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The diagnosis of neurodegenerative and psychiatric disorders (NPDs) in primary care can suffer from inefficiencies resulting in misdiagnoses and delayed diagnosis, limiting effective treatment options. The development of speech and language-based profiling biomarkers could aid in achieving earlier motor diagnosis for PD for instance, or more accurate diagnosis of clinically similar or late presenting NPDs.
RHAPSODY aims to investigate the feasibility of the remote administration of a battery of speech tasks in eliciting continuous narrative speech across a range of NPDs. The project also aims to determine the feasibility of using acoustic and linguistic biomarkers from speech data to support the clinical assessment and disambiguation of common NPDs
All participants (n=250) will take part in a single virtual telemedicine video conference with a researcher in which they are screened and complete a battery of speech tasks, in addition to cohort-specific screening measures. Over the following month, participants will be asked to complete a series of short, self-administered speech assessments via a smartphone application.
The speech tasks will be audio-recorded and analysed on Novoic’s technology platform. Objectives will be analysed using measures including average length of speech elicitation for speech tasks, intra- and inter-subject variance, differences in linguistic patterns, and response rates to speech assessments.
The analyses could help to identify and validate speech-derived clinical biomarkers to support clinicians in detecting and disambiguating between NPDs with heterogeneous presentations. This should further support earlier intervention, improved treatment options and improved quality of life.
In terms of significant financial interest and relationships, it is emphasised that the private organisation Novoic, who aim to develop speech algorithms for diagnostic use, is the study’s sponsor and employees or former employees of this company comprise
The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.
Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.
Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.
We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
This chapter reviews the major advances in autosomal recessive and autosomal dominant ataxias, discusses the use of genetic tests in these disorders, and summarizes some current ideas regarding pathogenesis. It also presents a list of the autosomal recessive ataxias that have been genotypically characterized to date. Mutations in ataxia with isolated vitamin E deficiency (AVED) are scattered throughout the gene and some of them may be associated with a mild phenotype, late onset, retinitis pigmentosa, and retained reflexes. A syndrome of ataxia associated with optic atrophy, visual loss, and cochlear degeneration has been mapped to chromosome. The spinocerebellar ataxia (SCAs) exhibits many phenotypic similarities so that it is almost impossible to diagnose the genotype from the phenotype alone. Many persons from families with ataxia will request predictive testing and occasionally prenatal testing. Disease-modifying therapies are under investigation and include antioxidants and drugs that may modify excitotoxicity or apoptosis.
Antibacterial drugs (oxytetracycline, streptomycin and sulphonamides) were included in the drinking water of healthy broiler chicks from the sixth to the twentieth day of life to select a resistant gut flora. On the twenty-first day the birds were divided into three groups and reared in separate rooms until 100 days of age. One group was housed in cages with wire floors while the others were reared on litter. Faeces from adult hens were added regularly to the litter of one of these groups to determine its effect on the gut flora of the chicks.
The ecology of Escherichia coli was studied using O-serotyping, biotyping and antibacterial drug resistogram typing. The proportion of E. coli in the dominant faecal flora resistant to two to four antibacterial drugs increased with time to reach a peak several days after the drugs were withdrawn. Thereafter, the level of drug resistance in the E. coli declined equally in all three groups. The majority of organisms with multiple resistance were derived from biotypes of O-serotypes initially resistant to only one drug and were identified before the drugs were administered. The decline in the level of resistance in the dominant faecal flora after the fourth week was due to the appearance of either new O-serotypes or new biotypes of O-serotypes previously shown to be multiply resistant, and which were either sensitive or resistant to only one drug. It is probable that these new strains were derived from the food since several O-serotypes appeared simultaneously in all three groups of birds.
An initial observation converning the failure of [3H]thymidine at high specific activity to be incorporated into the DNA of Crithidia fasciculata for more than a brief intitial period has been correlated with the presence at high specific activity in the organism of thymidine phosphorylase activity with an equilibrium in the direction of catabolism. This enzyme degrades thymidine to thymine which is not utilized by the organism. The enzyme has also been shown to be present in a number of other trypanosomatids, including the culture forms of Trypanosoma cruzi, where the specific activity was nearly as high as that in C. fasciculata.
Evidence is presented that in C. fasciculata, the culture forms of T. cruzi and possibly other species of trypanosomatid, the thymidine phosphorylase, together with a thymidylate phosphatase, forms a catabolic pathway which degrades thymine nucleotides to thymine, which is then excreated. About 60% of the thymine nucleotides made by organisms appear to be matabolized through the pathway, suggesting that their synthesis is not subject to completely effective regulatory control.
The genetics of a disease such as amyotrophic lateral sclerosis (ALS) require some flexibility in thinking about familiality compared with the genetics of isolated cases. About 10% of the time, an individual who develops ALS also has first-degree relatives who have been affected. For the remainder, the disease is said to be sporadic, but detailed investigation of the family tree may occasionally reveal that cousins or other more distant relatives have been affected. ALS can therefore be seen as a disease with an inheritance pattern that lies on a continuum from sporadic disease, to familial clustering to clear Mendelian familiality. For simplicity we have maintained the conventional separation of familial and sporadic disease, but as will become obvious, this distinction is largely artificial.
Familial ALS and the first descriptions
The concepts of genetics were coming into being at about the same time as the earliest descriptions of motor neuron diseases. Mendel presented his classic paper in 1865 (Mendel, 1865) in which he described his famous sweet pea hybridization experiments. He did not use the term gene or genetic to describe the heritable units but called them “formative elements.” Cambridge Professor of Biology William Bateson coined the term “genetics” (from the Greek “to generate”) in 1905 when applying for a university chair in a letter to the Cambridge zoologist, Adam Sedgwick. He wrote, “Such a word is badly wanted and if it were desirable to coin one, Genetics might do.”
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