Screening for Autism Spectrum Condition Through Inner City Homeless Services in the Republic of Ireland.

Homeless service users were screened for autism spectrum disorder through one of Ireland's leading not for profit service providers. Keyworkers acted as proxy informants; their caseloads were screened using the DSM-5-Autistic Traits in the Homeless Interview (DATHI). Client current and historical health and behaviour data was collated. A representative sample of 106 eligible keyworkers caseloads were screened, identifying 3% "present" and 9% "possibly present" for autistic traits with the DATHI. These findings suggest a high estimate of autism prevalence and support emerging evidence that, people with autism are overrepresented in the homeless population, compared to housed populations. Autism may be a risk factor for entry into homelessness and a challenge to exiting homeless and engaging with relevant services.

Very Long-Chain Acyl-CoA Dehydrogenase Deficiency Presenting as Rhabdomyolysis.

Presentation A 20 year old female attended the Emergency Department by ambulance following a collapse at a concert. On arrival she was complaining of generalised muscular pain. She had not eaten for over 12 hours and had been dancing for approximately 6 hours. The patient was known to have Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD). She had a normal exam, and normal vital signs. Diagnosis A diagnosis of rhabdomyolysis was made after her creatinine kinase (CK) was found to be >100000 units/litre (Normal range < 170U/L). Her urine was dark brown with urinalysis positive for blood. Treatment The patient was admitted to the high dependency unit, where she was treated with intravenous fluids. Her urine output and renal function were closely monitored. She made a full recovery and was discharged home four days later. Conclusion (VLCAD) is an inherited, autosomal recessive, metabolic disorder caused by mutations in the ACADVL gene. Management includes treatment of manifestation, primary prevention of manifestation, and prevention of secondary complications.

Counseling clients during New York City's COVID-19 pandemic: observations on fundamental elements of emotions management.

New York City is in the grip of the COVID-19 pandemic. Health care centers are stretched beyond capacity. Daily death rates are staggering. The city's population is hunkered down in fear. Our anxiety treatment center is treating patients via video appointments. We are helping anxious individuals adapt to tumultuous changes that we ourselves are experiencing. Our work in this time has reinforced our core beliefs about managing one's emotions; that difficult times require more active coping and that we all draw heavily from social support and familiarity to create a feeling of well-being. These principles and the experiences of our patients are discussed.

Site-Specific and Temporal Effects of Apraglutide, a Novel Long-Acting Glucagon-Like Peptide-2 Receptor Agonist, on Intestinal Growth in Mice.

Long-acting glucagon-like peptide-2 receptor (GLP-2R) agonists are well-established to increase intestinal growth in rodents and, most notably, humans with short bowel syndrome. Most of the trophic effects of GLP-2R agonists are reported to be mediated through increased growth of the crypt-villus axis, resulting in enhanced mucosal mass and improved intestinal function. The present study examined the effects of apraglutide, a novel GLP-2R agonist, on the growth of the small intestine and colon after 3, 7, and 10 weeks of treatment in male and female mice. Apraglutide (3 mg/kg; three times per week) significantly increased small intestinal weight (P < 0.001) and length (P < 0.001) after 3 weeks of administration, with a further increase in effectiveness after 10 weeks (P < 0.01). Crypt depth and villus height were both markedly increased after 3 weeks of apraglutide administration (P < 0.001) but did not show any further increase with duration of treatment, whereas crypt number and intestinal circumference were increased after 7 and 10 weeks (P < 0.01) but not after 3 weeks of apraglutide treatment. Both the weight and the length of the colon were also enhanced by apraglutide treatment for 3 weeks (P < 0.001), and these effects were maintained but did not improve further with continued apraglutide administration. The results of this study demonstrate that the novel, long-acting GLP-2R agonist, apraglutide, demonstrates an unexpected marked ability to increase intestinal length as well as exert time- and location-dependent specificity in its intestinotrophic actions. SIGNIFICANCE STATEMENT: The novel long-acting glucagon-like peptide 2 receptor agonist, apraglutide, enhances intestinal weight as well as intestinal length in a time- and site-dependent fashion.

The dental management of a mouth cancer patient.

Dentists and dental care professionals have a key role to play in the journey of the mouth cancer patient. Involved in the prevention, diagnosis and delivery of oral healthcare before, during and following mouth cancer treatment, dental professionals are essential to the delivery of patient care. This article will explore and consider the priorities of dental pre-assessment and the subsequent delivery of oral healthcare in the context of the different oncology treatment strategies utilised and in end-of-life care. The significant side effects of radiotherapy will be reviewed and clinical dental considerations presented using the existing evidence base and available guidelines. Ensuring mouth cancer does not result in dental disease is an important role for all members of the dental community.

The effects of 100% wild blueberry (Vaccinium angustifolium) juice consumption on cardiometablic biomarkers: a randomized, placebo-controlled, crossover trial in adults with increased risk for type 2 diabetes.

BACKGROUND: Wild blueberries have a high content of polyphenols, but there is limited data evaluating their health benefits in adults at risk for type 2 diabetes. The objective of the study was to investigate whether consumption of 100% wild blueberry juice improves cardiometabolic biomarkers associated with type 2 diabetes risk. METHODS: A single-blind, randomized, placebo-controlled, crossover design trial was conducted in which adults (women, n = 19, ages 39-64 y) at risk for type 2 diabetes consumed 240 mL of wild blueberry juice or a placebo beverage as part of their free-living diet for 7 days. Blood was collected to determine various biomarkers such as fasting plasma glucose, fasting serum insulin, surrogate markers of insulin sensitivity, triglycerides, inflammation (interleukin-6, interleukin-10, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, serum amyloid A), adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1), oxidative stress (LDL-oxidation, total 8-isoprostanes), and nitric oxide. Endothelial function and blood pressure were also assessed. RESULTS: Wild blueberry juice consumption for 7 days produced no significant changes in glucose, insulin, insulin sensitivity, triglycerides, inflammatory markers, adhesion molecules, oxidative stress, endothelial function or blood pressure. However, wild blueberry juice consumption showed a trend for lowering systolic blood pressure: 120.8 ± 2.2 mmHg in the placebo group vs 116.0 ± 2.2 mmHg in the blueberry juice group (P = 0.088). Serum concentrations of nitrates and nitrites, an index of nitric oxide production, increased from 2.9 ± 0.4 µM after placebo drink to 4.1 ± 0.4 µM after drinking wild blueberry juice (P = 0.039). CONCLUSIONS: Short-term consumption of wild blueberry juice may promote cardioprotective effects, by improving systolic blood pressure, possibly through nitric oxide production, in adults at risk for type 2 diabetes. This outcome warrants longer-term human studies of blueberries, including defined amounts of either the whole fruit or juice, to clarify whether polyphenol-rich foods can be efficacious for improving cardiometabolic biomarkers in adults at risk for type 2 diabetes. TRIAL REGISTRATION: NCT02139878, clinicaltrials.gov; date of registration: May 4, 2014.

Effects of maltreatment and parental schizophrenia spectrum disorders on early childhood social-emotional functioning: a population record linkage study.

AIMS: Childhood maltreatment and a family history of a schizophrenia spectrum disorder (SSD) are each associated with social-emotional dysfunction in childhood. Both are also strong risk factors for adult SSDs, and social-emotional dysfunction in childhood may be an antecedent of these disorders. We used data from a large Australian population cohort to determine the independent and moderating effects of maltreatment and parental SSDs on early childhood social-emotional functioning. METHODS: The New South Wales Child Development Study combines intergenerational multi-agency data using record linkage methods. Multiple measures of social-emotional functioning (social competency, prosocial/helping behaviour, anxious/fearful behaviour; aggressive behaviour, and hyperactivity/inattention) on 69 116 kindergarten children (age ~5 years) were linked with government records of child maltreatment and parental presentations to health services for SSD. Multivariable analyses investigated the association between maltreatment and social-emotional functioning, adjusting for demographic variables and parental SSD history, in the population sample and in sub-cohorts exposed and not exposed to parental SSD history. We also examined the association of parental SSD history and social-emotional functioning, adjusting for demographic variables and maltreatment. RESULTS: Medium-sized associations were identified between maltreatment and poor social competency, aggressive behaviour and hyperactivity/inattention; small associations were revealed between maltreatment and poor prosocial/helping and anxious/fearful behaviours. These associations did not differ greatly when adjusted for parental SSD, and were greater in magnitude among children with no history of parental SSD. Small associations between parental SSD and poor social-emotional functioning remained after adjusting for demographic variables and maltreatment. CONCLUSIONS: Childhood maltreatment and history of parental SSD are associated independently with poor early childhood social-emotional functioning, with the impact of exposure to maltreatment on social-emotional functioning in early childhood of greater magnitude than that observed for parental SSDs. The impact of maltreatment was reduced in the context of parental SSDs. The influence of parental SSDs on later outcomes of maltreated children may become more apparent during adolescence and young adulthood when overt symptoms of SSD are likely to emerge. Early intervention to strengthen childhood social-emotional functioning might mitigate the impact of maltreatment, and potentially also avert future psychopathology.

Operationalisation of the European Protocol for Autism Prevalence (EPAP) for Autism Spectrum Disorder Prevalence Measurement in Ireland.

The European Autism Information System project highlighted the lack of systematic and reliable data relating to the prevalence of autism spectrum disorders in Europe. A protocol for the study of ASD prevalence at European level was developed to facilitate a common format for screening and diagnosing children across the EU. This is the first study to operationalise and screen national school children for ASDs using this protocol. National school children 6-11 years (N = 7951) were screened males 54 % (N = 4268) females 46 % (N = 3683). Screening children for ASD implementing the EAIS protocol using the Social Communication Questionnaire (Rutter et al. in Social Communication Questionnaire (SCQ). Western Psychological Services, Los Angeles, ) as a first level screening instrument in a non-clinical setting of Irish national schools was demonstrated.

Ensuring the Health, Safety and Preparedness of U.S. Medical Students Participating in Global Health Electives Overseas.

Global health electives based in resource-poor countries have become extremely popular with medical students from resource rich ones. As the number of such programs and participants increase, so too do the absolute health and safety risks. It is clear from a number of published reports that many institutions provide little or no meaningful preparedness for students and do little to ensure their health and safety. These deficiencies together can affect students, their foreign hosts, and sponsoring institutions. The School of Public Health at the State University of New York, Downstate Medical Center, and its predecessor, the Department of Preventive Medicine and Community Health, have sponsored a 6-8 week global health elective for fourth year medical students since 1980. The purposes of this elective are to provide students with an opportunity to observe the health care and public health systems in resource-poor countries, provide medical service, and have a cross-cultural experience. Over the course of the past 35 years, 386 students have participated in this global health elective in more than 41 resource-poor countries. Recent annual applications for this elective have been as high as 44 out of a class of 200 students. Over the past 10 years, annual acceptance rates have varied, ranging from a low of 32 % in 2007-2008 to a high of 74 % in 2010-2011 and 2013-2014. Careful screening, including a written application, review of academic records and personal interviews, has resulted in the selection of highly mature, adaptable, and dedicated students who have performed well at overseas sites. Appropriately preparing students for an overseas global health experience in resource-poor countries requires the investment of much professional and staff time and effort. At the SUNY Downstate School of Public Health, these resources have underpinned our Global Health in Developing Countries elective for many years. As a result, the elective is characterized by meticulous organization, extensive preparedness measures for students, and continuous monitoring of site and country safety. The health of students is ensured by one-on-one assessment of immunization needs, anti-malarials, and the provision of a five-day supply of post-exposure HIV prophylaxis. Students sign agreements regarding the legal issues, immunizations, and anti-malarials recommended as well as HIV post-exposure prophylaxis. They are also required to obtain medical evacuation insurance provided by the university, and medical care insurance valid overseas. Student travel plans are also approved as is in-country lodging. The focus of our 6-8 week global health elective is not clinical medicine. Rather, it is to enable students to learn about the health care and public health systems in a resource-poor country. Through that focus, they also come to understand the causes of health and health care disparities that exist in the country to which they are assigned. Our students are greatly advantaged with regard to cross-cultural understanding since our school is located in New York City's Borough of Brooklyn, where 40 % of the population was born outside of the U.S. Our comprehensive effort at risk management for this global health elective includes a thorough debriefing for each student upon his/her return. Special attention is given to ascertaining illness or injury while overseas, and, when necessary, immediate referral is made to an appropriate university clinical department where a student can be appropriately case managed. Meticulous oversight, careful selection of safe overseas sites, and attention to preparing students have resulted in significant risk reduction and successful experiences for the majority of our 386 students. This article describes the model we have developed for ensuring the health, safety, and preparedness of students participating in our global health elective.

Folic acid levels in some food staples in Ireland are on the decline: implications for passive folic acid intakes?

BACKGROUND: Neural tube defects are largely preventable by the maternal periconceptual consumption of folic acid. The aim of this study was to examine the levels of synthetic folic acid in foods and the range of food stuffs with added folic acid available to consumers in Ireland at the current time. METHODS: Three audits of fortified foods available in supermarkets in the Republic of Ireland were conducted. Researchers visited supermarkets and obtained folic acid levels from nutrition labels in 2004, 2008 and 2013/4. Levels were compared using MS Excel. RESULTS: The profile of foods fortified with folic acid in 2013/4 has changed since 2004. The percentage of foods fortified with folic acid has decreased as has the level of added folic acid in some food staples, such as fat/dairy spreads. CONCLUSION: Bread, milk and spreads no longer contain as much folic acid as previously (2004 and 2008). This may contribute to a decrease in folate intake and therefore may contribute to an increase in NTD rates. Research on current blood concentrations of folate status markers is now warranted.

Targetable subsets of non-Hodgkin lymphoma in Malawi define therapeutic opportunities.

Diagnostics and supportive care for patients with non-Hodgkin lymphoma (NHL) in lower- and middle-income countries (LMICs) are lacking. We hypothesized that high-throughput transcription-based diagnostics could classify NHL specimens from Malawi amenable to targeted therapeutics. We established tissue microarrays and classified 328 cases diagnosed by hematoxylin and eosin as NHL at University of Malawi College of Medicine using immunohistochemistry (IHC) for conventional markers and therapeutic targets. A subset was analyzed using NanoString-based expression profiling with parsimonious transcriptional classifiers. Overall, 72% of lymphomas were high-grade B-cell tumors, subsets of which were enriched for expression of MYC, BCL2, and/or PD-L1. A 21-gene transcriptional classifier, previously validated in Western cohorts, divided 96% of diffuse large B-cell lymphomas (DLBCLs) with 100% of B-cell lymphomas, unclassifiable, into 1 cluster and 88% of Burkitt lymphomas into a separate cluster. Cell-of-origin categorization of 36 DLBCLs by NanoString lymphoma subtyping test (LST) revealed 69% concordance with IHC. All discordant cases were classified as germinal center B cell-like (GCB) by LST but non-GCB by IHC. In summary, utilization of advanced diagnostics facilitates objective assessment and segregation of biologically defined subsets of NHL from an LMIC without expert review, thereby establishing a basis for the implementation of effective and less toxic targeted agents.

Dentists, antibiotics and Clostridium difficile-associated disease.

Dentists prescribe significant volumes of antimicrobial drugs within primary care settings. There is good evidence that many of the prescriptions are not justified by current clinical guidance and that that there is considerable misuse of these drugs in dentistry. One of the risks associated with antibiotic administration is Clostridium difficile-associated disease (CDAD), an entity of which many healthcare workers, including dentists, have little knowledge or understanding. This review seeks to identify the extent and nature of the problem and provides an up to date summary of current views on CDAD, with particular reference to community acquired disease. As for all healthcare workers, scrupulous attention to standard infection control procedures and reducing inappropriate antibiotic prescribing are essential to reduce the risks of CDAD, prevent emergence of further resistant strains of microorganisms and maintain the value of the arsenal of antibiotics currently available to us.

The Francis Report--implications for oral care of the elderly.

Oral health is an essential, yet often neglected, aspect of care in the elderly population. A mouth free of pain and disease which is functional, comfortable and aesthetic improves quality of life. Following the shocking reports of patient neglect and abuse published in the Francis Report, the dental profession must acknowledge that there are longstanding deficiencies in the provision of oral healthcare for the elderly, whether residing in care homes, hospitals or at home with support. It must be a universal goal to improve the care provision for this population through developing a greater understanding and overcoming the multi-factorial barriers to care. This article will highlight the key features of the Francis Report and its significance in the context of oral healthcare provision for the elderly. Clinical Relevance: To provide insight into the oral healthcare needs of the growing elderly population and the necessity of dealing with the current limitations in service provision.

Environmental endocrine disruptors: Effects on the human male reproductive system.

Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.

Exciton dynamics in carbon nanotubes: from the Luttinger liquid to harmonic oscillators.

We show that the absorption spectrum in semiconducting nanotubes can be determined using the bosonization technique combined with mean-field theory and a harmonic approximation. In this framework, a multiple band semiconducting nanotube reduces to a system of weakly coupled harmonic oscillators. We also find that gaps of any size destroy the Luttinger liquid phase in single-walled carbon nanotubes and give rise to electron density fluctuations that resemble excitons built from quasiparticles. Interband processes, such as multiple exciton generation, become progressively weaker as the length to diameter ratio grows larger.

Differential vasodilation of human placental and myometrial arteries related to myofilament Ca(2+)-desensitization and the expression of Hsp20 but not MYPT1.

Endothelial-dependent regulation of vascular tone occurs in part via protein kinase G1α-mediated changes in smooth muscle myofilament sensitivity to Ca(2+). Tissue-specific differences in PKG-dependent relaxation have been attributed to altered expression of myofilament-associated proteins that are substrates for PKG binding. These include the alternative splicing of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase to yield leucine zipper positive (LZ(+)) and negative (LZ(-)) isovariants, with the former being required for PKG-mediated relaxation, and/or altered expressions of telokin, vasodilator-stimulated phosphoprotein (VASP) or heat shock protein Hsp20. During human pregnancy the uterine and placental circulations remain distinct entities and, as such, their mechanisms of vascular tone regulation may differ. Indeed, the sensitivity of myometrial arteries to endothelial-dependent agonists has been suggested to be greater than that of placental arteries. We tested the hypothesis that this was related to tissue-specific changes in PKG-mediated myofilament Ca(2+)-desensitization and/or the expressions of PKG-interacting myofilament-associated proteins. Permeabilized human placental and myometrial arteries were constricted with maximal activating Ca(2+) (pCa 4.5), or sub-maximal Ca(2+) (pCa 6.7) and the thrombane mimetic U46619, and exposed to 8-Br-cGMP. In each case, relaxation was significantly greater in myometrial arteries (e.g. relaxation in pCa 4.5 to 8-Br-cGMP was 49 ± 9.7%, n = 7) than placental arteries (relaxation of 23 ± 6.6%, n = 6, P < 0.05). MYPT1 protein levels, or MYPT1 LZ(+)/LZ(-) mRNA ratios, were similar for both artery types. Of other proteins examined, only Hsp20 expression was significantly elevated in myometrial arteries than placental arteries. These results demonstrate that the reduced human placental artery relaxation to PKG stimulation lies partly at the level of myofilament (de)activation and may be related to a lower expression of Hsp20 than in myometrial arteries.

Knowledge and use of pre-exposure prophylaxis among an online sample of young men who have sex with men in New York City.

Understanding prior knowledge and experience with pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) is critical to its implementation. In fall 2011, NYC MSM were recruited via banner advertisements on six popular dating websites and asked questions about their knowledge and use of PrEP (n = 329). Overall, 123 (38%) respondents reported knowledge of PrEP, of whom two (1.5%) reported PrEP use in the past 6 months. Knowledge of PrEP was associated with high educational attainment, gay identity and recent HIV testing, suggesting an uneven dissemination of information about PrEP and missed opportunities for education. To avoid disparities in use during scale-up, MSM should be provided with additional information about PrEP.

PGC-1ß mediates adaptive chemoresistance associated with mitochondrial DNA mutations.

Primary mitochondrial dysfunction commonly leads to failure in cellular adaptation to stress. Paradoxically, however, nonsynonymous mutations of mitochondrial DNA (mtDNA) are frequently found in cancer cells and may have a causal role in the development of resistance to genotoxic stress induced by common chemotherapeutic agents, such as cis-diammine-dichloroplatinum(II) (cisplatin, CDDP). Little is known about how these mutations arise and the associated mechanisms leading to chemoresistance. Here, we show that the development of adaptive chemoresistance in the A549 non-small-cell lung cancer cell line to CDDP is associated with the hetero- to homoplasmic shift of a nonsynonymous mutation in MT-ND2, encoding the mitochondrial Complex-I subunit ND2. The mutation resulted in a 50% reduction of the NADH:ubiquinone oxidoreductase activity of the complex, which was compensated by increased biogenesis of respiratory chain complexes. The compensatory mitochondrial biogenesis was most likely mediated by the nuclear co-activators peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) and PGC-1ß, both of which were significantly upregulated in the CDDP-resistant cells. Importantly, both transient and stable silencing of PGC-1ß re-established the sensitivity of these cells to CDDP-induced apoptosis. Remarkably, the PGC-1ß-mediated CDDP resistance was independent of the mitochondrial effects of the co-activator. Altogether, our results suggest that partial respiratory chain defects because of mtDNA mutations can lead to compensatory upregulation of nuclear transcriptional co-regulators, in turn mediating resistance to genotoxic stress.

Genetic screening of Greek patients with Huntington's disease phenocopies identifies an SCA8 expansion.

Huntington's disease (HD) is an autosomal dominant disorder characterized by a triad of chorea, psychiatric disturbance and cognitive decline. Around 1% of patients with HD-like symptoms lack the causative HD expansion and are considered HD phenocopies. Genetic diseases that can present as HD phenocopies include HD-like syndromes such as HDL1, HDL2 and HDL4 (SCA17), some spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA). In this study we screened a cohort of 21 Greek patients with HD phenocopy syndromes formutations causing HDL2, SCA17, SCA1, SCA2, SCA3,SCA8, SCA12 and DRPLA. Fifteen patients (71%) had a positive family history. We identified one patient (4.8% of the total cohort) with an expansion of 81 combined CTA/CTG repeats at the SCA8 locus. This falls within what is believed to be the high-penetrance allele range. In addition to the classic HD triad, the patient had features of dystonia and oculomotor apraxia. There were no cases of HDL2, SCA17, SCA1, SCA2, SCA3, SCA12 or DRPLA. Given the controversy surrounding the SCA8 expansion, the present finding may be incidental. However, if pathogenic, it broadens the phenotype that may be associated with SCA8 expansions. The absence of any other mutations in our cohort is not surprising, given the low probability of reaching a genetic diagnosis in HD phenocopy patients.

The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study.

OBJECTIVE: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1- and 2-year follow-up visits. METHODS: As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count. RESULTS: The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 ± 0.34, second year: 1.44 ± 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females. CONCLUSIONS: Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression.