Polish adaptation of the Dimensional Anhedonia Rating Scale (DARS) - validation in the clinical sample

BackgroundAnhedonia is the core symptom of depression. Its presence has been linked to worsened prognosis. The Dimensional Anhedonia Rating Scale (DARS) is a scale measuring desire, motivation, effort and consummatory pleasure across different domains. The aim of this paper was to confirm factor structure, assess reliability and validity of the Polish adaptation of the DARS in a clinical sample of patients with mood disorders and healthy controls (HC).MethodsThe study sample included 161 participants aged 18–65 years - 34 HC, 72 patients with bipolar disorder and 55 with major depressive disorder (in depressive episode or remission). Reliability of the Polish adaptation of the DARS was assessed using Cronbach’s α and the average inter-item correlation (AIC). Convergent and divergent validity was established by Pearson’s correlations between the DARS and the Snaith-Hamilton Pleasure Scale (SHAPS), the Quick Inventory of Depressive Symptomatology- self-report (QIDS-SR), the Hospital Anxiety and Depression Scale (HADS). The structure of the scale was examined by factor analysis.ResultsThe factor structure was consistent with the original scale. Strong internal consistency for the DARS total score (Cronbach’s α = 0.95) and all subscales (0.86–0.93) was observed. The DARS demonstrated good convergent (moderate to strong correlations with measures of anhedonia and depression) and divergent validity (weak correlations with anxiety level).ConclusionThe Polish DARS demonstrated excellent internal consistency and very good validity. The scale is a valuable contribution to the psychometrics of anhedonia measures in patients with mood disorders

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Data_Sheet_1_Polish adaptation of the Dimensional Anhedonia Rating Scale (DARS) - validation in the clinical sample.docx

BackgroundAnhedonia is the core symptom of depression. Its presence has been linked to worsened prognosis. The Dimensional Anhedonia Rating Scale (DARS) is a scale measuring desire, motivation, effort and consummatory pleasure across different domains. The aim of this paper was to confirm factor structure, assess reliability and validity of the Polish adaptation of the DARS in a clinical sample of patients with mood disorders and healthy controls (HC).MethodsThe study sample included 161 participants aged 18–65 years - 34 HC, 72 patients with bipolar disorder and 55 with major depressive disorder (in depressive episode or remission). Reliability of the Polish adaptation of the DARS was assessed using Cronbach’s α and the average inter-item correlation (AIC). Convergent and divergent validity was established by Pearson’s correlations between the DARS and the Snaith-Hamilton Pleasure Scale (SHAPS), the Quick Inventory of Depressive Symptomatology- self-report (QIDS-SR), the Hospital Anxiety and Depression Scale (HADS). The structure of the scale was examined by factor analysis.ResultsThe factor structure was consistent with the original scale. Strong internal consistency for the DARS total score (Cronbach’s α = 0.95) and all subscales (0.86–0.93) was observed. The DARS demonstrated good convergent (moderate to strong correlations with measures of anhedonia and depression) and divergent validity (weak correlations with anxiety level).ConclusionThe Polish DARS demonstrated excellent internal consistency and very good validity. The scale is a valuable contribution to the psychometrics of anhedonia measures in patients with mood disorders.</p

On the Minimum Number of Multiplications Necessary for Universal Hash Functions

Abstract. Let d ≥ 1 be an integer and R1 be a finite ring whose el-ements are called block. A d-block universal hash over R1 is a vector of d multivariate polynomials in message and key block such that the maximum differential probability of the hash function is “low”. Two such single block hashes are pseudo dot-product (PDP) hash and Bernstein-Rabin-Winograd (BRW) hash which require n 2 multiplications for n mes-sage blocks. The Toeplitz construction and d independent invocations of PDP are d-block hash outputs which require d × n 2 multiplications. How-ever, here we show that at least (d − 1) + n 2 multiplications are necessary to compute a universal hash over n message blocks. We construct a d-block universal hash, called EHC, which requires the matching (d−1)+ n 2 multiplications for d ≤ 4. Hence it is optimum and our lower bound is tight when d ≤ 4. It has similar parllelizibility, key size like Toeplitz and so it can be used as a light-weight universal hash

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589

Optimization of adsorptive removal of α-toluic acid by CaO2 nanoparticles using response surface methodology

The present work addresses the optimization of process parameters for adsorptive removal of α-toluic acid by calcium peroxide (CaO2) nanoparticles using response surface methodology (RSM). CaO2 nanoparticles were synthesized by chemical precipitation method and confirmed by Transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) analysis which shows the CaO2 nanoparticles size range of 5–15 nm. A series of batch adsorption experiments were performed using CaO2 nanoparticles to remove α-toluic acid from the aqueous solution. Further, an experimental based central composite design (CCD) was developed to study the interactive effect of CaO2 adsorbent dosage, initial concentration of α-toluic acid, and contact time on α-toluic acid removal efficiency (response) and optimization of the process. Analysis of variance (ANOVA) was performed to determine the significance of the individual and the interactive effects of variables on the response. The model predicted response showed a good agreement with the experimental response, and the coefficient of determination, (R2) was 0.92. Among the variables, the interactive effect of adsorbent dosage and the initial α-toluic acid concentration was found to have more influence on the response than the contact time. Numerical optimization of process by RSM showed the optimal adsorbent dosage, initial concentration of α-toluic acid, and contact time as 0.03 g, 7.06 g/L, and 34 min respectively. The predicted removal efficiency was 99.50%. The experiments performed under these conditions showed α-toluic acid removal efficiency up to 98.05%, which confirmed the adequacy of the model prediction

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis