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The homeless population experience significant inequalities in health, and there is an increasing appreciation of the potential of lifestyle factors in the development of neurodegenerative diseases, including Parkinson’s disease. We performed a study on the prevalence and distribution of pathological alpha-synuclein deposition throughout the central and peripheral nervous systems in a homeless population.
Methods:
Forty-four homeless individuals consecutively available for autopsy were recruited. Immunohistochemistry was performed using 5G4 antibody recognizing disease-associated forms of alpha-synuclein, complemented by phospho-synuclein antibody on autopsy tissues collected from 18 regions of the brain and spinal cord, as well as the right and left olfactory bulb, the cauda equina, the extramedullary portion of the vagus nerve, and 27 sites of peripheral organs.
Results:
The study cohort consisted of 38 males and 6 females, median age 58 years (range 32–67). Lewy-related pathology was present in the brains of three male cases. One showed Braak stage 2 (60 years old), and two stage 4 (56 and 59 years old). One of the Braak stage 4 cases had Lewy-related pathology in the spinal cord, the cauda equina, and the extramedullary portion of the vagus nerve. Examination of 27 sites of peripheral organs found that all three cases with Lewy-related pathology present in the brain were devoid of peripheral organ alpha-synuclein pathology. Multiple system-type alpha-synuclein pathology was not found.
Conclusion:
Our study, representing a snapshot of the homeless population that came to autopsy, suggests that alpha-synuclein pathology is prevalent in the homeless supporting further study of this vulnerable population.
To describe the development and initial experience of a clinical research program in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in Canada: The Rossy PSP Centre, to share the data acquisition tools adopted, and to report preliminary results.
Methods:
Extensive demographic and longitudinal clinical information is collected every 6 months using standardized forms. Biofluids are collected for biobanking and genetic analysis, and many patients are enrolled in neuroimaging research protocols. Brain donation is an important component of the program, and standardized processing protocols have been established, including very short death to autopsy times in patients undergoing medical assistance in dying.
Results:
Between Oct 2019 and Dec 2021, 132 patients were screened, 91 fulfilling criteria for PSP and 19 for CBS; age 71 years; 41% female; duration 5 years, age-of-onset 66 years. The most common symptoms at onset were postural instability and falls (45%), cognitive-behavioral changes (22%), and Parkinsonism (9%). The predominant clinical phenotype was Richardson syndrome (82%). Levodopa and amantadine resulted in partial and short-lasting benefit.
Conclusions:
The Rossy PSP Centre has been established to advance clinical and basic research in PSP and related tauopathies. The extent of the clinical data collected permits deep phenotyping of patients and allows for future clinical and basic research. Preliminary results showed expected distribution of phenotypes, demographics, and response to symptomatic treatments in our cohort. Longitudinal data will provide insight into the early diagnosis and management of PSP. Future steps include enrollment of patients in earlier stages, development of biomarkers, and fast-tracking well-characterized patients into clinical trials.
The past couple of decades have seen a substantial increase in linguistic research that highlights the non-arbitrariness of language, as manifested in motivated sound–meaning correspondences. Yet one of the challenges of such studies is that there is a relative paucity of data-driven analyses, especially in the case of languages other than English, such as Hungarian, even though the proportion of at least partially motivated words in Hungarian vocabulary is substantial. We address this gap by investigating the relationship between Hungarian phoneme classes and positive/negative sentiment based on 3,023 word forms retrieved from the Hungarian Sentiment Lexicon. Our results indicate that positive polarity word forms tend to contain more vowels, front vowels, continuants, fricatives, palatals, and sibilants. On the other hand, negative sentiment polarity words tend to have more rounded vowels, plosives, and dorsal consonants. While our analysis provides strong evidence for a set of non-arbitrary form–meaning relationships, effect sizes also reveal that such associations tend to be fairly weak tendencies, and therefore sentiment polarity cannot be derived from the relative frequencies of phoneme classes in a deterministic fashion.
Although the history of polycystic ovary syndrome (PCOS) was discussed in detail in Chapter 1, a brief review here is warranted. Stein and Leventhal were not only the first to describe the condition in 1934/5;[1] they also reported on a surgical treatment for anovulation, which resulted in two pregnancies. By 1964, Stein reported on a successful series of 108 anovulatory PCOS women treated by bilateral ovarian wedge resection (BOWR).[2]
Although the modern history of polycystic ovary syndrome (PCOS) started with the pivotal paper by Stein and Leventhal in 1935,[1] there are suggestions that the “syndrome” was referred to as early as in the time of Hippocrates (ca. 460–377 BC). Medical notes at the time referred to women “whose menstruation is less than three days or is meager, are robust, with a healthy complexion and a masculine appearance; yet they are not concerned about bearing children nor do they become pregnant” and suggest that they may have been describing women with PCOS.[2]
Polycystic ovary syndrome (PCOS) is one of the most common reproductive health problems of women, causing irregular periods and potential infertility amongst other challenging symptoms. Effective treatment remains a significant challenge and is largely achieved through hormonal medication and lifestyle changes. This third edition covers the aetiology, pathology, impact on fertility and effective medical and surgical management. The content has been thoroughly revised in line with updated guidelines and research developments in the field. A new chapter on the patient's perspective has been included, bringing valuable insight into the lived experience of the condition. Mood disorders and the psychological aspects of PCOS are also covered for the first time. This is a key reference for all clinicians involved in the care of patients with PCOS, including gynaecologists, IVF specialists and reproductive endocrinologists.
The term “polycystic ovary syndrome” (PCOS) has replaced the term Stein–Leventhal syndrome. Stein and Leventhal not only were the first to describe the condition but also developed and reported on a treatment, reporting on a successful series of 108 women treated by “wedge resection” [1]. In fact until the availability of clomiphene (clomifene) citrate (CC) in 1961 [2], this was the only option available to treat the infertility of women with this condition; characterized by obesity, oligomenorrhea, and anovulation. However, as treatment required laparotomy, and often resulted in periovarian adhesion formation, once medical treatment was available, initially CC, then human pituitary gonadotropins (hPG) [3], then urinary human menopausal gonadotropin (hMG) [4], wedge resection lost popularity, unless it was performed in conjunction with another surgical procedure that already required laparotomy.
Neurodegenerative diseases are a pathologically, clinically and genetically diverse group of disorders without effective disease-modifying therapies. Pathologically, these disorders are characterised by disease-specific protein aggregates in neurons and/or glia and referred to as proteinopathies. Many neurodegenerative diseases show pathological overlap with the same abnormally deposited protein occurring in anatomically distinct regions, which give rise to specific patterns of cognitive and motor clinical phenotypes. Sequential distribution patterns of protein inclusions throughout the brain have been described. Rather than occurring in isolation, it is increasingly recognised that combinations of one or more proteinopathies with or without cerebrovascular disease frequently occur in individuals with neurodegenerative diseases. In addition, complex constellations of ageing-related and incidental pathologies associated with tau, TDP-43, Aβ, α-synuclein deposition have been commonly reported in longitudinal ageing studies. This review provides an overview of current classification of neurodegenerative and age-related pathologies and presents the spectrum and complexity of mixed pathologies in community-based, longitudinal ageing studies, in major proteinopathies, and genetic conditions. Mixed pathologies are commonly reported in individuals >65 years with and without cognitive impairment; however, they are increasingly recognised in younger individuals (<65 years). Mixed pathologies are thought to lower the threshold for developing cognitive impairment and dementia. Hereditary neurodegenerative diseases also show a diverse range of mixed pathologies beyond the proteinopathy primarily linked to the genetic abnormality. Cases with mixed pathologies might show a different clinical course, which has prognostic relevance and obvious implications for biomarker and therapy development, and stratifying patients for clinical trials.
Coronavirus disease 2019 (COVID-19) is associated with autoimmunity and systemic inflammation. Patients with autoimmune rheumatic and musculoskeletal disease (RMD) may be at high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, based on evidence from the literature, as well as international scientific recommendations, we review the relationships between COVID-19, autoimmunity and patients with autoimmune RMDs, as well as the basics of a multisystemic inflammatory syndrome associated with COVID-19. We discuss the repurposing of pharmaceutics used to treat RMDs, the principles for the treatment of patients with autoimmune RMDs during the pandemic and the main aspects of vaccination against SARS-CoV-2 in autoimmune RMD patients.
We present novel methods for detecting lexical entailment in a fully rule-based and explainable fashion, by automatic construction of semantic graphs, in any language for which a crowd-sourced dictionary with sufficient coverage and a dependency parser of sufficient accuracy are available. We experiment and evaluate on both the Semeval-2020 lexical entailment task (Glavaš et al. (2020). Proceedings of the Fourteenth Workshop on Semantic Evaluation, pp. 24–35) and the SherLIiC lexical inference dataset of typed predicates (Schmitt and Schütze (2019). Proceedings of the 57th Annual Meeting of the Association for Computational Linguistics, pp. 902–914). Combined with top-performing systems, our method achieves improvements over the previous state-of-the-art on both benchmarks. As a standalone system, it offers a fully interpretable model of lexical entailment that makes detailed error analysis possible, uncovering future directions for improving both the semantic parsing method and the inference process on semantic graphs. We release all components of our system as open source software.
This is the essential textbook for students of obstetrics and gynaecology as well as women's health more generally. Thoroughly modern in approach, it covers clinical topics and surgical procedures as well as providing detailed commentary on the contemporary social, psychological and economic issues that affect women's health. Many authors who are the acknowledged leaders in their respective research field have contributed succinct chapters. In this way both students and health professionals are able to benefit from their expertise in a lively and accessible text. It will be a valuable resource for health professionals, including general practitioners, nurses, physiotherapists and health workers. Specific sections address women's mental health, genetics, prescribing for women, health promotion, hormones throughout the life cycle, psychological and behavioural issues. The text is fully illustrated with many useful guides, tables, photographs and diagrams.