physiological sleep changes and the principles of sleep hygiene. Many sleep disorders have effective therapies and patients will benefit from pharmacological and nonpharmacological treatment strategies.
Ethics and old age psychiatry
Authors: Hughes Julian C
Published: February 2021

This chapter is about ethics, i.e. about right or wrong decisions and good or bad judgments in clinical practice. It starts by reflecting on the extent to which all clinical decisions are, at one and the same time, ethical decisions. This is reflected in the idea of values-based practice. It outlines the major moral theories and a range of approaches to ethical issues. These theories and approaches have to be put into practice and it is not always clear how this should be done. The notion of patterns of practice, which will be described, may be helpful. There is a great variety of ethical issues that emerge in old age psychiatry, in particular in connection with dementia. The notion of patterns of practice is used, with the help of fictional vignettes, to discuss and understand such issues.
Mental capacity and decision-making
Authors: Emmett Charlotte , Hughes Julian C
Published: February 2021

This chapter takes the reader through the elements that make up mental capacity and underpin, therefore, decision-making. The provisions of the Mental Capacity Act 2005 (MCA) are considered in some detail, but the laws governing other jurisdictions in the UK are mentioned. It discusses the legal consequences of incapacity, both for the older person concerned and others, are considered and broader principles (e.g. to do with best interests) governing the use of restraint, deprivation of liberty, and support for decision making. Finally, we turn our attention to how international human rights legislation, and the international disability rights movement generally, increasingly shape the legal approach to capacity and decision making in the UK. The chapter ends, therefore, by considering the UN Convention on the Rights of Persons with Disabilities and the compatibility of the MCA with its provisions.
Ethics of living and dying with dementia
Authors: Hertogh Cees , de Boer Marike , Hendriks Simone
Published: February 2021

The gradual progression of dementia means there has to be a constant search for a reasonable balance between supporting autonomy and ensuring proper representation. Good end-of-life care for people with dementia depends on adequate advance care planning (ACP), starting early in the disease process. Where possible, it involves striving for joint decision-making with the patient and next-of-kin about (future) medical treatment and (future) care. Written advance directives may support representatives of incompetent patients in their role of surrogate decision maker, but the contents of the directive require interpretation in the context of ACP. The concept of ‘palliative care’ offers a (policy) framework for ACP as well as moral guideline for dealing with written advance directives of patients with dementia.
Carers and dementia
Authors: Oyebode Jan , Parveen Sahdia
Published: February 2021

Family carers are vitally important to sustaining the quality of people with dementia, providing over half of dementia care. This chapter reviews the experience of family carers and how they can be supported. Carers face many transitions as dementia develops but generally caring has a broad impact on carers’ lives, affecting fulfilment of needs in a range of ways both practical and relational. Caring carries burden and mental health consequences with around 30% carers becoming depressed, however, it also provokes gains and satisfactions. A number of models are available to assist understanding, focused on stress, appraisal and coping, grief, and positive aspects. A range of interventions including psycho-educational programmes, skills training, supportive counselling, cognitive behavioural therapies, and multi-component programmes can reduce carer stress. Interventions that are effective involve the person with dementia and the carer, are flexible enough to be individually tailored and are intensive or involve active participation.
Elder abuse
Authors: Manthorpe Jill
Published: February 2021

Old age psychiatrists will encounter situations of elder abuse in their practice. Whatever their work and professional policies they will need to think the unthinkable and to provide leadership to teams and across services. Asking and observing what is happening are key elements of their role. There is further need to work collaboratively to support older people at risk and to empower then by fostering or sustaining resilience. Old age psychiatrists can assist in prevention and in the building of supportive communities. They have a key role to play in furthering research and the creation of effective interventions for perpetrators. Their engagement with staff and residents in care homes may prevent poor practice and diminish opportunities for abuse and neglect.
The law relating to mental capacity and mental health
Authors: Wheat Kay
Published: February 2021

This chapter examines two key areas of law relating to medical treatment and care of those with mental disorder. The question of decision-making capacity is important for health care professionals, as well as other carers and agents dealing with older people. The law relating to this is covered by the Mental Capacity Act 2005 supplemented by previous case law where this is still relevant, and the key aspect of the law is the ability to treat people without capacity in their best interests. However, in the case of some patients, it may be necessary to use the Mental Health Act 1983. This legislation is focused, not on the capacity of the patient, but upon the effect that a mental disorder can have upon the patient risking damage to their own wellbeing, or to the wellbeing of others. The relationship between the two areas is not always clear.
Obstetrics
Authors: Goumalatsou Charlotte
Published: February 2021

This chapter in the Oxford Handbook of Clinical Specialties describes the obstetrics specialty, including antenatal care and screening. Medical conditions in pregnancy are investigated, including hyperemesis gravidarum, sickle-cell disease, cardiac disease, psychiatry, epilepsy, anaemia, HIV (human immunodeficiency virus), diabetes mellitus, thyroid disease, jaundice, malaria, renal disease, respiratory disease, connective tissue disease, hypertension, thromboprophylaxis, thrombophilia, and venous thromboembolism. Antenatal problems are explored, leading on to a discussion of labour and delivery, postnatal care, and obstetric emergencies.
Working with interpreters
Authors: Tribe Rachel
Published: February 2021

Psychiatrists will come into contact with service users who do not use English or the language of the country to which they have migrated. The professional responsibilities of all mental health professionals carry an obligation to serve all members of our communities equitably and impartially; this will include people who have migrated and are not fluent in the language of their chosen country of migration. Working with interpreters and cultural brokers can be an enriching and informative experience for psychiatrists, which can lead to the development of new knowledge. This is in addition to the challenging of what may be taken-for-granted knowledge, as well as the development of additional skills and ways of thinking about mental health. Interpreters and cultural brokers can, in addition to translating the language, explain relevant cultural factors, which are important to the clinical work and the meaning-making of service users and gain additional perspectives.
Separate or integrated services?
Authors: Bäärnhielm Sofie , Mösko Mike , Vaage Aina Basilier
Published: February 2021

In this chapter, we discuss the pros and cons of separate versus integrated services for immigrants and refugees. Our discussion is based on experiences from three high-income countries: Germany, Norway, and Sweden. All three, regardless of general public insurance systems covering healthcare costs, have barriers to mental health care for migrants and refugees. Additionally, their mental health care systems are unaccustomed to responding to cultural variety in patients’ expression of distress, explanatory models of illness, consequences of pre-migratory difficulties, and post-migratory adversities. Attention to post-traumatic stress and social determinants of mental health is also restricted. To bridge barriers and improve access to mental health care for immigrants and refugees, we will comment on the importance of adapting care, training of professionals, and outreach programmes. Also emphasized is the value of culturally sensitive mental health-promoting strategies to improve mental health literacy and reduce stigma among immigrants and refugees.
Specialist services
Authors: Varvin Sverre
Published: February 2021

Specialist services for asylum seekers and refugees have an important task in organizing prevention and treatment for vulnerable and affected groups. Specialist services for traumatized refugees must be developed as a discipline in itself and must be taught in basic training and for active professionals in all sectors of the healthcare system that serve refugees. Refugees have often multi-layered conditions with comorbidity, family problems, and social and relational problems. Families are often affected when members are traumatized and there is risk for transgenerational transmission of problems. What happens during flight and after resettlement is often crucial for traumatized refugees and this call for early interventions and chain of responses that secure continuity. Supporting development of resilience and resources in the family and the group is mandatory. A model for specialist services in a comprehensive approach is developed where specialist services such as psychotherapy have an important role.
An early intervention framework for the emotional health and well-being of unaccompanied minors
Authors: Draper Ana , Marcellino Elisa
Published: February 2021

Disturbed sleep patterns, semi-starvation symptoms, loss of hope, and trauma symptomatology are often co-occurring clinical concerns for professionals working with unaccompanied minors. Delivering mental health treatment in such a context can be extremely challenging owing to the complexity of this multiple presentation. The early intervention framework described in this chapter provides an innovative model of clinical work with unaccompanied minors who have experienced, and continue to experience, ongoing traumas. This intervention is distinct in that its focus is on developing and embedding a framework of competencies that can inform practice among different professionals involved. The chapter delineates four main interventions that are tools aimed to promote young people’s resilience and well-being.
Additional respiratory measurements
Authors: Kinnear William J.M. , Hull James H.
Published: February 2021

This chapter describes how additional information can be obtained during an exercise test to detect the airflow obstruction of exercise-induced asthma. The forced expiratory volume in one second (FEV1) may fall a few minutes after cessation of exercise, but this test is not particularly sensitive for detecting exercise-induced bronchoconstriction. The flow–volume loop during exercise can be compared with the pre-test maximal trace to detect expiratory airflow limitation. Addition of inspiratory capacity measurements can be helpful. The flow–volume loop may also suggest exercise-induced laryngeal obstruction, which can be confirmed by continuous fibreoptic laryngoscopy during exercise.
Confucianism, Taoism, and suicide
Authors: Fei Wu
Published: February 2021

In Confucianism, suicide is thought of as an acceptable way to protect one’s dignity and virtue: in late imperial China, suicide was required for intellectuals who had survived their emperor, and for women who had been raped. Nevertheless, most Confucian intellectuals do not consider suicide the best choice to pursue human virtue. Although Qu Yuan—the great poet and the person responsible for the most famous suicide in Chinese history—is often praised for his loyalty and virtues, he is also criticised for being narrow-minded. According to the Taoist teachings of Zhuangzi, one should not be too concerned about worldly affairs, including life and death. Examining ideas on life and death found in Confucianism and Taoism provides a deeper cultural understanding of possible underlying motives for committing suicide. This knowledge can contribute to more effective suicide prevention.
Recognizing a suicide crisis in psychiatric patients
Authors: Hendin Herbert
Published: February 2021

Data from therapists who were treating patients when they committed suicide were examined. Comparable information was obtained on depressed, non-suicidal patients treated by the same therapists. Three factors were identified as markers of a suicide crisis: precipitating events, changes in behaviour, and intense affective states. Of these, intense affective states appeared to be the most significant. The suicide patients had a significantly greater number of intense affects than did the comparison patients. The affect that most distinguished the two groups was desperation, which was intense in 30 of 36 (83%) of the suicide patients but in none of the comparison patients. The study permitted us to develop a scaled Affective States Questionnaire (ASQ) which is being tested prospectively.
Prevention of metropolitan and railway suicide
Authors: Ladwig Karl-Heinz , Erazo Natalia , Lukaschek Karoline
Published: February 2021

Railway suicides account for less than 10% of all suicides and are considered a major public health issue because of their consequences for the operation of the transportation system and their deteriorating impact on staff and bystanders. Behaviour patterns include jumping, lying, wandering, and deviant behaviour prodromal to the attempt. Case fatality is 90% of all attempts (railway) or circa 60% (metro). Victims are predominately male and young, with a median age stratum in the range of 25–34 years. The weekly distribution shows a peak at the beginning of the week and a low on weekends. Preventive measures include inhibiting access to the track (e.g. barriers at places of advanced risk or surveillance systems), inhibiting media coverage, or education of gatekeepers to increase awareness, and skilfulness in contact with vulnerable subjects. Railway suicide prevention is a realistic option; however, further research is urgently needed.
The Suicide Prevention Network of the European College of Neuropsychopharmacology (ECNP)
Authors: Wasserman Danuta , Carli Vladimir
Published: February 2021

The Suicide Prevention Network of the European College of Neuropsychopharmacology (ECNP) was initiated in 2009. The main objective of the network is to offer a platform for research collaboration to scientists in the field of suicidology. The network is funded by the ECNP with the purpose of supporting researchers in obtaining funding from the European Union. Over the years the Network on Suicide Prevention prepared and submitted several grant applications, and was successful in obtaining funding for the Horizon 2020 projects EDOR, NEVERMIND, and POTION. Moreover, the network has participated in several scientific initiatives that led to the publication of important systematic reviews in the field, as well as numerous workshops, symposia, and other scientific events.
Principles of health equity
Authors: Cookson Richard , Culyer Anthony J. , Norheim Ole F.
Published: February 2021

This chapter shows how informal normative concerns about health equity raised by decision makers can be translated into formal health equity objectives that are amenable to quantitative analysis using distributional cost-effectiveness analysis (DCEA). It also clarifies the kinds of ethical concerns that can and cannot be addressed by DCEA. Four ways of thinking about ethics are distinguished: value maximizing, moral rights, fair shares, and fair processes. When considering whether and how DCEA can be used to address a specific equity concern raised by decision makers, it is important to clarify which of these four ways of thinking underpins the concern. DCEA methods for evaluating distributions are based on the value maximizing way of thinking, but the information provided by DCEA about the distributional consequences of decisions can also help to address equity concerns relating to moral rights, fair shares, and fair processes.
Designing a distributional cost-effectiveness analysis
Authors: Cookson Richard , Griffin Susan , Norheim Ole F. , Culyer Anthony J.
Published: February 2021

This chapter is a guide to designing a distributional cost-effective analysis (DCEA) for research commissioners and producers. It describes the main components of DCEA and how they can be combined in different ways to inform decision-making in various contexts. The appropriate design of a DCEA will depend on the objectives of the relevant decision-making authorities; the political, economic, and institutional environment, and the prevailing social norms in the population being served; as well as the resources available for the analysis. We start by reviewing key questions about the decision-making context and illustrate how the answers to those questions can shape the study design, using our training example of nicotine replacement therapy in England. We then present the equity-efficiency impact plane, a visual tool for illustrating the relationship between the impact of a decision on efficiency (e.g. net health benefit) and equity (e.g. reduction in unfair health inequality). We then go through the main components of DCEA, including simple, low-cost forms of equity analysis that may be useful when detailed bespoke modelling of distributional consequences is not a practical option.
The abuse of psychiatry
Authors: Voren Robert van , Keukens Robert
Published: February 2021

Abuse of psychiatry was in the Soviet Union, for several decades, a State policy to quell dissent, and was carried out in collaboration with the then leadership of Soviet psychiatry. Approximately one-third of all political prisoners were subjected to this practice. The Soviet case has been taken as the main example. However, this branch of medicine has been misused elsewhere, in particular, in the Eastern Bloc in the 1980s, and in the People’s Republic of China in the late 1990s. Before World War II, on the pretext of setting up a merciful euthanasia programme, the Nazi regime made medical and nursing staff kill, by injection and gassing, tens of thousands of patients suffering from an incurable physical or mental illness. The chapter ends with thoughts on how the political abuse of psychiatry can be prevented.
Adjustment of therapy before/during pregnancy and lactation
Authors: Østensen Monika , Giles Ian
Published: February 2021

Treatment with medications during pregnancy and lactation is a challenge and needs to balance the risk of untreated maternal disease against any possible harm to the foetus or child. Indications for treatment are control of disease activity and ensuring a healthy pregnancy and healthy child outcomes. Administration of the following drugs is compatible with pregnancy: non-steroidal anti-inflammatory drugs (non-selective COX inhibitors until gestational week 32), glucocorticoids (preferentially at low dose), antimalarials, sulfasalazine, azathioprine (AZA), cyclosporine, tacrolimus, colchicine, and intravenous immunoglobulin. Methotrexate, mycophenolate mofetil, and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Among biologics tumour necrosis factor (TNF) inhibitors are best studied and appear reasonably safe preconceptionally, during pregnancy, and lactation; for other biologics foetal safety has not yet been established. The pregnancy compatibility of medications administered for comorbidities must be assessed. Except for cyclophosphamide other immunosuppressives are compatible with fatherhood.
Systemic lupus erythematosus and the risk of cardiovascular disease
Authors: Schreiber Karen , Jacobsen Søren
Published: February 2021

Women account for roughly 90% of patients with systemic lupus erythematosus (SLE) and they are typically diagnosed when they are in their childbearing age. Patients with SLE are at increased risk of premature cardiovascular disease (CVD) representing the major cause of morbidity and mortality in this patient group. Premature CVD is significantly pronounced in women with SLE who have a history of pre-eclampsia compared to those who have no history of pre-eclampsia. Therefore, the prevention of future CVD is particularly important in women with a previous pregnancy history complicated by pre-eclampsia. Patients worry about the possible risk for future CVD.
Rapid sorting of radio galaxy morphology using Haralick features
Authors: Ntwaetsile Kushatha , Geach James E
Published: February 2021

We demonstrate the use of Haralick features for the automated classification of radio galaxies. The set of thirteen Haralick features represent an extremely compact non-parametric representation of image texture, and are calculated directly from imagery using the Grey Level Co-occurrence Matrix (GLCM). The GLCM is an encoding of the relationship between the intensity of neighbouring pixels in an image. Using 10 000 sources detected in the first data release of the LOFAR Two-metre Sky Survey (LoTSS), we demonstrate that Haralick features are highly efficient, rotationally invariant descriptors of radio galaxy morphology. After calculating Haralick features for LoTSS sources, we employ the fast density-based hierarchical clustering algorithm hdbscan to group radio sources into a sequence of morphological classes, illustrating a simple methodology to classify and label new, unseen galaxies in large samples. By adopting a ‘soft’ clustering approach, we can assign each galaxy a probability of belonging to a given cluster, allowing for more flexibility in the selection of galaxies according to combinations of morphological characteristics and for easily identifying outliers: those objects with a low probability of belonging to any cluster in the Haralick space. Although our demonstration focuses on radio galaxies, Haralick features can be calculated for any image, making this approach also relevant to large optical imaging galaxy surveys.
Brassica carinata genome characterization clarifies U’s triangle model of evolution and polyploidy in Brassica
Authors: Song Xiaoming , Wei Yanping , Xiao Dong , Gong Ke , Sun Pengchuan , Ren Yiming , Yuan Jiaqing , Wu Tong , Yang Qihang , Li Xinyu , Nie Fulei , Li Nan , Feng Shuyan , Pei Qiaoying , Yu Tong , Zhang Changwei , Liu Tongkun , Wang Xiyin , Yang Jinghua
Published: February 2021

Ethiopian mustard (Brassica carinata) in the Brassicaceae family possesses many excellent agronomic traits. Here, the high-quality genome sequence of B. carinata is reported. Characterization revealed a genome anchored to 17 chromosomes with a total length of 1.087 Gb and an N50 scaffold length of 60 Mb. Repetitive sequences account for approximately 634 Mb or 58.34% of the B. carinata genome. Notably, 51.91% of 97,149 genes are confined to the terminal 20% of chromosomes as a result of the expansion of repeats in pericentromeric regions. Brassica carinata shares one whole-genome triplication event with the five other species in U’s triangle, a classic model of evolution and polyploidy in Brassica. Brassica carinata was deduced to have formed ∼0.047 Mya, which is slightly earlier than B. napus but later than B. juncea. Our analysis indicated that the relationship between the two subgenomes (BcaB and BcaC) is greater than that between other two tetraploid subgenomes (BjuB and BnaC) and their respective diploid parents. RNA-seq datasets and comparative genomic analysis were used to identify several key genes in pathways regulating disease resistance and glucosinolate metabolism. Further analyses revealed that genome triplication and tandem duplication played important roles in the expansion of those genes in Brassica species. With the genome sequencing of B. carinata completed, the genomes of all six Brassica species in U’s triangle are now resolved. The data obtained from genome sequencing, transcriptome analysis, and comparative genomic efforts in this study provide valuable insights into the genome evolution of the six Brassica species in U’s triangle.
Efficacy and Safety of Phenobarbitone as First-Line Treatment for Neonatal Seizure: A Systematic Review and Meta-Analysis
Authors: Kumar Jogender , Meena Jitendra , Yadav Jaivinder , Saini Lokesh
Published: February 2021

Background and objective

Phenobarbitone is used as a first-line drug for neonatal seizures. However, its poor short- and long-term safety profile is concerning. We aim to systematically synthesize the data on the efficacy and safety of phenobarbitone as a first-line agent and compare it against other anti-epileptic drugs (AEDs) in neonates.

Methods

Using keywords related to the study population (neonatal seizure) and intervention (phenobarbitone), we searched CENTRAL, Embase, PubMed and Web of Science until 15 December 2020. Randomized controlled trials (RCTs) comparing phenobarbitone with any other AED as first-line therapy for seizure control in the neonates were considered eligible. The random-effect meta-analysis was done using RevMan 5.3 software.

Results

We screened through 443 records and identified nine eligible studies (719 participants). Five RCTs comparing phenobarbitone with levetiracetam did not find any difference in seizure control with the first dose [risk ratio (RR) 1.43, 95% CI 0.79–2.57] or adverse effects (RR 4.66; 95% CI 0.33–65.83). Two trials comparing phenobarbitone and phenytoin also did not find any difference in seizure control with the first dose (RR 2.09; 95% CI 0.31–14.03) and other outcomes. Only one RCT compared phenobarbitone and lorazepam and found lorazepam to be more efficacious in seizure control with the first dose (RR 0.71; 95% CI 0.53–0.94). Three trials compared neurodevelopmental outcomes, in which levetiracetam was better in two, whereas one did not find any difference.

Conclusion

Phenobarbitone is at least as efficacious and safe as other drugs like phenytoin and levetiracetam. The data over the long-term neurodevelopmental outcome are lacking. The existing evidence is insufficient to recommend other drugs over phenobarbitone.
Genotyping and differential bacterial inhibition of Batrachochytrium dendrobatidis in threatened amphibians in Costa Rica
Authors: Abarca Juan G. , Whitfield Steven M. , Zuniga-Chaves Ibrahim , Alvarado Gilbert , Kerby Jacob , Murillo-Cruz Catalina , Pinto-Tomás Adrián A.
Published: February 2021

Amphibians have declined around the world in recent years, in parallel with the emergence of an epidermal disease called chytridiomycosis, caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd). This disease has been associated with mass mortality in amphibians worldwide, including in Costa Rica, and Bd is considered an important contributor to the disappearance of this group of vertebrates. While many species are susceptible to the disease, others show tolerance and manage to survive infection with the pathogen. We evaluated the pathogen Bd circulating in Costa Rica and the capacity of amphibian skin bacteria to inhibit the growth of the pathogen in vitro. We isolated and characterized – genetically and morphologically – several Bd isolates from areas with declining populations of amphibians. We determined that the circulating chytrid fungus in Costa Rica belongs to the virulent strain Bd-GPL-2, which has been related to massive amphibian deaths worldwide; however, the isolates obtained showed genetic and morphological variation. Furthermore, we isolated epidermal bacteria from 12 amphibian species of surviving populations, some in danger of extinction, and evaluated their inhibitory activity against the collection of chytrid isolates. Through bioassays we confirmed the presence of chytrid-inhibitory bacterial genera in Costa Rican amphibians. However, we observed that the inhibition varied between different isolates of the same bacterial genus, and each bacterial isolation inhibited fungal isolation differently. In total, 14 bacterial isolates belonging to the genera

Stenotrophomonas

,

Streptomyces

,

Enterobacter

,

Pseudomonas

and

Klebsiella

showed inhibitory activity against all Bd isolates. Given the observed variation both in the pathogen and in the bacterial inhibition capacity, it is highly relevant to include local isolates and to consider the origin of the microorganisms when performing in vivo infection tests aimed at developing and implementing mitigation strategies for chytridiomycosis.
Birhan Maternal and Child Health cohort: a study protocol
Authors: Chan Grace J. , Hunegnaw Bezawit Mesfin , Van Wickle Kimiko , Mohammed Yahya , Hunegnaw Mesfin , Goddard Frederick G. B. , Tadesse Fisseha , Bekele Delayehu
Published: February 2021

Introduction

Reliable estimates on maternal and child morbidity and mortality are essential for health programs and policies. Data are needed in populations which have the highest burden of disease but also have the least evidence and research, to design and evaluate health interventions to prevent illnesses and deaths that occur worldwide each year.

Methods and analysis

The Birhan Maternal and Child Health (MCH) cohort is an open prospective pregnancy and birth cohort nested within the Birhan health and demographic surveillance system (HDSS). An estimated 2500 pregnant women are enrolled each year and followed through pregnancy, birth, and the postpartum period. Newborns are followed through two years of life to assess growth and development. Baseline medical data, signs and symptoms, laboratory test results, anthropometrics, and pregnancy and birth outcomes (stillbirth, preterm birth, low birthweight) are collected from both home and health facility visits. We will calculate the period prevalence and incidence of primary morbidity and mortality outcomes.

Ethics and Dissemination

The cohort has received ethical approval. Findings will be disseminated at scientific conferences, peer-reviewed journals, and to relevant stakeholders including the ministry of health.

Strengths and limitations of this study

This cohort collects longitudinal data at multiple time points from pregnancy through birth and childhood in a setting where there are limited data.

Data from this study provide estimates for birth outcomes such as stillbirths, preterm birth, and low birth weight.

Results will inform risk profiles for maternal, neonatal, and child morbidity and mortality.

Similar to all observational studies, there are potential confounders that are unmeasurable.

Evidence from this study will support policies and programs to improve maternal and child health.
Impact of the Clinical Trials Act on noncommercial clinical research in Japan: An interrupted time-series analysis
Authors: Tsutsumi Ikuyo , Tsutsumi Yusuke , Yoshida Chikashi , Komeno Takuya , Imanaka Yuichi
Published: February 2021

Background

The number of new noncommercial clinical studies conducted in Japan declined within the first year of the implementation of the Clinical Trials Act (CTA) on April 1, 2018. This study aimed to examine the impact of the CTA’s enforcement on the number of new noncommercial clinical studies registered in the Japanese Clinical Trial Registry.

Methods

An interrupted time-series design was used in the analysis, which was conducted for the period of April 2015 to March 2019. We collected data for trials registered in the Clinical Trial Registry, managed by the University Hospital Medical Information Network.

Results

In total, 35,811 studies were registered in the registry; of these, 16,455 fulfilled the eligibility criteria. The difference in the trend of monthly number of new trials after CTA enforcement decreased significantly by 15.0 trials (95% CI, −18.7 to −11.3), and the level decreased by 40.8 (95% CI, −68.2 to −13.3) from the pre-enforcement to the post-enforcement period. Multigroup analyses indicated that the act exerted a significant effect on the trend of new clinical trials, particularly those with smaller sample sizes, interventional study designs, and nonprofit funding sponsors.

Conclusions

The number of Japanese noncommercial clinical studies declined significantly following implementation of the CTA. It is necessary to establish a system to promote clinical studies in Japan while ensuring transparency and safety.
Updated SARS-CoV-2 Single Nucleotide Variants and Mortality Association
Authors: Fang Shuyi , Liu Sheng , Shen Jikui , Lu Alex Z , Zhang Yucheng , Li Kailing , Liu Juli , Yang Lei , Hu Chang-Deng , Wan Jun
Published: February 2021

Since its outbreak in December 2019, COVID-19 has caused 100,5844,555 cases and 2,167,313 deaths as of Jan 27, 2021. Comparing our previous study of SARS-CoV-2 single nucleotide variants (SNVs) before June 2020, we found out that the SNV clustering had changed considerably since June 2020. Apart from that the group SNVs represented by two non-synonymous mutations A23403G (S: D614G) and C14408T (ORF1ab: P4715L) became dominant and carried by over 95% genomes, a few emerging groups of SNVs were recognized with sharply increased monthly occurrence ratios up to 70% in November 2020. Further investigation revealed that several SNVs were strongly associated with the mortality, but they presented distinct distribution in specific countries, e.g., Brazil, USA, Saudi Arabia, India, and Italy. SNVs including G25088T, T25A, G29861T and G29864A were adopted in a regularized logistic regression model to predict the mortality status in Brazil with the AUC of 0.84. Protein structure analysis showed that the emerging subgroups of non-synonymous SNVs and those mortality-related ones in Brazil were located on protein surface area. The clashes in protein structure introduced by these mutations might in turn affect virus pathogenesis through conformation changes, leading to the difference in transmission and virulence. Particularly, we found that SNVs tended to occur in intrinsic disordered regions (IDRs) of Spike (S) and ORF1ab, suggesting a critical role of SNVs in protein IDRs to determine protein folding and immune evasion.
Innate visual attraction in wood ants is a hardwired behavior seen across different motivational and ecological contexts
Authors: Buehlmann Cornelia , Graham Paul
Published: February 2021

Ants are expert navigators combining innate and learnt navigational strategies. Whereas we know that the ants’ feeding state segregates visual navigational memories in ants navigating along a learnt route, it is an open question if the motivational state also affects the ants’ innate visual preferences. Wood ant foragers show an innate attraction to conspicuous visual cues. These foragers inhabit cluttered woodland habitat and feed on honeydew from aphids on trees, hence, the attraction to ‘tree-like’ objects might be an ecologically relevant behavior that is tailored to the wood ants’ foraging ecology. Foragers from other ant species with different foraging ecologies show very different innate attractions. We investigated here the innate visual response of wood ant foragers with different motivational states, i.e., unfed or fed, as well as males that show no foraging activity. Our results show that ants from all three groups orient towards a prominent visual cue, i.e., this intrinsic visuomotor response is not context dependent, but a hardwired behavior seen across different motivational and ecological contexts.
Architecture and evolution of subtelomeres in the unicellular green algaChlamydomonas reinhardtii
Authors: Chaux-Jukic Frédéric , O’Donnell Samuel , Craig Rory J. , Eberhard Stephan , Vallon Olivier , Xu Zhou
Published: February 2021

In most eukaryotes, subtelomeres are dynamic genomic regions populated by multi-copy sequences of different origins, which can promote segmental duplications and chromosomal rearrangements. However, their repetitive nature has complicated the efforts to sequence them, analyze their structure and infer how they evolved. Here, we use recent and forthcoming genome assemblies ofChlamydomonas reinhardtiibased on long-read sequencing to comprehensively describe the subtelomere architecture of the 17 chromosomes of this model unicellular green alga. We identify three main repeated elements present at subtelomeres, which we callSultan,SubtileandSuber, alongside three chromosome extremities with ribosomal DNA as the only identified component of their subtelomeres. The most common architecture, present in 27 out of 34 subtelomeres, is an array of 1 to 46 tandem copies ofSultanelements adjacent to the telomere and followed by a transcribed centromere-proximalSpacersequence, a G-rich microsatellite and a region rich in transposable elements. Sequence similarity analyses suggest thatSultanelements underwent segmental duplications within each subtelomere and rearranged between subtelomeres at a much lower frequency. Comparison of genomic sequences of three laboratory strains and a wild isolate ofC. reinhardtiishows that the overall subtelomeric architecture was already present in their last common ancestor, although subtelomeric rearrangements are on-going at the species level. Analysis of other green algae reveals the presence of species-specific repeated elements, highly conserved across subtelomeres and unrelated to theSultanelement, but with a subtelomere structure similar toC. reinhardtii. Overall, our work uncovers the complexity and evolution of subtelomere architecture in green algae.
Single-cell sequencing reveals clonally expanded plasma cells during chronic viral infection produce virus-specific and cross-reactive antibodies
Authors: Neumeier Daniel , Pedrioli Alessandro , Genovese Alessandro , Sandu Ioana , Ehling Roy , Hong Kai-Lin , Papadopoulou Chrysa , Agrafiotis Andreas , Kuhn Raphael , Robbiani Damiano , Han Jiami , Hauri Laura , Csepregi Lucia , Greiff Victor , Merkler Doron , Reddy Sai T. , Oxenius Annette , Yermanos Alexander
Published: February 2021

Plasma cells and their secreted antibodies play a central role in the long-term protection against chronic viral infection. However, due to experimental limitations, a comprehensive description of linked genotypic, phenotypic, and antibody repertoire features of plasma cells (gene expression, clonal frequency, virus specificity, and affinity) has been challenging to obtain. To address this, we performed single-cell transcriptome and antibody repertoire sequencing of the murine bone marrow plasma cell population following chronic lymphocytic choriomeningitis virus infection. Our single-cell sequencing approach recovered full-length and paired heavy and light chain sequence information for thousands of plasma cells and enabled us to perform recombinant antibody expression and specificity screening. Antibody repertoire analysis revealed that, relative to protein immunization, chronic infection led to increased levels of clonal expansion, class-switching, and somatic variants. Furthermore, antibodies from the highly expanded and class-switched (IgG) plasma cells were found to be specific for multiple viral antigens and a subset of clones exhibited cross-reactivity to non-viral- and auto-antigens. Integrating single-cell transcriptome data with antibody specificity suggested that plasma cell transcriptional phenotype was correlated to viral antigen specificity. Our findings demonstrate that chronic viral infection can induce and sustain plasma cell clonal expansion, combined with significant somatic hypermutation, and can generate cross-reactive antibodies.

Graphical abstract.

Single-cell sequencing reveals clonally expanded plasma cells during chronic viral infection produce virus-specific and cross-reactive antibodies.
DIAmeter: Matching peptides to data-independent acquisition mass spectrometry data
Authors: Lu Yang Young , Bilmes Jeff , Rodriguez-Mias Ricard A , Villén Judit , Noble William Stafford
Published: February 2021

Tandem mass spectrometry data acquired using data independent acquisition (DIA) is challenging to interpret because the data exhibits complex structure along both the mass-to-charge (m/z) and time axes. The most common approach to analyzing this type of data makes use of a library of previously observed DIA data patterns (a “spectral library”), but this approach is expensive because the libraries do not typically generalize well across laboratories. Here we propose DIAmeter, a search engine that detects peptides in DIA data using only a peptide sequence database. Unlike other library-free DIA analysis methods, DIAmeter supports data generated using both wide and narrow isolation windows, can readily detect peptides containing post-translational modifications, can analyze data from a variety of instrument platforms, and is capable of detecting peptides even in the absence of detectable signal in the survey (MS1) scan.
Quantitative prediction of conditional vulnerabilities in regulatory and metabolic networks ofMycobacterium tuberculosis
Authors: Immanuel Selva Rupa Christinal , Arrieta-Ortiz Mario L. , Ruiz Rene A. , Pan Min , de Lomana Adrian Lopez Garcia , Peterson Eliza J. R. , Baliga Nitin S.
Published: February 2021

The ability ofMycobacterium tuberculosis(Mtb) to adopt heterogeneous physiological states, underlies its success in evading the immune system and tolerating antibiotic killing. Drug tolerant phenotypes are a major reason why the tuberculosis (TB) mortality rate is so high, with over 1.8 million deaths annually. To develop new TB therapeutics that better treat the infection (faster and more completely), a systems-level approach is needed to reveal the complexity of network-based adaptations of Mtb. Here, we report a new predictive model called PRIME (Phenotype ofRegulatory influencesIntegrated withMetabolism andEnvironment) to uncover environment-specific vulnerabilities within the regulatory and metabolic networks of Mtb. Through extensive performance evaluations using genome-wide fitness screens, we demonstrate that PRIME makes mechanistically accurate predictions of context-specific vulnerabilities within the integrated regulatory and metabolic networks of Mtb, accurately rank-ordering targets for potentiating treatment with frontline drugs.
Dysregulation of PAX5 causes uncommitted B cell development and tumorigenesis in mice
Authors: Boast Brigette , Helian Kaiyue , Andrews T. Daniel , Li Xi , Cho Vicky , Closa Adria , Sutton Henry J. , Reed Joanne H. , Bergmann Hannes , Roots Carla M. , Yabas Mehmet , Barthel Nadine , Omari Sofia A. , Young Clara , Miosge Lisa A. , Eyras Eduardo , Nutt Stephen L. , Hein Nadine , Hannan Katherine M. , Cockburn Ian A. , Goodnow Christopher C. , Enders Anselm
Published: February 2021

PAX5 is the master transcription factor controlling B cell identity. In humans, mutations inPAX5account for 30% of B cell acute lymphoblastic leukemia (B-ALL) cases. Investigating the causal effects ofPAX5mutations has however been difficult due to the premature lethality ofPax5−/−mice. Here we describe a novel mouse strain with a premature STOP mutation inPax5(Y351*) that produces a truncated protein and reduction in protein function, yet still allows for some B cell development to occur. A population of uncommitted and multipotent CD19+B220−B cells develops in the bone marrow of homozygous mice leading to the development of B-ALL. We show that the tumors frequently acquire secondary mutations inJak3, andPtpn11highlighting key pathways interacting with PAX5 during malignant transformation. Analysis of the PAX5Y351*mice provide insight not only into the functional consequence of reduced PAX5 activity on B cell development and identity, but also provides an avenue in which to study PAX5-driven B-ALL in mice.

One Sentence Summary

Reduction in PAX5 function in mice induces the development of uncommitted B cells that have multipotent and malignant potential.
Non cell-autonomous effect of astrocytes on cerebral cavernous malformations
Authors: Lopez-Ramirez Miguel Alejandro , Soliman Shady Ibrahim , Hale Preston , Lai Catherine Chinhchu , Pham Angela , Estrada Esau , McCurdy Sara , Girard Romuald , Verma Riya , Moore Thomas , Lightle Rhonda , Hobson Nicholas , Shenkar Robert , Poulsen Orit , Haddad Gabriel G. , Daneman Richard , Gongol Brendan , Sun Hao , Lagarrigue Frederic , Awad Issam A. , Ginsberg Mark H.
Published: February 2021

Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in one of three genes, includingKRIT1(CCM1),CCM2, andPDCD10(CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we report that proliferative astrocytes play a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2 and KLF4-dependent elevation of eNOS in CCM endothelium. The increased brain endothelial production of NO stabilizes HIF-1α in astrocytes, resulting in increased VEGF production and expression of a “hypoxic” program under normoxic conditions. We show that the upregulation of cyclooxygenase-2 (COX-2), a direct HIF-1α target gene and a known component of the hypoxic program, contributes to the development of CCM lesions because the administration of a COX-2 inhibitor significantly prevents progression of CCM lesions. Thus, non-cell-autonomous crosstalk between CCM endothelium and astrocytes propels vascular lesion development, and components of the hypoxic program represent potential therapeutic targets for CCMs.
A Mixture Model Incorporating Individual Heterogeneity in Human Lifetimes
Authors: Huang Fei , Maller Ross , Milholland Brandon , Ning Xu
Published: February 2021

Analysis of some extensive individual-record data using a demographically informed model suggests constructing a general population model in which the lifetime of a person, beyond a certain threshold age, follows an extreme value distribution with a finite upper bound, and with that upper bound randomized over the population. The resulting population model incorporates heterogeneity in life-lengths, with lifetimes being finite individually, but with extremely long lifespans having negligible probability. Our findings are compared in detail with those of related studies in the literature, and used to reconcile contradictions between previous studies of extreme longevity. While being consistent with currently reported analyses of human lifetimes, we nevertheless differ with those who conclude in favour of unbounded human lifetimes.